19 th Congress of the European Hematology Association

standard protocols. Planar and SPECT images were carried Aggressive Non-Hodgkin - Clinical out 30 minutes and 3 hours after intravenous injection of 740 MBq 99m Tc- Tetrofosmin and analyzed qualitatively and quantitatively. The scintigraphic results were compared with the data of conventional methods (clinical PB1813 examination, x-ray, CT). Additionally, patients underwent 18F-FDG PET-CT scan. Beta-2-microglobulin was measured by radioimmunoassay. THE ROLE OF HIGH DOSE CHEMOTHERAPY FOLLOWED BY Results: 99mTc-Tetrofosmin scintigraphy was positive in 42 patients with HL AUTOLOGOUS STEM CELL TRANSPLANTATION AS FIRST LINE and NHL before treatment. From 58 detected lesions 40 had TREATMENT IN PATIENTS WITH AGGRESSIVE NON-HODGKIN involvement. Increased uptake of the radiotracer was demonstrated in LYMPHOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS mediastinal, neck, supraclavicular, axillar and inguinal lymph nodes. Extranodal D Dahan-Shriki 1, A Gafter-Gvili 1,2, L Vidal 1,2, P Raanani 1,2, O Shpilberg 2, localization was detected in 18 lesions. The tumour/background ratio ranged R Gurion 1,2, * from 1.5 to 2.1. In six patients with false negative scintigraphy, CT investigation 1Institute of Hematology, Rabin Medical Center, Petah Tikva, 2Tel Aviv University, Tel Aviv, Israel showed enlarged abdominal lymph nodes. True negative 99mTc-Tetrofosmin scan after chemotherapy was registered in 37 patients. Focal pathological tetrofosmin uptake was seen in ten patients and 21 lesions were identified. Background: -, , , and (R-CHOP) has been the mainstay of treatment in patients with Fourteen lymph node lesions were detected in mediastinal, neck, aggressive non-Hodgkin lymphoma (NHL). Despite the improvement in survival supraclavicular, axillar and inguinal area. Seven lesions had extranodal rate with the addition of rituximab, there are still a significant proportion of localization – lungs and bones. False negative scintigraphy was found in 8 patients, whereas CT scan showed lesion with subdiaphragmatic localization. patients who cannot be cured with conventional therapy . One of the strategies to improve survival rate is consolidation treatment with high dose chemotherapy The presence of B-symptoms and elevated beta-2-microglobulin were found (HDT) followed by autologous stem cell transplantation (ASCT), especially in in these patients. The patients with inconclusive 99mTc-Tetrofosmin scan were young patients with high risk aggressive NHL. Randomized controlled trials referred to PET-CT. Additional 22 PET-CT positive nodal and extranodal that addressed this issue yielded conflicting results. subdiaphragmatic lesions were detected. 99mTc-Tetrofosmin is a promising tracer in Aims: In order to examine the effect of HDT and ACST on overall survival, we Summary and Conclusions: performed a systematic review and meta-analysis. determining disease activity in supradiaphragmatic lesions. This method that has high sensitivity and low radiation burden, is appropriate in lymphoma Methods: Systematic review and meta-analysis of randomized controlled trials comparing HDT and ASCT after achievement of complete remission (CR) or patients especially with supradiaphragmatic localization of the lesions. In partial remission (PR) to standard dose chemotherapy, with or without rituximab patients with small subdiaphragmatic lesions (<15 mm) and inconclusive as first line treatment in patients with aggressive NHL. The Cochrane Library, 99mTc- Tetrofosmin scintigraphy, PET-CT is method of choice. MEDLINE, conference proceedings and references were searched until December 2013. The primary outcome was overall survival (OS). Secondary outcomes were relapse rate, overall response (ORR), CR and secondary PB1815 malignancies. For dichotomous data, relative risk (RR) with 95% confidence PLUS RITUXIMAB FOR RELAPSED OR REFRACTORY intervals (CIs) were estimated and pooled and hazard ratios (HR) for time to DIFFUSE LARGE LYMPHOMA: A RETROSPECTIVE STUDY event data were estimated and pooled. We used fixed effect model to pool F Merchionne 1,* G Quintana 1, C Minoia 2, A Guarini 2, I Galise 3, G Quarta 1, results. G Loseto 2, A Melpignano 1 Results: Our search yielded 20 trials conducted between the years 1987 and 1Hematology Unit , Ospedale Antonio Perrino , Brindisi, 2Department of Medical 2011, including 4488 patients. In five trials rituximab was added to both arms. and Experimental Oncology, Hematology Unit, IRCCS National Cancer Median age of patients ranged between 31 to 51 years old. Seven trials Research Centre “Giovanni Paolo II”, 3Registro Tumori Puglia, IRCCS National included only patients with intermediate-high and high risk age-adjusted Cancer Research Centre “Giovanni Paolo II”, Bari, Italy international prognostic index (aaIPI). Ten trials were judged to be at low risk for selection bias (allocation concealment and sequence generation).Data from Background: After standard R-CHOP therapy, patients with relapsed or 19 trials were available for analysis of OS. Treatment with HDT and ASCT did refractory diffuse large B cell lymphoma (DLBCL) are generally treated with not improve OS as compared to standard dose chemotherapy, HR 1.09, 95% 2 aggressive salvage chemotherapy followed by high dose therapy with confidence interval (CI) 0.98-1.21, I for heterogeneity 32%. Also, no survival autologous stem-cell transplantation (ASCT). However, for patients who are not benefit was shown in a sub- analysis of patients with intermediate-high and high 2 eligible for intensive and ASCT because of comorbidities aaIPI (HR 1.08 95% CI (0.95-1.24), I =66%, 10 trials). However, HDT and and/or advanced age or relapse after heavy salvage regimens, treatment ASCT was associated with an increased rate of CR [RR 1.07 95% CI (1.02- options are very limited and prognosis is poor. Based on the demonstration of 1.11)], and a decreased rate of relapse, RR 0.58 95% CI (0.49-0.69). No efficacy and safety of bendamustine plus rituximab (BR) in patients with indolent statistically significant difference was observed regarding the incidence of and mantle cell non-Hodgkin in terms of increased progression-free secondary malignancies. survival and fewer toxic effects than R-CHOP, additional studies are being HDT and ASCT as first line treatment for Summary and Conclusions: carried out to assess the activity and safety of this combination in patients with aggressive NHL is not associated with increased OS, yet it improves CR rate DLBCL not eligible for intensive chemotherapy regimens. and decreases relapse rate. The possibility to salvage relapsing patients with Aims: To analyze a group of patients with relapsed or refractory DLBCL treated HDT and ASCT may contribute to the lack of effect of this treatment on OS when with combination BR between July 2010 and January 2014, and to evaluate given as first line therapy. overall response rate (ORR), progression-free survival (PFS) and treatment safety. Methods: Of 22 patients registered, 19 (14 males and 5 females) are currently PB1814 available for this analysis. Patients gave informed consent. The median age USEFULNESS OF 99M TC-TETROFOSMIN SCINTIGRAPHY IN THE was 71 years (range 54-82); ECOG performance status was 1 (n=6, 27.2%), FOLLOW UP IN PATIENTS WITH MALIGNANT LYMPHOMA IN THE ERA OF 2 (n=15, 68.1%) and 3 (n=1, 4.5%); R-IPI scores before starting therapy were 18F-FDG PET-CT good (n=13, 59%) and poor (n=9, 41%). The median number of prior D Vassileva 1,* B Spassov 2, S Sergieva 3, M Garcheva 4, I Kostadinova 4 chemotherapy regimens was 2 (range 1-5); lactate dehydrogenase was 1Nuclear Medicine, 2Clinical hematology, NSBALHZ, 3Cancer Center, 4Nuclear elevated in 12 patients (54.5%) and normal in 10 (45.4%). The Ann Arbor Medicine, University Hospital Alexandrovska, Sofia, Bulgaria clinical stage at baseline was IV (n=8, 36.3%), III (n=8, 36.3%), and II (n=6, 27.2%). Rituximab was administered at the standard dose of 375 mg/m 2 and Background: In patients with malignant lymphomas the precise staging and bendamustine at a dose between 70 and 120 mg/m 2 (mean 90 mg/m 2) on days follow up is very important for treatment and prognosis of these patients. 1 and 2 of each 28-day cycle for up to six cycles. Nine patients (41%) completed 99mTc-Tetrofosmin is currently used to study myocardial perfusion, but also has six cycles of treatment and the median number of cycles received per patient been reported to be localized in various types of malignant tumours, including was 5 (range 1-6). lymphomas, giving their localization and proliferation activity. With previously Results: ORR was 47.3% (complete response: n=7 patients, 36.8% and partial used visualized techniques it has been extremely difficult to differentiate response: n=2 patients, 10.5%), with stable disease in 1 patient (5.2%) and metabolically active tumour tissue from post-therapy fibrosis. Nowadays 18F- progression disease in 9 patients (47.3%). At the median follow up of 6.4 FDG PET-CT is a method of choice for these applications. months (range 1 to 37.4 months), the median PFS was 7 months (95% CI 4.4 Aims: In this study, we aimed to evaluate the role of 99mTc-Tetrofosmin - 26.6) for all patients. Four patients showed remission lasting longer than 24 scintigraphy for therapy control of lymphoma patients in the era of 18F-FDG months. Grade 3 / 4 toxicities observed were: lymphopenia (42.1%), PET-CT. neutropenia (36.8%), anemia (15.7%), and thrombocytopenia (10.5%). Methods: We investigated 103 patients (56 men and 47 women) with Hodgkin’s Infection by cytomegalovirus (CMV) was observed in two patients (10.5%). (HL) and non-Hodgkin’s lymphoma (NHL), aged 19-73 years and treated with Common non-hematologic adverse events included nausea (31.5%), fever

698 | haematologica | 2014; 99(s1) Milan, Italy, June 12 – 15, 2014

(21%), fatigue (15.7%), cutaneous rash (5.2%), and diarrhoea (5.2%). One Methods: A literature search was conducted for randomized controlled trials patient experienced transfusion-dependent anemia one year after the end of and observational studies of Z-BEAM as a conditioning regimen for ASCT in therapy, and a diagnosis of myelodysplastic syndrome refractory anemia type adult patients with DLBCL. Extracted data included baseline patient was made. demographics, overall response (ORR), complete response (CR), overall Summary and Conclusions: BR can be considered to have a role in the survival (OS), progression-free survival (PFS), non-relapse mortality (NRM), treatment of patients with relapsed/refractory DLBCL with limited therapeutic median time to ANC and platelet engraftment, and rate of myelodysplastic options, in that it can induce long-term remission in some patients with an syndrome. Mixed effects models were used to determine estimates. acceptable toxicity profile. However, the high percentage of non-responding Results: Twelve studies (N = 409) were included in the meta-analysis. The 2- patients in this study suggests that larger trials are needed to assess the efficacy year OS and PFS were 85.5% (n=409) and 67.7% (n=366), respectively. of this combination. Outcomes were superior in patients with non-transformed lymphoma. Post- Disclosures: Off Label Use: bendamustine in salvage therapy in aggressive transplant, ORR and CR rates were 72.6% and 68.5%, respectively. The B-cell NHL. primary toxicity was neutropenia (49.9%). Two-year OS was significantly associated with pre-transplant ORR (p=0.002, tau square=0) and with pre- transplant CR rate (p=0.04, tau square=0.15). There was no significant PB1816 association between PFS and pre-transplant response. Summary and Conclusions: Z-BEAM is safe and effective as a conditioning Abstract withdrawn regimen in relapsed/refractory DLBCL.

PB1817 PB1819 ASSOCIATION OF POLYMORPHISM RS1625895 GENE TP53 WITH GOOD PROGNOSIS OF PATIENTS WITH PRIMARY INTRAOCULAR EFFECTIVENESS OF R-CHOP TREATMENT OF DLBCL LYMPHOMA TREATED WITH SYSTEMIC HIGH DOSE 1 * 2 1 1 2 E Voropaeva , T Pospelova , M Voevoda , V Maximov , O Berezina AND INTRAVITREAL METHOTREXATE INJECTION: A STUDY OF 23 1 Scientific Research Institute of Therapy, The Russian Academy of Medical PATIENTS 2 Science, Novosibirsk State Medical University, Novosibirsk, Russian WL Ma 1,* YK Chen 2, HA Hou 2, JL Tang 2, W Tsay 2, CP Lin 3, HF Tien 2 Federation 1Division of Hematology, Department of Internal Medicine, Department of Oncology, 2Division of Hematology, Department of Internal Medicine, Background: In response to DNA damage the p53 protein functions to induce 3Department of Ophthalmology, National Taiwan University Hospital, Taipei, arrest, DNA repair or apoptosis. Deficiency of p53 function is one of Taiwan, Republic of China the adverse prognostic factors in NHL. In DLBCL incidence of TP53 mutations and 17p deletion in the onset of the disease is rare. Peller et al. (1997) described Background: Primary intraocular lymphoma (PIOL) is a rare subtype of rs1625895 gene TP53 associated with changes in apoptosis of leukocytes in malignant non-Hodgkin’s lymphoma which occurs either alone or in association patients with cancers. with brain involvement. Diagnosis of PIOL can be challenging and the optimal Aims: The purpose of the present study was study association of rs1625895 treatment has yet to be defined. with with effectiveness of R-CHOP treatment of DLBCL. Aims: This study is to assess the clinic-biologic features, diagnostic tools and Methods: We studied the single nucleotide polymorphism rs1625895 in 106 treatment outcome in a cohort of patients with PIOL. unrelated patients with DLBCL treated by R-CHOP. Clinical response to Methods: Retrospective case analysis of medical records and review of treatment was assessed according to Cheson Criteria. Genotyping was carried cytology of a consecutive series of 23 patients presenting with PIOL who out with use of PCR-RFLP. Overall survival (OS) and relapse-free survival were treated with systemic high dose methotrexate and intravitreal (RFS) probabilities were estimated with the use of the Kaplan–Meier method methotrexate injection at the National Taiwan University Hospital between and were compared between patients with a mutation and those without mutant Jan 2003 and Jul 2013 were investigated. Clinical data, including patient’s age alleles by means of the log-rank test. Multivariate analyses were conducted with at the onset of disease, gender, medical history, clinical findings, laboratory the use of the Cox model with forward selection to identify independent investigations, mode of diagnosis, interval between the onset of symptoms prognostic variables influencing the OS and RFS. and final diagnosis, type of therapy, disease course and duration of survival Results: For rs1625895 genotype distribution in DLBCL patients was as were obtained. follows: genotype G/G - 75,5%, G/A - 22.6% and A/A - 1.9%. Results: Of 23 patients enrolled, 17 (73.9%) were female. The median age The response rate in subgroups of patients with rare allele and homozygous of onset of symptoms was 64.5 years with range from 36 to 76 years. All the genotype G/G was 73.1% and 50.0%, respectively (p=0.0396). Odds ratio patients were immune-competent and human immunodeficiency response to R-CHOP therapy in patients with genotype G/G, was 0.37 [95% negative. The commonest symptoms reported by patients were blurred and/or CI: 0,15; 0,99, P <0,05]. In patients with DLBCL with genotype G/G rs1625895 floaters. The diagnosis of PIOL of these patients was based on the 5 - year OS was 42.5% vs 65.4% in patients with genotypes G/A and A/A (p identification of abnormal lymphoid cells in vitreous fluid and 6 patients =0.014). In the subgroup of patients with homozygous genotype G/G (26.1%) had bilateral eye involvement. The median time from the initial ocular rs1625895 relapse-free survival was 36.3%. It was significantly lower presentation to diagnosis was 6 months (range 1.6–26.6 months). Eight (p=0.030) than in the subgroup of patients with genotypes G/A and A/A - patients had concurrent brain involvement at diagnosis, including three 57.7%. In multivariate analysis by Cox regression method was shown that patients with parenchyma lesions. None had systemic involvement. Among rs1625895, along with the index IPI, can serve as a predictor of the likelihood 15 patients receiving examination, all patients were diagnosed of achieving OS and DFS. as having B-cell lymphoma with monoclonality of light chain. All patients Summary and Conclusions: The present study showed that genotype G/G received both systemic chemotherapy with high-dose methotrexate (MTx, 8 2 rs1625895 gene TP53 is associated with a high probability of failure R-CHOP gm/m on day 1) and intravitreal injection with MTx as the induction regimen. therapy of DLBCL patients. Future studies to confirm these data are required. Nineteen patients (79.2%) achieved first complete remission (CR1) with a median interval of three months. Among them, eight (42.1%) relapsed with a median remission duration of 7.8 months (range 2.8-21.4). Fortunately, seven PB1818 (87.5%) patients achieved second CR after salvage chemotherapy with intravitreal MTx, systemic BOMES (BCNU 65 mg/m 2 on day 1 and day 2, OUTCOMES AFTER 90YTTRIUM-IBRITUMOMAB TIUXETAN-BEAM IN oncovin 2 mg on day 1 and day 8, methotrexate 1.5 gm/m 2 on day 8, DIFFUSE LARGE B-CELL LYMPHOMA: A META-ANALYSIS 50 mg/m 2 on days 1-5 and methylprednisolone 200 mg on days 1- S Auger 1,* Y Duny 2, JP Daures 2, P Quittet 3 7) or whole brain radiotherapy. The most common adverse effects of high- 1Internal médicine and hematology, ClinicBeausoleil, 2Biostatistical and dose MTx were manageable and reversible, including hepatotoxicity (grade Epidemiology, INSERM Unit EA 2415, 3Hematology, University hospital, I, 9 patients; grade II, 6 and grade III, 6) and nephrotoxicity (grade I, 2 and Montpellier, France grade II, 2). With a median follow-up duration of 81.8 months (range 4.4- 117.3) the five-year overall survival (OS) rate was 64.7% and the median OS Background: High-dose chemotherapy followed by autologous stem cell was not reached. A total of 5 patients died of lymphoma (21.7%). There was transplantation (ASCT) is a standard therapy in patients with relapsed/refractory no survival difference between the patients with and without CNS diffuse large B-cell lymphoma (DLBCL) who are chemo-sensitive. The involvement. combination of , etoposide, , and (BEAM) is Summary and Conclusions: Diagnosis of PIOL requires both clinical suspicion commonly used as a conditioning regimen. The addition of yttrium-90 ( 90 Y)- and careful cytologic examination. The frontline treatment with high-dose MTx ibritumomab tiuxetan (Zevalin®) to BEAM (Z-BEAM) is increasingly being used and intravitreal chemotherapy yielded a substantial remission rate and longer to improve outcomes and overcome refractory disease. survival. It is proved to be an effective regimen with manageable side effects. Aims: We conducted a literature review and meta-analysis in order to evaluate the clinical effects of Z-BEAM followed by ASCT in patients with DLBCL

haematologica | 2014; 99(s1) | 699 19 th Congress of the European Hematology Association

PB1820 receptor repertoire to identify source-specific thresholds that differentiate high- frequency clones from neoplastic clones. EFFICACY AND TOXICITY OF MOGAMULIZUMAB FOR RELAPLSED/ Methods: We developed a method that amplifies rearranged antigen receptor REFRACTORY ADULT T-CELL -LYMPHOMA: A RETEOSPECTI- CDR3 sequences and uses high-throughput sequencing (HTS) to sequence VE ANALYSIS IN SAGA PREFECTURE, JAPAN tens of thousands of chains simultaneously. Because the technology utilizes K Kamachi 1,* Y Kubota 1, H Ureshino 2, M Miyahara 2, M Yoshihara 1, H Kitamura 1, 1 1 1 1 3 1 gDNA the frequency of sequenced CDR3 chains is representative of the relative M Ide , T Shindo , T Ando , K Kojima , E Sueoka , S Kimuira frequency of each CDR3 sequence in the sample population of lymphocytes. 1Department of Internal Medicine, Saga University, Saga, 2Department of 3 To demonstrate the potential of HTS of T and B-cell receptors to contribute to Internal Medicine, Karatsu Red Cross Hospital, Karatsu, Department of diagnosing and monitoring neoplasia in mature lymphomas; we amplify the Clinical Laboratory Medicine, Saga University, Saga, Japan TCR repertoire of 98 and the BCR repertoire of 60 index samples to identify high-frequency TRB or IGH rearrangements. Concurrently, we sequence the Background: Adult T-cell leukemia-lymphoma (ATL) is an aggressive TRB and IGH repertoire in control blood, bone marrow, skin, and reactive lymph peripheral T-cell caused by human T-cell lymphotropic virus type I, tissue from 7, 8, 6, and 14 samples respectively. Clones in the index samples and incurable by conventional chometherapy. CC chemokine receptor 4 are classified as neoplastic if occurring at a proportion greater than 7 standard (CCR4) is a chemokine receptor expressed on T-helper type 2 and regulatory deviations above the mean frequency of the most abundant rearranged TRB T cells (Treg). CCR4 is also expressed on tumor cells from about 90% of or IGH in matched control samples. patients with ATL. Mogamulizumab is a defucosylated humanized anti-CCR4 Results: Using control samples, we defined the expected frequency of highest- that show potent antibody-dependent cell cytotoxicity (ADCC). In the copy clones by source type (Table 1). Using our definition of neoplastic clone, phase II study, mogamulizumab has been shown to be effective and well Eighty-four percent of our 158 index samples have a tractable rearrangement. tolerated against relapsed ATL patients. However, its efficacy and toxicity has not been evaluated in clinical practice. Aims: We investigated and analyzed the efficacy and toxicity of 20 patients with Table 1. Average and standard deviation of highest copy TCR clones in relapsed/refractory ATL. control samples. Methods: Relapsed or refractory ATL patients treated with mogamulizumab at Saga University Hospital and Karatsu Red Cross Hospital from April 2012 to December 2013, were evaluated. Overall survival (OS) was analyzed from the date of the first dose to death or to date of last follow-up. Results: A total of 20 patients (13 male, 7 female) was evaluated. Median age was 70 years (range, 46-84). The disease subtypes at initial therapy included 17 acute, 2 lymphoma, 1 unfavorable chronic type ATL. The responses to prior therapy were 1 CR, 5 PR, 4 SD, and 10 PD. We find that for most disease diagnoses, high- Mogamulizumab was intravenously administered once a week for 8 weeks Summary and Conclusions: throughput sequencing identifies a tractable clone and T-cell and B-cell receptor at a dose of 1.0mg/kg, and 5 patients (25%) completed the schedule. Of the repertoire analysis may be useful for clinical laboratory evaluation of patients remaining 15 patients, 9 discontinued treatment because of disease with T and B-cell . progression, 1 because of skin rash, and 5 because of others. The median number of mogamulizumab infusion was 4 (range, 1-8). Eight of the 20 patients (40%) achieved objective response, including 4 with CR (20%) and 4 (20%) with PR. The response in the remaining12 patients was SD in 2 PB1823 patients (10%) and PD in 10 patients (50%). Response rate for relapsed ATL NUMBER NEEDED TO TREAT AND COST UTILITY ANALYSIS OF and refractory ATL was 17% (1 in 6 patients), and 50% (7 in 14 patients), GRANULOCYTE-COLONY STIMULATING FACTORS FOR PRIMARY respectively. Responses according to disease site were 88% (of 17 patients, PROPHYLAXIS OF CHEMOTHERAPY INDUCED FEBRILE NEUTROPENIA 12 CR and 3 PR) for peripheral blood, 38% (of 8 patients, 3 PR) for skin, and IN DLBCL PATIENTS IN THE NETHERLANDS 27% (of 15 patients, 1 CR and 3 PR) for nodal lesions. Median OS were 5 E Lugtenburg 1,* MD Levin 2, L Somers 3 months (range, 0.3-16.2). Adverse events at grades 3 to 4 were 8 1Hematology, Erasmus MC Cancer Institute, Rotterdam, 2Hematology, Albert lymphopenia (40%), 2 skin rash (10%), and 1 thrombocytopenia (5%). Schweitzer Hospital , Dordrecht, Netherlands, 3OncoLogX, Antwerpen, Belgium Summary and Conclusions: In the present study, mogamulizumab showed efficacy similar to that shown in the phase II study for refractory ATL patients, Background: Myelosuppression is a frequent side effect of (R)CHOP however, the response rate for relapsed ATL patients was low. OS was also chemotherapy. Severe neutropenia can leave patients vulnerable to febrile shorter than that of the phase II study. Further clinical investigations are neutropenia (FN), with associated in-hospital mortality rates in non-Hodgkin’s required to examine whether concomitant use of this novel agent with other Lymphoma (NHL) of up to 9.4%. Severe neutropenia and FN also have the drugs with different mechanism of action would be more effective for ATLs. potential to delay chemotherapy cycles and mandate dose reductions. Though allogeneic hematopoietic cell transplantation (allo-HCT) is a promising Compromising the relative dose intensity of (R)CHOP-21 chemotherapy may treatment to achieve long-term survival for patients with relapsed or refractory result in poorer survival outcomes in diffuse large B-cell lymphoma (DLBCL). ATL, mogamulizumab may be the good option for those who are ineligible for International guidelines by EORTC, ESMO, ASCO and NCCN recommend allo-HCT. In the congress, we will also discuss about the effect of using granulocyte-colony stimulating factor (G-CSF) for primary prophylaxis mogamulizumab for graft- versus -host disease after allo-HCT. (PP) to reduce the incidence of febrile neutropenia (FN) for patients at an overall FN risk of 20% or more. For adult patients with NHL treated with (R)CHOP-21 like chemotherapy, FN incidences between 17% and 50% have PB1821 been reported, demonstrating the eligibility of this regimen for PP with G-CSF as indicated in international guidelines. Abstract withdrawn Aims: 1.To estimate the number needed to treat (NNT) to avoid an FN episode for different PP options in comparison to no prophylaxis in patients receiving 6 cycles of standard (R)CHOP-21 chemotherapy for DLBCL. 2. To assess the PB1822 cost-utility in the Netherlands of PP with once-per-cycle pegfilgrastim compared IDENTIFYING LYMPHOMA ANTIGEN RECEPTOR SEQUENCES BY to no prophylaxis, PP with daily filgrastim (11- or 6-days per cycle) and IMMUNE REPERTOIRE PROFILING secondary prophylaxis (SP) with pegfilgrastim. A Sherwood 1, H Robins 2,*JR Fromm 3, HA Greisman 3, DE Sabath 3, R Emerson 1, Methods: A decision-analytic model was constructed from the Dutch healthcare- M Rieder 1, BL Wood 3, D Wu 3 payer perspective. Costs were obtained from official list prices (January 2014) or 1Adaptive Biotechnologies, 2Fred Hutchinson Cancer Research Center, literature and included drugs (lowest list prices for each product), drug 3University of Washington, Seattle, United States administration and FN-related hospitalization costs. G-CSF relative effectiveness inputs were based on a recent meta-analysis and previous NHL studies. Survival Background: Neoplastic T and B cells rapidly expand, leading to T and B-cell and utility variables were modeled from available data for NHL patients in the US receptor (TCR and BCR) repertoires dominated by one rearrangement. SEER cancer registry and published literature. Univariate sensitivity analyses Techniques that use amplification of rearranged receptors from unselected evaluated the robustness of the model for all input variables. population s of lymphocytes to identify malignancy, including high-throughput Results: PP with pegfilgrastim provides the most effective primary sequencing and the biomed primers, assume that neoplastic clones are present prophylaxis of FN with a NNT to avoid an FN episode of 4.7 (see Table 1). In at conspicuously high frequency. However clones reacting to an antigen also the cost-utility analysis PP with pegfilgrastim was dominant (more effective expand. Differentiating high-frequency reactive clones from lymphomas is and cost saving) compared to PP with 11-days filgrastim and cost-effective important for both diagnosing and monitoring lymphomas. compared to no prophylaxis, PP with 6-days filgrastim and SP with Aims: This project aims to use high-throughput sequencing of the antigen pegfilgrastim. (see Table 2) The sensitivity analyses revealed that baseline

700 | haematologica | 2014; 99(s1) Milan, Italy, June 12 – 15, 2014

FN risk, G-CSF effectiveness in reducing FN and long term survival Vincent’s Hospital, College of Medicine, Catholic University of Korea, assumptions were the most sensitive parameters, and showed that the model 4Department of Internal Medicine, St. VIncnet’s Hospital, College of Medicine was robust. Even when in a scenario analysis the price of daily G-CSF was Catholic University of Korea, 5Department of Radiology, St. Vincent’s Hospital, reduced by up to 90%, PP with pegfilgrastim remained cost-effective College of Medicine Catholic University of Korea, Suwon, 6Department of compared to the daily G-CSF options. Nursing, Wonkwang University, Iksan, 7Department of Internal Medicine, Chonbuk National Unviersity Hospital, Jeonju, Korea, Republic Of

Table 1. Number needed to treat to avoid an FN episode. Background: Interim positron emission tomography (PET) scan has been found to be effective in Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL). The prognostic value of interim PET in mature T-cell and NK-cell lymphoma remains uncertain. Recently, the Deauville five-point scale (5-PS), which visually assess the uptake of lesions in comparison with background mediastinal and liver uptakes, has been validated in the large numbers of patients with HL and DLBCL. However, the prognostic impact of 5-PS on clinical outcomes has not been investigated in mature T-cell and NK-cell lymphoma. Table 2. Cost utility of PP pegfilgrastim in comparison to other strategies. Aims: The aim of this study was to determine the prognostic role of interim PET, assessed by Deauville 5-PS, in patients with mature T cell and NK cell lymphoma and treated with systemic chemotherapy. Methods: We consecutively enrolled patients with newly diagnosed mature T-cell and NK-cell lymphoma, treated with CHOP/CHOP-like or non-- based chemotherapy and had the baseline PET data with ³1 evaluable hypermetabolic lesion between 2006 and 2012 in two Korean institutions. Patients treated with upfront chemoradiotherapy before interim PET scan were excluded. Interim PET scan was performed after 3 cycles of chemotherapy, before 1 week of the next cycle. Interim PET response was visually assessed by 5-PS and four point or higher was regarded as positive. All PET assessment was performed by 2 nuclear medicine specialists at each institution, and the discrepancy of assessment was resolved by the agreement through discussion. Results: A total of 35 patients was included in this analysis. The median age was 60 years (range, 31-79) and 26 (74%) were male. Histologic subtypes Summary and Conclusions: For DLBCL patients treated with (R)CHOP in the included were PTCL, not otherwise specified in 10 (29%), extranodal NK/T cell Netherlands, primary prophylaxis of FN with pegfilgrastim is a cost-effective use lymphoma in 8 (23%), angioimmunoblastic T cell lymphoma in 7 (20%), of healthcare resources. anaplastic large cell lymphoma, ALK negative in 4 (11%), and others in 6 (18%). 22 patients (63%) were presented as advanced stage disease and 9 (26%) had B symptoms. ECOG performance status was ≥ 2 in 7 (20%), serum LDH level PB1824 was elevated in 16 (46%), and bone marrow was involved in 5 (14%). Thus, 14 patients (40%) were classified as high risk (≥ 2 factors) by the prognostic index HIGH-DOSE METHOTREXATE, HIGH-DOSE CYTARABINE AND for PTCL (PIT). 31 patients (89%) completed planned systemic FOR THE TREATMENT OF PRIMARY CENTRAL chemotherapy±involved-field radiotherapy and 25 (71%) achieved complete NERVOUS SYSTEM LYMPHOMA (PCNSL), SIX YEARS SURVIVAL IS response by systemic chemotherapy. 10 patients (29%) underwent REACHED M Salamoon 1,2, *M kenj 3 consolidative autologous stem cell transplantation (ASCT). Using 5-PS, interim 1medical oncology, 2hematology, al Bairouni university hospital, 3cytogenetics, PET scan was visually scored as follows; 1 point in 10 patients (29%), 2 in 6 kenj labs, damascus, Syrian Arab Republic (17%), 3 in 8 (23%), 4 in 7 (20%), and 5 in 4 (11%). Among these, 11 patients (31%) had 4 point or above were considered positive for interim PET scan. Background: Treatment of primary central nervous system lymphoma With a median follow-up of 43.4 (range, 4.3-89.8) months, progression-free (PCNSL) associates with low response rates and poor survival using survival (PFS; median, 5.2 vs 38.0 months, respectively; P=0.001) and overall conventional radio and chemotherapy. Due to its favorable toxicity profile, survival (median, 12.6 months vs not reached, respectively; P=0.004) was Temozolomide has emerged as a new option for treatment of PCNSL in young significantly worse in patients with positive interim PET than those with negative patients. In this study we report a series of (PCNSL) patients treated with an results. In multivariate analysis for PFS, high risk of PIT (HR, 3.67; 95% CI, 1.13- innovative regimen. 11.99) and positive interim PET (HR, 4.02; 95% CI, 1.32-12.23) were Aims: To evaluate a new intensive chemotherapy with Temozolomide, trying to independently associated with faster disease progression. assess response and progression free survival and overall survival taking into Summary and Conclusions: This study represents that Deauville 5-PS is consideration the toxicity profile. The study was performed at Al Mowassa useful to predict early outcomes of patients with mature T-cell and NK-cell Charity hospital in Damascus (SYRIA). lymphoma. Patients with positive interim PET are associated with extremely Methods: 40 patients with histologically confirmed PCNSL median age 52 poor early outcomes. Further studies regarding response-adapted stratification years (range 20-65) years were included. Biopsies were cultured and a based on interim PET might be needed in mature T-cell and NK-cell lymphoma. Karyotyping was made in 32 patients. An induction chemotherapy was started Methotrexate 3 gr/m² over 12 hours on day1 , Cytarabine 3 gr/m² every 12 hours on day 1 and Temozolomide 150 mg/m² from day 2 through day 6 with a PB1826 total of 6 cycles were given on a monthly basis. SIMILAR PROGNOSIS OF TRANSFORMED AND DE NOVO DIFFUSE Results: Among the 40 patients included in the study a complete response was observed in 34 patients (85%) and a partial response in the remaining 6 patients LARGE B CELL LYMPHOMA TREATED WITH IMMUNOCHEMOTHERAPY M Sorigue 1,* O Garcia 2, MJ Baptista 3, G Tapia 4, JM Sancho 5, J L Mate 4, (15%). Disease progressed in 8 out of 40 patients (20%) while 32 patients are J Juncà 5, F Millà 5, E Feliu 5, JM Ribera 5, JT Navarro 5 still living at five years making the overall survival reaching (80%). Grade II 1Department of Hematology, ICO-Hospital Germans Trias i Pujol, 2Department nephrotoxicity was observed in 2 patients while grade III and IV hematotoxicity of Hematology, ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia was observed in 5 patients. The study was updated in January 2014 and we Research Institute, 3Josep Carreras Leukemia Research Institute , 4Department still have the same progression free survival but we lost a patient died from heart of Pathology, Hospital Germans Trias i Pujol, Universitat Autonoma de attack making the overall survival rate 77% at 6 years. Barcelona, 5Department of Hematology, ICO-Hospital Germans Trias i Pujol, Summary and Conclusions: high-dose of both Ara-c and MTX combined with Josep Carreras Leukemia Research Institute. Universitat Autónoma de Temozolomide appears to be a good choice in the treatment of PCNSL, in the Barcelona, Badalona, Spain light of good response and overall survival rates Background: Transformed diffuse large B cell lymphomas (TL) have historically been associated with an aggressive course and a poor prognosis. However, in PB1825 the last decade some studies have shown an important improvement in their PROGNOSTIC SIGNIFICANCE OF INTERIM POSITRON EMISSION prognosis. Furthermore, diffuse large B cell lymphomas (DLBCL) are TOMOGRAPHY SCAN IN PATIENTS WITH MATURE T-CELL AND NK-CELL heterogeneous, with major groups defined by the cell of origin (COO). There are LYMPHOMA few studies aiming to characterize the COO in TL and its prognostic implications. HY Yhim 1,* NR Lee 1, EK Song 1, SY Jeon 1, CY Yim 1, YH Han 2, MH Sohn 2, Aims: To compare the clinical and biological features (including the COO), as B Lee 3, JA Kim 4, YH Park 5, WH Choi 5, HS Kim 6, JY Kwak 7 well as the prognosis between TL and DLBCL treated with rituximab and 1Department of Internal Medicine, 2Department of Nuclear Medicine, Chonbuk chemotherapy. National University Hospital, Jeonju, 3Department of Internal Medicine, St. Methods: We revised the records of 163 patients with DLBCL with those from

haematologica | 2014; 99(s1) | 701 19 th Congress of the European Hematology Association

31 with TL treated between 2003 and 2012 in our institution. The COO was Y Zeng 1,7 , Z Xiao 1,8 , Y Liang 1,9 , Y Zhuang 2, 0J Wang 2, 1Z Sun 2, 2H Bai 2,3 , established by the Hans’ algorythm, which uses the imunohistochemical T Cui 2,4 , J Feng 1 expression of CD10, BCL6 and MUM1 on tissue sections to classify DLBCL into 1Jiangsu Cancer Hospital, Nanjing, 2Henan Cancer Hospital, Zhengzhou, germinal center B-cell like (GCB) and non-GCB. Only patients diagnosed by 3Shanxi Cancer Hospital, Taiyuan, 4The First Affiliated Hospital of Zhengzhou tissue biopsy were included. Patients not treated with immunochemotherapy, University, Zhengzhou, 5Jilin University First Affiliated Hospital, Changchun, HIV positive, those whose biopsy specimen was unavailable for revision and 6Union Hospital Tongji Medical College Huazhong University of Science and those with specific subtypes of DLBCL such as primary cutaneous DLBCL, leg Technology, Wuhan, 7The Second Affiliated Hospital of Zhejiang University type and primary mediastinal DLBCL were excluded from the study. School of Medicine, Hangzhou, 8Fourth Hospital of Hebei Medical University, Results: 29 patients with TL and 101 with DLBCL were included in the study. Of Shijiazhuang, 9Affiliated Hospital of Shandong Academy of Medical Sciences, the 29 TL, 9 had a previous diagnosis of follicular lymphoma (FL), 6 of marginal Jinan, 10 Nanfang Medical University Nanfang Hospital, Guangzhou, zone lymphoma, 4 chronic lymphocytic leukemia (CLL) and 10 showed both 11 Guangdong Foshan First Hospital, Foshan, 12 Guangdong Zhongshan People’s DLBCL and FL in the same lymph node (composite lymphoma). There were no Hospital, Zhongshan, 13 Fuzhou General Hospital of Nanjing Military Command, differences in the clinical or analytical parameters between TL and DLBCL. TL Fuzhou, 14 Xiangya Hospital Central South University, Changsha, 15 Changzhou was diagnosed at advanced stages in 68% of cases while DLBCL was in 53% First People’s Hospital, Changzhou, 16 307 Hospital of PLA, Beijing, 17 First (p=0.198). Data on the COO was available for 23 TL and 76 DLBCL. All TL Affiliated Hospital of Kunming Medical University, Kunming, 18 Affiliated Hospital evolving from FL (7/7) and composite lymphomas (9/9) were GCB while all TL of Nei Mongol Medical College, Hohhot, 19 The Fourth Military Medical University from marginal lymphoma (4/4) and CLL (3/3) were non-GCB. Overall, 16 out of Affiliated Tangdu Hospital, Xi’an, 20 Daqing General Hospital Group Oilfield 23 (70%) were GCB. 32 out of 76 (42%) DLBCL were CGB. TL were more General Hospital, Daqing, 21 Affiliated Hospital of Guiyang Medical College, frequently of GCB subtype than DLBCL (p=0.031) and CD10 was expressed Guiyang, 22 Anhui Provincial Hospital, Hefei, 23 Lanzhou Military Hospital, more frequently in TL (p=0.002). TL and DLBCL were treated with RCHOP in 21 Lanzhou, 24 Fujian provincial hospital, Fuzhou, China and 89 cases, respectively. Five TL cases received consolidation with autologous stem cell transplantation (SCT) in first remission and 2 were submitted to Background: HBV infection is highly prevalent in Chinese patients (pts) with B- allogeneic SCT. No DLBCL patient received SCT in first remission. There were NHL, compared with the general population. Rituximab (R) and chemotherapy no differences between TL and DLBCL in the rate of complete remission with first (chemo) have been associated with HBV reactivation, which may influence the line treatment (62% vs. 66%), nor in overall survival (OS, 63%, [95%CI 43%,83%] continuation of therapy and can result in fatal liver dysfunction. Therefore, vs. 61% [95%CI 50%,72%]), or in progression-free survival (PFS, 61% [95%CI standardized management of HBV reactivation in pts receiving chemo is needed. 42%,80%] vs. 60% [95%CI 49%,71%] respectively). Excluding the 7 patients Aims: To describe the management status of B-NHL pts with HBV infections with TL who received SCT, the OS and PFS in TL treated only with in real practice in China. immunochemotherapy were 58% (95%CI 35%,81%) and 55% (95%CI Methods: Pts with previously untreated DLBCL and FL who were eligible to 33%,77%), respectively, without differences with those observed in DLBCL receive R-chemo were enrolled in a multicenter, prospective, single-arm patients. Analyzing only GCB lymphomas, there were no differences between TL observational study in China. Data were collected and analyzed from medical and DLBCL in both OS (61% vs. 62%) and PFS (66% vs. 63%). records 120 d after the last R dose was administered. HBV infection Summary and Conclusions: Patients with TL and DLBCL from this series management in pts was evaluated, including HBV infection and liver function had similar clinical and biological characteristics at diagnosis. GCB was more screening before R-chemo, viral replication monitoring during and after R- frequent in TL than in DLBCL. The prognosis of TL and DLBCL was similar in chemo, antiviral prophylaxis use and HBV reactivation rates. HBsAg-positive patients treated with immunochemotherapy. Supported in part by Grant RD12/0036/0029 from RTICC, Instituto de Salud (pos) pts had HBV reactivation if HBV DNA increased ≥ 1 log10 from baseline, Carlos III, Spain. if HBV DNA appeared (above the lower limit of detection) or if HBeAg appeared in HBeAg-negative (neg) pts. HBsAg-neg/HBcAb-pos pts had HBV reactivation if there was appearance of either HBsAg or HBV DNA (above the lower limit of detection). These analyses are preliminary. PB1827 TREATMENT WITH YTTRIUM-90 (90Y)-IBRITUMOMAB TIUXETAN Tablel 1. Antiviral treatment, HBV infection monitoring and HBV reactiva - (ZEVALIN®) IN DIFFUSE LARGE B-CELL LYMPHOMA: A META-ANALYSIS tion in R-chemo-treated DLBCL/FL pts. S Auger 1,* Y Duny 2, JP Daures 2, P Quittet 3 1Internal médicine and hematology, ClinicBeausoleil, 2Biostatistical and Epidemiology, INSERM Unit EA 2415, 3Hematology, University hospital, Montpellier, France

Background: Diffuse large B-cell lymphoma (DLBCL) is the most frequently diagnosed non-Hodgkin’s lymphoma (NHL). Current treatment paradigm in first line, is based on immunochemotherapy and, in case of relapse or refractory, on a salvage therapy with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). Yttrium-90 ( 90 Y)-ibritumomab tiuxetan, off label, offers a new therapeutic approach for DLBCL, both as first-line induction or consolidation and in relapsed or refractory disease. Data on this subject is increasingly being reported as well in consolidation as alone, in first line or after. Aims: To assess efficacy and find the best place of Yttrium-90 ( 90 Y)- ibritumomab tiuxetan in DCLL, we conducted a literature review and meta- analysis of randomized clinical trials and observational studies on the effect of (90 Y)-ibritumomab tiuxetan treatment in this setting, except in ASCT. Methods: The primary goal was to assess the effect of ( 90 Y)-ibritumomab tiuxetan on overall response rate (ORR) and complete response rate (CRR) then assess the 2-year overall survival (OS 2y ) and 2-year progression-free survival rates (PFS 2y ) Results: Sixteen studies were identified (399 patients) with DLBCL receiving (90 Y)-ibritumomab tiuxetan as consolidation or as treatment alone. The ORR and CRR were 74.8% (n=374) and 67.4% (n=365), respectively. Outcomes were superior when ( 90 Y)-ibritumomab tiuxetan is used in consolidation after immunochemotherapy induction at first line of treatment. OS 2y and PFS 2y were 87.5% and 82.8%, respectively. The primary toxicity was neutropenia (49.9%). Summary and Conclusions: The use of ( 90 Y)-ibritumomab tiuxetan in patients HBV screening data were available from 269/309 enrolled pts. At with DLBCL is safe and effective. Results: baseline (BL), 26 pts were HBsAg pos, 74 were HBsAg neg/HBcAb pos and 169 were double neg. HBV infection status was undefined for 40 pts. 20 HBsAg- pos, 7 HBsAg-neg/HBcAb-pos, 1 double-neg and 4 undefined pts had a history PB1828 of hepatitis. HBV DNA levels were evaluated in 18/26 HBsAg-pos, 34/74 MANAGEMENT OF HEPATITIS B VIRUS (HBV) INFECTION IN PATIENTS HBsAg-neg/HBcAb-pos, 33/169 double-neg and 7/40 undefined pts. 8/18 (PTS) RECEIVING CANCER CHEMOTHERAPY IN A REAL WORLD HBsAg-pos and 3/34 HBsAg-neg/HBcAb-pos pts were positive for HBV DNA. CLINICAL SETTING HBsAg-pos pts had a median log HBV level of 3.9 copies/mL (n=7). HBV DNA J Wu 1,* Y Song 2, L Su 3, M Zhang 4, W Li 5, Y Hu 6, X Zhang 7, Y Gao 8, Z Niu 9, levels were below the level of quantification in 1 HBsAg-pos and 3 HBsAg- R Feng 10 , W Wang 11 , J Peng 1,2 , X Ouyang 1,3 , X Li 1,4 , C Wu 1,5 , W Zhang 1,6 , neg/HBcAb-pos pts who were HBV DNA pos. Levels of ALT, AST and total

702 | haematologica | 2014; 99(s1) Milan, Italy, June 12 – 15, 2014 bilirubin were tested in 99.0%, 98.7% and 98.4% of pts, respectively. Data on and 25% respectively. After a median follow-up of 26 months, OS in the (R)- antiviral prophylaxis treatment, monitoring and HBV reactivation are in Table 1. IGEV and (R)-DHAP groups was 21 months (95% CI, 10.1-31.8 months) and Most pts who received antiviral prophylaxis were HBsAg pos-only 69% of 10 months (95% CI, 8.6-11.4 months) (p=0.179) respectively. The percentage HBsAg-pos pts were treated. By 120 d after the last R dose, some pts had of patients that proceeded to transplantation was 50% in both groups. Median already stopped prophylaxis. Not all pts were monitored for serologic markers, PFS in the (R)-IGEV and (R)-DHAP groups were 13 months (95% CI 1-24 HBV DNA and liver function during induction therapy, and monitoring declined months) and 3 months (95% CI 1.7-4.2 months) respectively (p=0.001). further after the last R-chemo dose. HBV reactivation occurred in 3 HBsAg-pos, Principal grade 3/4 toxicities in both groups were cytopenias. Overall, the toxicity 3 HBsAg-neg/HBcAb-pos and 1 double-neg pts. In contrast, investigators profile of the two regimens was comparable. Significantly, of a total 78 courses reported 1 case of HBV reactivation each in HBsAg-neg/HBcAb-pos, double- of IGEV, 53% were successfully administered in an outpatient setting. All neg and undefined pts, based on clinical experience. courses of (R)-DHAP required in-patient stay. Summary and Conclusions: This study reports HBV load in previously untreated Summary and Conclusions: In summary, (R)-IGEV represents a safe and DLBCL/FL pts receiving R-chemo as first-line therapy in China. Most Chinese effective outpatient salvage therapy for R/R lymphoma. In our cohort, patients physicians acknowledge the importance of HBV screening before initiation of R- in the (R)-IGEV group had a statistically superior PFS compared to patients in chemo. However, improvements in HBV infection monitoring and antiviral the (R)-DHAP group. Our data also suggest that subsequent transplantation treatment duration are required. Even with monitoring, HBV reactivation is not rates are comparable in both groups. In addition, (R)-IGEV lends itself to defined consistently by physicians, which may lead to underreporting of administration in an outpatient setting thus avoiding potential delays because reactivation as shown herein. By the time of analysis, some early reactivation had of inpatient bed availability, enhancing patient experience, and has health emerged, but late reactivation, especially after stopping antiviral treatment, should economic benefits. be monitored long term. Finally, standardized monitoring, follow-up strategies and education are needed for proper management of HBV infection in B-NHL pts receiving chemo. PB1830 SIGNIFICANT SURVIVAL IMPROVEMENT OF THE ELDERLY PATIENTS AND WOMEN WITH LOW/INTERMEDIATE RISK MIPI MANTLE CELL PB1829 LYMPHOMA OVER THE PERIOD OF 14 YEARS P Vockova 1,* P Klener 1, R Pytlik 1, K Benesova 1, J Stritesky 2, Z Velenska 2, COMPARISON OF VS. NON-GEMCITABINE BASED 2 3 1 1 SALVAGE CHEMOTHERAPY IN RELAPSED/REFRACTORY AGGRESSIVE R Jaksa , V Campr , M Petrova , M Trneny 1First Internal Clinic – Clinic of Hematology, 2General University Hospital in LYMPHOMA 3 D Taylor 1,* P Angelillo 1, C Ward 1, D Collins 1, R Salim 1, A Pettitt 1, A Arumainathan 1, Prague, University Hospital in Motol, Praha, Czech Republic N Kalakonda 1 1Haematology, Royal Liverpool University Hospital, Liverpool, United Kingdom Background: (MCL) is an aggressive type of B-cell non- Hodgkin lymphoma (NHL) with poor prognosis. In recent years the outcome of Background: Despite advances in immuno-chemotherapy, outcomes in patients with MCL has been improved mainly by implementation of rituximab relapsed/refractory (R/R) lymphoma remain dismal. The treatment approach, in (R), high-dose araC (HDAC) into induction regimen, consolidation with eligible patients, is intensive salvage chemotherapy followed by transplantation. autologous stem cell transplant (ASCT) and R maintenance. The optimal salvage regime remains a matter of debate with wide institutional Aims: A single center retrospective analysis of MCL patients treated since 1999 variations. (R)-DHAP (cytosine arabinoside, , dexamethasone, to 2012. ±Rituximab) remains the most commonly used regimen. Gemcitabine based Methods: We retrospectively analyzed 185 consecutive patients with confirmed regimens are, at least, non-inferior to (R)-DHAP and allow effective mobilization diagnosis of MCL treated at the Charles University General Hospital since 1999 of haematopoietic stem cells even in heavily pre-treated patients. The combination to 2012. The whole cohort comprised 71% men and 29% women with median of , gemcitabine and (IGEV) has a good profile of tolerability age of 66 years (both men and women). Most patients had advanced-stage and efficacy in R/R Hodgkin’ lymphoma (HL) and lends itself to use in an outpatient disease (stage IV= 80% patients) and adverse prognosis according to the mantle-cell lymphoma prognostic index (MIPI): MIPI high (MIPI-H)= 48.1%, setting; but data for its use in non-Hodgkin’ lymphoma (NHL) are lacking. MIPI intermediate (MIPI-I)= 23.8% and MIPI low (MIPI-L)= 24.9%. Out of all 185 Aims: To assess feasibility, safety and efficacy of (R)-IGEV for the treatment patients, 2 were not treated. Three most common types of induction therapy of patients with R/R HL and NHL. included R-CHOP (n=52), Nordic protocol (alternating 3 cycles of R-Maxi-CHOP Methods: In a retrospective cohort study, we analysed the outcome of 46 and 3 cycles of R-HDAC, n=45) and R-COP (n=26). 45 patients received ASCT. consecutive patients treated for R/R lymphoma at our institution between January Most patients (86.9%) had rituximab as part of induction. 2010 and October 2013. Patients received either IGEV or DHAP for HL and Overall response rate for all patients was 81.9% (CR/uCR= 57.9%, additional Rituximab for B-NHL. Primary outcomes were overall response rate Results: PR= 24%). Median progression-free survival (PFS) and overall survival (OS) was (ORR); PFS (from first salvage to progression, relapse, or death from any cause); 2.84 years, and 6.27 years, respectively. The median follow-up was 4.4 years. The and overall survival (OS). OS and PFS were estimated using the Kaplan-Meier analysis revealed several interesting findings. First, patients (pts) diagnosed in method and compared using the log-rank test. In addition, the likelihood of 2006-2012 (2006+) vs 1999-2005 (1999+) had significantly better PFS (median proceeding to transplantation, on an intent-to-treat basis, was assessed. 2.04 vs 3.38 years, p= 0.0222) and trend toward better OS (median 7.2 vs. 4.3 years, p= 0.11). Curiously, the age-stratified analysis revealed that only elderly patients (≥ 60 years) in 2006+ group had significantly improved PFS (median 2.74 vs. 1.63 years, p= 0.0086) and trend toward improved OS (median 4.2 vs 2.3 years, p=0.0625) compared to those in 1999+ group. The younger patients in 2006+ compared to 1999+ group had similar PFS (median 5.52 vs. 5.51 years, p= 0.884) and OS (median undefined in both subgroups, p= 0.784). The reason for the improved outcome of the elderly patients in recent years is probably a consequence of introduction of rituximab maintenance. In the elderly groups 1999+ and 2006+ two of 44 and 32 of 66 pts received rituximab maintenance, respectively. The elderly pts 2006+, who received rituximab maintenance (compared to those, who did not) had higher PFS (median 4.5 vs 2.23 years, p= 0.0055) and OS (median undefined vs 3.41 years, p= 0.0018). Second, MIPI discriminated well into 3 subgroups of patients only in the whole cohort. However, in the age-stratified analysis there remained only two relevant MIPI subgroups: MIPI-I merged with MIPI-H (in younger pts) or with MIPI-L (in elderly pts). Finally we observed trend toward better OS in the subcohorts of women with MIPI-L and MIPI-I compared to men (MIPI-L median undefined vs 8.48 years, p= 0.0692; MIPI-I median 10.51 vs 4.56 years, p= 0.0657). PFS was significantly prolonged Figure 1. in women with MIPI-I compared to men (median 8.31 vs 5.59 years, p= 0.539), but did not differ in women with MIPI-L (median 8.04 vs. 2.44 years, p= 0.0237). Summary and Conclusions: On the large single center cohort of unselected Results: We analysed 46 consecutive patients treated at our institution for R/R MCL patients we demonstrated significant outcome improvement of elderly HL and NHL between January 2011 and October 2013. Median age at salvage patients but not younger patients during the last 7 years. We found that MIPI was 57 (19-78) yrs, 67% of the patients were male. At diagnosis, 86% of patients discriminated only two prognostic subgroups when used in age-defined cohorts had stage III/IV disease, and 15 patients had a diagnosis of HL. In the (R)-IGEV of patients. Finally, women with low and intermediate risk MIPI appeared to have group the ORR rate, after 2 courses, was 44% with a CR rate of 36% (as better outcome compared to man. assessed by PET-CT). ORR and CR rates in the (R)-DHAP group were 27% Financial support: PRVOUK-27/LF1/1, IGA-MZ NT/13072-4.

haematologica | 2014; 99(s1) | 703 19 th Congress of the European Hematology Association

PB1831 incidence and predictors of delayed MTX clearance, hepatic and nephrotoxicity. Methods: We conducted a retrospective analysis of pts receiving ≥1 cycle of HD- CLINICAL IMPLICATIONS AND PROGNOSTIC SIGNIFICANCE OF MTX for histologically aggressive NHL. Clinical and pharmacy databases were POSITRON EMISSION TOMOGRAPHY (PET/CT) IN PATIENTS WITH reviewed from 2004-2013 inclusive. Data collected included patient sex, age, DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) AFTER R-CHOP diagnosis, MTX dose and number of cycles, rate of MTX infusion, peri-treatment CHEMOIMMUNOTHERAPY radiological contrast exposure, baseline bicarbonate level as a measure of urine T P Vassilakopoulos 1,* A Kanellopoulos 1, S Papageorgiou 2, G A Pangalis 3, alkalinisation (mmol/L), nadir bicarbonate level during MTX exposure, peak serum A Anastasopoulou 4, M Moschogianni 5, Z Galani 1, K Petevi 1, G Boutsikas 1, and 24hr post-infusional MTX levels ( μmol/L), time to clear MTX defined as level SI Kokkoris 6, M Dimou 7, L Papageorgiou 1, T Tzenou 7, G Gainaru 1, A Koutsi 1, ≤0.05 ( μmol/L) and hepatic and renal toxicity as defined by CTCAE v4.0. E Pessach 7, V Telonis 1, S Sachanas 3, N Viniou 4, E Variami 4, MC Kyrtsonis 7, Results: A total of 90 pts (54M, 36F) met the inclusion criteria with median age M N Dimopoulou 1, P Tsirigotis 2, E Plata 1, P Tsaftaridis 1, M Siakantaris 4, of 61.7yrs (19.8-82.6); 36 (40%) were >65yo (cut-off age for receiving MTX > P Panayiotidis 7, J Meletis 1, H Ioannidou 2, V Pappa 2, M K Angelopoulou 1, 1g/m 2). A total of 161 cycles were delivered; 72 at 3g/m 2, 65 at 1g/m 2 and 24 at K Konstantopoulos 1 other doses (0.5, 1.5 or 2g/m 2). 71/90 (79%) pts received both planned cycles. 1Department of Haematology, Laikon General Hospital, 2Second Propedeutic 88% of 32 pts having 1g/m 2 in cycle 1 had 1g/m 2 in cycle 2, only 61% of 44 pts 2 2 Departmant of Internal Medicine, Attikon Hospital, 3Department of having 3g/m had 3g/m in cycle 2; 9% had a dose reduction, 30% did not have Haematology, Athens Medical Center, 4First Department of Internal Medicine, a second cycle. Most HD-MTX was given as a 24-hr infusion, only 4 pts had a Laikon General Hospital, 5Athens Medical Center, 6Transfusion Department, 3hr infusion with 75% having significant toxicity or delayed clearance prohibiting 7 cycle 2. The median peak MTX level ( μmol/L) was 34.95 (5.18-125.95) in pts Attikon Hospital, First Propedeutic Department of Internal Medicine, Laikon 2 General Hospital, Athens, Greece having 3g/m (29/72 courses recorded) and 15.38 (1.21-22.19) in pts having 1g/m 2 (33/65 courses recorded), with median 24h post-infusion level of 0.37 (0.10-12.66) and 0.28 (0.03-3.51) respectively. The 24h MTX level correlates Background: Αbout 30-40% of patients with DLBCL are primary refractory or better with delayed clearance then end of infusion level does (R 0.77 vs. R 0.17). relapse after first line treatment with the R-CHOP regimen. Among responders If 24h level >2.0, then 5/6 (83%) had delayed clearance; <2.0 then only 21/80 had according to the IWC criteria, many patients still have post-treatment residual delayed clearance, P=0.009. Median time to clear MTX was 57h (25h-137h) with masses. Therefore, PET/CT is increasingly used for the identification of patients median length of hospital stay of 98h (64h-385h). Delayed clearance, defined as with active disease at the end of treatment, although relevant data are scarce MTX level >0.05 μmol/L at 72h, was observed in total of 39 cycles (24%). Grades in the literature. 1-3 hepatotoxicity was observed in 26.7%, 10.6% and 6.8% of cycles respectively. Aims: The retrospective analysis of PET/CT findings in patients with DLBCL Grades 1-4 nephrotoxicity was observed in 53.4%, 8.7%, 2.5% and 0.6% of after conventional response to R-CHOP and the assessment of their impact on cycles respectively. We analysed our postulated risk factors as predictors of outcome in comparison to established prognostic factors. delayed clearance or nephrotoxicity ≥G2 independently for cycles 1 and 2 Methods: From 2004 to 2013, 151 patients with DLBCL who achieved CR, CRu, because these are likely to represent different populations given most pts who or PR by conventional radiographic imaging (according to IWC) underwent have toxicity in cycle 1 usually don’t have a second cycle. The only significant posttreatment PET/CT. All patients had been treated with 4-8 cycles of R-CHOP finding was an association between MTX 1g/m 2 in cycle 1 and delayed clearance or similar anthracycline-containing immunochemotherapy regimens. PET/CT but not nephrotoxicity. Overall, 74% (14/19) pts with nephrotoxicity ≥G2 had was performed at the treating haematologist’s discretion, but availability was also delayed clearance, but only 49% (14/39) pts with delayed clearance had an issue, particularly during the earlier years of the study. The primary end-point nephrotoxicity ≥G2. of the analysis was progression free survival (PFS). PET/CT scans were Summary and Conclusions: HD-MTX associated toxicity resulted in interpreted according to the International Harmonization Project criteria. suboptimal delivery of CNS prophylaxis in 21% of our patients. A 24h level of Results: The main baseline patients’ characteristics were: median age 61 (18-89), >2.0 predicts for much greater risk of delayed clearance and could be a red flag 65% male, 55% stage II Ι/Ι V, 17% ECOG PS ≥2, 23% ≥2 E-sites, 53% abnormal for more aggressive intervention. Unlike previous reports of age as a predictor LDH, IPI-L 42%,IPI-LI 21%,IPI-HI 24%, IPI-H 14%. Among the 151 patients, 117 of toxicity, age-based dose adjustment diminishes this risk association. (77%) became PET(-) (including 11 patients with indeterminate findings) and Patients having dose-adjusted MTX at 1g/m2 were more likely to have delayed 34/151 (23%) remained PET(+). The 4-year PFS was 86% vs 40% for PET(-) and MTX clearance but not nephrotoxicity. Other MTX doses, low serum PET(+) patients respectively (p<0.0001). Αmong PET(-) patients, 107/117 bicarbonate as an indirect assessment of poor urine alkalinisation and rate of remained in complete remission for a median follow-up of 25 months from the date infusion were not associated with toxicity. of PET/CT. Among PET(-) patients, 10/117 relapsed. PS ≥2 was associated with inferior PFS in PET(-) patients (4-year PFS 89% vs. 69% for patients with PS 0- 1 vs. 2-4; p=0.02). Marginally significant trends towards inferior PFS among PET(- PB1833 ) patients were also observed for males, multiple extranodal involvement and bone marrow involvement (0.102 or 24% (7/29) of cases PET showed a lower number of disease sites than CECT. multiple/specific extranodal sites of involvement (testis, breast, kidney, adrenal, In 1 pt (1/29, 3%) we observed a PET positivity, with CECT negativity after BM, or epidural)] at our centres receive 2 courses of intravenous high-dose diagnostic lymphnode biopsy. Additional sites identified by PET were both methotrexate (HD-MTX) as CNS parenchymal prophylaxis. HD-MTX can nodal and extra-nodal: new nodal sites in 19 pts, spleen in 2 pts, bone in 3 pts, however result in significant toxicity leading to treatment delay so identification nasopharinynx, pancreas, muscle, bowel and testicle in 1 pt each. FDG-PET of predictors of toxicity is crucial. results led to change the an Ann Arbor stage in 44.8% (13/29) of cases, with Aims: The aim of this study was to examine HD-MTX pharmacokinetics, the an up-staging in 37.9% (11/29) of pts. At end-of-therapy restaging, 62% (18/29)

704 | haematologica | 2014; 99(s1) Milan, Italy, June 12 – 15, 2014 pts had a negative FDG-PET scan; CECT was concordant and consisting with Hematology, Hospital del Mar, Barcelona, 3Department of Hematology, Institut complete response in 78% (14/18) of cases, while in the remaining 22% (4/18) Catalá d´Oncologia, L´Hospitalet de Llobregat, 4Department of Hematology, of cases CECT showed a partial response with residual lesions. In the 11/29 Hospital Germans Trias y Pujol, Badalona, 5Department of Pathology , Hospital (38%) final PET positive pts, CECT was concordant and pointed out a partial Vall d´Hebron, Barcelona, Spain response in 7/11(64%) pts, while was negative in 4/11 (36%) cases. A survival analysis according to final PET result was not performed due to the low number Background: Post-transplant lymphoproliferative disorders (PTLD) are of final PET positive pts. No statistically significant difference was found in PET lymphoid neoplasms that develop after stem-cell or solid behaviour between different histological subtypes. (SOT) associated with immunosuppressive therapy (IS) and Epstein-Barr virus Summary and Conclusions: In conclusion, in our hands FDG-PET allowed a (EBV) infection. Burkitt’s monomorphic PTLD (BM-PTLD) is an uncommon and more accurate baseline disease extension evaluation: it could identify additional not properly described subtype of PTLD. sites, both nodal and extra-nodal, in two-thirds of pts. A change in clinical stage Aims: To gain insight into this rare lymphoma, the histological and clinical according to FDG-PET was observed in 44.8% of cases, with an upstaging in features of a series of adult diagnosed with BM-PTLD in four transplant centers the majority of pts. A high level of concordance was observed between PET and were retrospectively reviewed. CECT at restaging. Nevertheless, PET pointed out minimal residual disease in Methods: All patients diagnosed with BM-PTLD between February 1996 and 22% of final CECT negative pts and complete remission in 36% of final CECT November 2013 were recorded and analyzed. Patients with PTLD negative for positive pts, allowing to optimize response evaluation in small but critical C-MYC breaks and/or diagnosed with unclassifiable lymphoma with subgroups of pts. intermediate features between DLBCL and BL were excluded. Results: Ten patients with the diagnosis of BM-PTLD were included. Seven patients were female and the median age at diagnosis was 41 years (range, 25- PB1834 52 yrs). All patients underwent SOT (7 kidney, 2 liver, and 1 lung). Median time of the diagnosis of PTLD from transplant was 94 months (range, 27-197 mos), HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL and all patients were receiving IS, 7 with tacrolimus and three with cyclosporine. TRANSPLANTATION IN FIRST LINE TREATMENT FOR HIGH-RISK The PTLD was diagnosed in stage I-III in 4 patients and in stage IV in 6. Serum DIFFUSE LARGE B CELL LYMPHOMA (DLBCL) IN THE RITUXIMAB ERA: LDH was increased in 6/8 patients, and β microglobulin in 5/8. AN INTENTION TO TREAT-ANALYSIS 2 MC Tisi 1,* E Maiolo 1, F D’Alò 1, S Bellesi 1, F Sorà 1, P Chiusolo 1, L Laurenti 1, analyses (n=8) revealed that all cases were CD20, CD10, M Picardi 1, E Alma 1, LM Larocca 2, S Sica 1, S Hohaus 1 and BCL-6 positive and negative for BCL-2. Ki67 expression was >95% in all 1Institute of Hematology, 2Institute of Pathological Anathomy, Catholic cases. FISH showed the presence of the MYC translocation in all cases analyzed, University, Rome, Italy while BCL2 and BCL6 translocations were excluded in all cases examined (5/5). In situ hybridation for EBV was positive in 3 of 5 cases. Six patients were treated Background: The combination of Rituximab and CHOP (R-CHOP) is considered to be the standard treatment for patients (pts) with newly diagnosed with immunochemotherapy, 4 with R-CHOP along with CNS intrathecal diffuse large B-cell lymphoma (DLBCL). Treatment results are still unsatisfactory prophylaxis and 2 with the Burkimab regimen (Ribera et al. , Cancer 2013;119 in a significant proportion of patients, particularly in those with a high-risk 1660) that contains high-dose chemotherapy along with rituximab. One additional disease defined by the IPI score. The use of high-dose chemotherapy with patient received 4 courses of rituximab with the withdrawal of IS. Finally, 3 patients autologous stem-cell transplantation (ASCT) is standard clinical practice for diagnosed in the pre-rituximab era were treated with CHOP (n=2) and one with patients with relapsed/refractory DLBCL, while its significance as consolidation a combined regime (etoposide, cyclophosphamide, methotrexate, , in first-line treatment remains unclear. and vincristine). All patients that finished the initial treatment (n=8) obtained a Aims: We analyzed safety and effectiveness of R-CHOP followed by salvage complete remission (CR). Three patients died, two during the first course of chemotherapy and ASCT for patients with young (<65 years) high-risk DLBCL, treatment due to PTLD progression and a sepsis, and another one due to defined by an age-adjusted IPI score of 2/3, for whom from 2004 on our unrelated causes. Two patients that relapsed 12 and 9 months after R-CHOP and institutional guidelines recommended ASCT as consolidation. We analyzed rituximab monotherapy, respectively, were salvaged with the Burkimab regimen prognostic factors in this group. achieving a second CR. After a median follow-up of 35 months (range 1 to 120), Methods: The treatment program consisted of 4 cycles R-CHOP-14 followed 7 patients remain in CR. The 3-year progression-free survival and overall survival by 3 cycles of a DHAP-like salvage regimen, R-MICMA (Sorà et al, Cancer was 55% and 80%, respectively, for the whole series, and of 63% and 100% for 2006; 106: 859), and consolidation with -Melphalan supported with the 7 patients receiving rituximab-containing therapies. ASCT. We observed 76 consecutive patients (median age 50 years, range 15- Summary and Conclusions: In this retrospective series BM-PTLD appears as 64 years; 32 females and 44 males) diagnosed between May 2004 and January an infrequent and aggressive variety of PTLD usually diagnosed late in the 2013 with DLBCL who had an age-adjusted IPI score of 2 or 3. Response was evolution after transplant and in advanced stage of the disease. This lymphoid assessed according to Cheson criteria (Cheson et al, JCO 1999; 17:1244). proliferation seems to have an excellent response to the immunochemotherapy Results: Nine of 76 patients (12%) were not eligible for the treatment program combinations, including R-CHOP or to more intensive regimens like Burkimab. that included ASCT. Reasons were important comorbidities in 6 pts (1 cardiac, 2 For those patients not candidate to intensive regimens, R-CHOP could be an neurologic, 1 hepatic, 1 hematologic, 1 renal) and start of another treatment excellent therapeutic alternative. A nation-wide collection of cases of BM-PTLD regimen (CODOX-M/IVAC in the suspicion of a ) in 3 is now ongoing. pts. Response after 4 cycles R-CHOP was CR/CRu in 40/67 pts (60%), PR in 21/67 pts (31%) and NR in 6/67 (9%). Sixty-one patients went on to salvage chemotherapy with R-MICMA, while 6 pts in CR/CRu continued R-CHOP, and 53 PB1836 pts were transplanted. Reasons not to proceed to transplant were progressive disease (3 pts), infections (3 pts), mobilization failure (1 pt) and patient’s decision CLINICAL RELEVANCE OF SOME LYMPHANGIOGENIC AND INFLAMMATORY CYTOKINS IN DIFFUSE LARGE B-CELL LYMPHOMA (1 pt). The 3-year EFS and OS of the entire group of 76 patients were 67% (95% 1 * 2 3 4 3 CI, 55-76) and 71% (95% CI, 59-80%), respectively. The 3-year EFS and OS of D Wolowiec , A Wosztyl , E Ziolkowska , E Robak , T Robak , A Korycka- 3 transplanted patients were 70% (95% CI, 55-80) and 76% (95% CI, 62-85). Wolowiec 1 Factors associated with inferior EFS were age-adjusted IPI score (2 vs. 3, Department of Hematology, Wroclaw Medical University, Wroclaw, 2 3 p=0.004) and disease status after 4 cycles R-CHOP (p=0.01) in univariate and Department of Hematology, Holycross Cancer Center, Kielce, Department of multivariate analysis. These differences were also retained in the group of patients Hematology, 4Department of Dermatology, Medical University of Lodz, Lodz, who received ASCT, with a three-years EFS of 78% in pts with an age-adjusted Poland IPI score 2 vs 46% in pts with an age-adjusted IPI score 3 (p=0.003), suggesting that ASCT is insufficient for highest risk patients. Background: Pathological angio- and lymphangiogenesis, consisting in the Summary and Conclusions: Our findings of an intention-to-treat, single centre new blood and lymphatic vessels development, within and around a malignant experience indicate that 88% of patients with high-risk DLBCL and age <65 tumour, are differently regulated and bear different significance for neoplastic years are eligible for a treatment strategy that includes ASCT, and 70% will development, including DLBCL. VEGF-C,VEGF-D and VEGFR-3 are crucial for eventually receive ASCT as part of their first-line treatment. Consolidation with lymphangiogenesis, but the relationship between their plasma levels and clinical upfront ASCT for high-risk DLBCL is a feasible and promising therapy also in course of DLBCL is unknown. Similarly, there are no reports on the role of the Rituximab era, but there are still subsets of patients that continue to have inflammatory cytokine IL-17B and its receptor IL-17BR in DLBCL. a poor prognosis despite ASCT, and addition of new biologic drugs, as tyrosine Aims: The aim of our study was to assess the plasma levels of VEGF-C, VEGF- kinase inhibitors, have to be tested to improve outcome in these patients. D, VEGFR-3, IL-17B and IL-17BR in DLBCL patients upon diagnosis in order to evaluate the predictive value of those cytokines as to the achievement of complete remission (CR) after standard R-CHOP treatment, and their PB1835 prognostic value regarding the overall survival (OS). POST-TRANSPLANT MONOMORPHIC BURKITT’S LYMPHOMA: CLINICAL Methods: The study was performed in 55 untreated DLBCL NOS type patients CHARACTERISTICS AND OUTCOME OF A MULTICENTER SERIES after their written consent (38 M, 17 F), aged 23-88 yrs (mean 65.4), and 30 S Bobillo Varela 1,* P Abrisqueta 1, P Olivera 1, P Barba 1, A Salar 2, E Gonzalez healthy control individuals (9 M, 21 F), aged 39-88 yrs (mean 61.1). For each Barca 3, JM Sancho 4, J Montoro 1, C Carpio 1, J Castellví 5, A López 1, F Bosch 1 patient blood count, serum LDH activity, b-2microglobulin, albumin and CRP 1Department of Hematology, Hospital Vall d´Hebron , 2Department of concentrations were determined. The clinical stage of the disease and the general

haematologica | 2014; 99(s1) | 705 19 th Congress of the European Hematology Association condition were determined according to the Ann Arbor classification, ECOG and PB1838 the IPI system. The patients received 6-8 courses of the standard 21-R-CHOP regimen, and 24 of them (43,6%) achieved CR. The cytokines plasma 90Y-IBRITUMOMAB TIUXETAN CONSOLIDATION AFTER AUTOLOGOUS concentrations were established by ELISA method. Results were processed STEM CELL TRANSPLANTATION IMPROVES SURVIVAL OF statistically with the Mann-Whitney and the Wilcoxon tests, the Spearman rank INTERMEDIATE/HIGH-RISK DIFFUSE LARGE B-CELL LYMPHOMA 2 PATIENTS NOT RESPONDING ADEQUATELY TO FIRST correlation coefficient and the chi test. The Kaplan-Meier survival curves were 1 * 1 2 1 3 used for estimation of OS probability and compared with the log-rank test. P Mondello , G Altavilla , E Derenzini , V Pitini , M Mian 1Medical Oncology, Universitary Hospital “G. Martino”, Messina, 2Hematology, Results: Lymphangiogenic cytokines plasma levels did not significantly differ 3 between patients and controls, except VEGFR-3 which was higher in patients “L. and A. Seràgnoli”, S. Orsola-Malpighi Hospital, Bologna, Hematology, than in controls (75.8±42.1 and 45.7±16.7ng/ml; respectively; p=0.0007). Hospital “S. Maurizio”, Bolzano, Italy VEGFR-3 and VEGF-C values were significantly higher in patients with IPI (3- 5) than with IPI<3 (63.5±40.6 and 83.5±41.8ng/ml for VEGFR-3; p=0.048, and Background: Diffuse large B-cell lymphoma (DLBCL) is the most common 2309.0±1729.5 and 2895.6±1140.5pg/ml; p=0,02 for VEGF-C). VEGFR-3 was lymphoma entity, accounting for approximately 25-30% of new cases of non- positively correlated with β-2 microglobulin (R=0.37; p=0.01). VEGF-D was Hodgkin’s lymphoma. Up to now the prognosis of high-risk patients, namely correlated positively with β-2 microglobulin (R=0.35; p=0.02) and LDH (0.35; those with an elevated IPI, bulky disease, involvement of central nervous p=0.01) and negatively with serum albumin concentration (R=-0.44;p=0.001). system or testes, is poor due to early relapses. Aggressive salvage treatments The concentration of IL-17BR was significantly higher in patients than in to improve their outcomes were unsatisfactory. Therefore a consolidation controls (2,7±3,3 and 1,4±1,1pg/ml; respectively; p=0.03). There was a therapy after early salvage regimen with autologous stem cell trasplant (ASCT) significant relationship between the concentrations of IL-17B and IL-17BR, and could reduce the relapse rate and prolong survival. this relationship was stronger in the control group (R=0.89; p<0.0001) than in Aims: This analysis was performed to evaluated whether the additional yttrium- DLBCL patients (R=0.50; p=0.0001). We did not find a relationship between the 90-ibritumumab tiuxetan (90Y-IT) after early salvage treatment is able to plasma concentration of any cytokine and the achievement of CR. The OS improve the outcome of high-risk DLBCL. probability curves did not significantly differ between the patients with Methods: We retrospectively assessed 37 patients affected by intermediate- concentrations of any evaluated cytokine above versus below the median value, high risk DLBCL not in complete remission after 3 cycles od R-CHOP but the Cox regression model showed negative prognostic impact of high chemotherapy. All were addressed to early salvage treatment with ASCT and VEGF-D concentration on OS (HR=1.005, 95% CI, p=0.008). 20 eligible patients underwent additional 90Y-IT consolidation. Salvage treatment consisted of 3-4 courses of R-DHAP followed by stem cell Summary and Conclusions: Relationship between plasma levels of lymphangiogenic cytokines and some markers of disease activity may reflect mobilization with cyclophosphamide (3 g/m2) and triple ASCT with a high-dose an influence of lymphangiogenesis on DLBCL progression. The negative impact of cytarabine conditioning regimen (3-4 g/m2 days 1-4). of VEGF-D value on OS warrants further studies. Higher IL-17BR plasma Results: After completion of the salvage treatment, in the 90Y-IT group 45% concentration and its weaker correlation with IL-17B in patients than in healthy achieved a complete remission (CR) and 55% a partial remission (PR) compared controls might indicate a deregulation of the IL-17BR expression in DLBCL to 94% and 6% in the other group. After 90Y-IT consolidation all achieved a CR. Adverse events after 90Y-IT treatment consisted of moderate transient hematologic toxicity. During the 3-year median follow-up period, 50% in the 90Y- IT group relapsed, compared to 82.3% in the other cohort (p=0.002). Progression PB1837 and disease free survival (Figure 1) were significantly longer in the 90Y-IT group. COMPARISON OF PROGNOSTIC IMPACT OF ABSOLUTE LYMPHOCYTE However, probably due to the relatively short follow-up period, no difference in COUNT (ALC), ABSOLUTE MONOCYTE COUNT (AMC), ALC/AMC overall survival (OS) was observed. PROGNOSTIC SCORE AND ALC/AMC RATIO IN PATIENTS WITH DIFFUSE LARGE B CELL LYMPHOMA O Markovic 1,2, * L Popovic 3,4, D Stanisavljevic 5,6, D Marisavljevic 1,2, M Toodorovic 2,7 1Hematology, Clinical Hospital Center “Bezanijska kosa” , 2Mecial Faculty, University of Belgrade, Beograd, 3Medical faculty, Novi Sad, Novi Sad, 4Hematology, Institute of Oncology, Sremska Kamenica, 5Mecial Faculty, University ofBelgrade, 6Institute of statistics, 7Hematology, Institute of Hematology, Beograd, Serbia

Background: The combination of absolute lymphocyte count (ALC) and absolute monocyte count (AMC) at diagnosis have prognostic relevance in patients with diffuse large B cell lymphoma (DLBCL). Aims: Aims: The present study was designed to investigate prognostic significance of ALC and AMC and to determine whether ALC/AMC ratio or ALC/AMC prognostic score is better predictor of outcome in DLBCL. Figure 1. Methods: We retrospectively analysed prognostic significance of ALC and AMC, ALC/AMC ratio and ALC/AMC prognostic score at diagnosis in 222 Summary and Conclusions: 90Y-IT consolidation after early salvage DLBCL patients treated with R-CHOP. ALC/AMC score was determined chemotherapy improves treatment responses and reduces the percentage of according to Wilcox’s model. Namely, the patients were stratified into three risk relapses without significant additional toxicities. However, the follow-up time groups: low risk (normal AMC and ALC), intermediate (high AMC or low ALC), was not long enough to observe a difference in OS. Prospective confirmatory and high risk (high AMC and low ALC). data is needed. Results: ROC analysis showed that optimal cut-off values of AMC and ALC/AMC ratio with the best sensitivity and specificity were 0.59x109/L and 2.8, respectively. Cut-off of ALC was determined according to the literature data (1x109/L). Median PB1839 lymphocyte count was 1.4x109/L and the range was 0.2-13x109/L. Median of monocyte count was 0.5x109/L and the range was from 0.1 to 3.9x109/L. Median MYC PROTEIN EXPRESSION IS THE POOR FACTOR IN DIFFUSE LARGE of ALC/AMC ratio was 2.8, and range was from 0.33 to 57. Distribution of patients B CELL LYMPHOMA TREATED WITH RCHOP J Ouyang 1,* M Zhou 1, J Wang 1, J Xu 1, B Chen 1, XS Fan 2, HY Wu 2 according to ALC/AMC prognostic score was as follows: low risk 91(41.0%), 1Hematology, 2pathology, the DrumTower Hospital of Nanjing University intermediate risk 99(44.6%) and high risk 32(14.4%) patients.Low ALC, high Medical School Nanjing China, Nanjing, China AMC, low ALC/AMC ratio and high ALC/AMC prognostic score were in significant association with lower rate of therapy response and survival. In contrast, these Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous parameters were not in significant correlation with relapse rate. The patients with group of neoplasma. It is increasing important to search the predictive low ALC, “high” AMC, low ALC/AMC ratio and high ALC/AMC prognostic score biomarkers which could identify cases who will fail to RCHOP. at diagnosis had significantly shorter EFS and OS. In multivariate analysis all Aims: This study aims to investigate the prognostic significance of the MYC tested parameters (ALC, AMC, ALC/AMC prognostic score and ratio) are protein expression in DLBCL patients treated with RCHOP. independent risk factors along with “bulky” disease and IPI. Methods: A total of sixty patients with DLBCL from 2008 to 2013 were included. Summary and Conclusions: All tested parameters (ALC, AMC, ALC/AMC Formalin-fixed paraffin-embedded(FFPE) tumor samples were analyzed for score and ratio) may be useful prognostic factors in DLBCL patients. ALC/AMC MYC protein expression and divided into high or low MYC group. The MYC score has a slight advantage as it allows the classification of patients into three protein expression and the international prognostic variables were evaluated. prognostic groups. Further studies are needed to determine which of these Results: The high MYC protein expression predicted a shorter 3-year parameters has the highest predictive value. estimated overall survival (OS) and progression-free survival (PFS) versus the

706 | haematologica | 2014; 99(s1) Milan, Italy, June 12 – 15, 2014 low MYC protein expression (57% vs. 96%, P<0.001 and 50% vs. 96%, P= Summary and Conclusions: Recent results have clearly shown that via CCL5, 0.001, respectively). Multivariate analysis confirmed the prognostic significance lymphoma B cells can recruit monocytes which in turn support the survival and of the MYC protein expression for both OS (HR, 11.862; 95% CI, 1.462-96.218; proliferation of neoplastic B cells and suppress the proliferation of normal T cells. P= 0.021) and PFS(HR, 6.233; 95% CI, 1.292-30.071;P=0.023). MYC protein Our results confirm the hypotesis that the evaluation of LMR at diagnosis is a expression with IPI score distinguished patients into three risk groups with simple and robust tool to better define clinical response and long-term outcome different 3-year OS rates (X 223.079; P<0.001) and distinct 3-year PFS rates of DLBCL patients receiving immunochemotherapy. Further study are needed 2 (X 15.862; P<0.001). to assess the role of LMR in DLBCL at diagnosis, supporting the idea that it Summary and Conclusions: the MYC protein expression is an important could be incorporated into the IPI stratification. independent inferior prognostic factor for survival in patients with DLBCL treated with RCHOP. The combinative model with IPI score and MYC protein expression could stratify DLBCL patients into prognostically relevant subgroups PB1841 more effectively than either the IPI or the MYC alone. HIGH-DOSE METHOTREXATE CONSOLIDATION IN POOR-RISK DIFFUSE LARGE B-CELL LYMPHOMA IS ASSOCIATED WITH IMPROVED PB1840 PROGRESSION FREE SURVIVAL M Gilbertson 1, J Shortt 1,2, G Grigoriadis 1,2, S Patil 1,3, G Gregory 1, Z Wang 1, PROGNOSTIC SIGNIFICANCE OF LYMPHOCYTE/MONOCYTE RATIO B Kumar 4, SS Opat 1,2, * (LMR) AT DIAGNOSIS IN A COHORT OF PATIENTS WITH DIFFUSE LARGE 1Haematology, Monash Health, 2Faculty of Medicine, Nursing and Health B CELL LYMPHOMA (DLBCL) TREATED WITH IMMUNOCHEMOTHERAPY: Sciences, Monash University, Clayton, 3Haematology, Alfred Health, A SINGLE CENTRE EXPERIENCE. Melbourne, 4Anatomical Pathology, Monash Health, Clayton, Australia E Doni 1,* A Belotti 1, F Rossini 1, I Casaroli 1, S Bolis 1, S Pezzatti 1, S Bozzani 1, L Verga 1, P Perfetti 1, P Pioltelli 1, EM Pogliani 1 Background: While the majority of patients with Diffuse large B-cell lymphoma 1Hematology Unit, S. Gerardo Hospital, Monza, Italy (DLBCL) can expect to be cured with R-CHOP chemotherapy, the outcome for Background: Diffuse large B-cell lymphoma (DLBCL), the most common patients with poor risk disease is less certain with approximately 50% of patients subtype of lymphoid neoplasm, is characterized as an aggressive lymphoma eventually succumbing to their disease. Dose intense regimens have largely with heterogeneous clinical behaviors. A large number of studies have therefore failed to improve outcomes, and are associated with increased toxicity. However focused on the search for surrogate biomarkers which are immunologically certain regimens may have a role in younger poor risk patients. relevant and can serve as prognostic factors. Lymphopenia, a surrogate marker The association of poor-risk disease with central nervous system (CNS) of immune suppression, was found to predict survival in DLBCL. Monocytes, recurrence has led many centres to advocate the use of systemic high-dose which are considered immunologically relevant and are regarded as a surrogate methotrexate (HD-MTX) consolidation in poor-risk patients. Since 2007 our marker of the , were also recently reported to be a centre has been consolidating patients deemed to be at high-risk of CNS prognostic factor in DLBCL. Although the introduction of rituximab combined recurrence including those with IPI≥3, involvement of a high-risk site (testis, with chemotherapy has greatly improved survival outcomes in DLBCL patients, ovary, breast, kidney, extradural or skin) or those with two involved extra nodal there is limited available data about prognostic value of lymphocyte/monocyte sites and a raised lactate dehydrogenase with two cycles of intravenous ratio (LMR) in DLBCL patients (pts) in the rituximab era. methotrexate 3g/m 2 and rituximab 375mg/m 2 following the completion of R- Aims: We investigated the prognostic role of LMR in terms of complete CHOP. HD-MTX is only administered to patients in CR after completion of R- remission (CR) after first line treatment, overall survival (OS) and progression CHOP with adequate performance status. free survival (PFS) in a cohort of pts with DLBCL and treated with Aims: In this study we examine the effect of HD-MTX on overall survival (OS) immunochemotherapy at our istitution. and Progression Free Survival (PFS) in patients with poor-risk DLBCL. Methods: We retrospectively analyzed data from a total of 133 DLBCL pts Methods: Patients were included in the study if they had DLBCL diagnosed treated at our institution from January 2007 to July 2013. The median age of according to WHO 2008 criteria, an R-IPI ≥ 3, received two or more cycles of all pts at diagnosis was 64 years (range of 18–92 years). Pts were treated with R-CHOP-like chemotherapy, and had adequate clinical information that included immunochemotherapy with or without anthracycline (RCHOP or RCVP). We baseline clinical characteristics, treatment regimens and clinical outcome. analyzed different LMR cut-off values and we found that the most discriminative Patients were excluded if they were too frail to receive chemotherapy or failed LMR was 2.4; the absolute monocyte count (AMC) and absolute lymphocyte to achieve a CR following R-CHOP therapy. A total of 92 patients met the entry count (ALC) were derived from pre-treatment CBC counts. Survival curves criteria of which 17 received HD-MTX. Survival correlates were analysed by Cox according to Kaplan-Meyer method were employed to estimate PFS and OS. regression using SPSS. Log rank test was used to analyze differences. OS, PFS and relapse rate were While patients receiving HD-MTX were younger (median age 69 v. 74), defined by the standard criteria. Results: the proportion over 60 years was similar in both groups; (HD-MTX 83% v. Results: The median follow-up time of the surviving pts was 24 months. 72 pts (54.1%) had localized disease (Ann Arbor stage I–II) and 61 extended disease standard 85%). The proportions with advanced stage (100% v 85%) raised (Ann Arbor stage III–IV); among them, 16 pts and 8 pts had extranodal LDH (82% vs. 80%) and ECOG>2 (17% vs. 11%) were also similar, however localization, respectively. Based on the aaIPI score, 13 patients were in the the HD-MTX group had fewer patients with ECOG >1 (41% v. 60%). All patients aaIPI 0 group (9.7%), 50 pts in the aaIPI 1 group (37.6%), 48 pts in the aaIPI received Rituximab containing chemotherapy regimens, with both groups 2 group (36%) and 22 pts in the aaIPI 3 group (16.5%). An LMR value<2.4 was receiving a median of six cycles (range 3-6). associated significantly with an advanced clinical stage (p=0.007), and a higher The median follow up of surviving patients was 2.5 years. Patients who received IPI score (p=0.004) and higher aaIPI (p=0.002). In the entire cohort, 90 pts HD-MTX had improved 5 year PFS: 65% vs. 34% (HR 0.50, p=0.048) and a obtained CR after first line treatment, while 43 pts did not obtain CR. CR rate trend to improved OS 73% v. 44% (HR 0.50, P =0.082) This was mainly (55% vs 61%) and 2 year-OS (85% vs 87%) were similar for pts with LMR<2.4 attributable to a reduction in the five year systemic rela:pse rate: 17.6% vs. and for pts with LMR>2.4. Among 40 pts with an LMR>2.4 only one relapsed 38.7% (HR 0.46, P=0.063). No difference in the rate of CNS recurrence was (6 months after CR), while 7/50 pts with LMR<2.4 relapsed after 4-22 months, evident however events in both groups were uncommon. The regimen was well with 2 year-PFS of 86% vs 96%, as shown in Figure 1 (p=0.07). tolerated with no severe toxicity (Figure 1).

Figure 1. Figure 1. Progression free survival, IPI 3, 4, 5.

haematologica | 2014; 99(s1) | 707 19 th Congress of the European Hematology Association

Summary and Conclusions: The use of HD-MTX is associated with Results: Over this period, 29 (7.25%) patients with biopsy proven tFL were improved PFS and a trend to improved OS when used as consolidation identified from a total cohort of 400 patients with FL, 15 patients (51.7%) therapy in patients with poor-risk DLBCL, including the elderly. We speculate presented with de novo tFL and 14 (48.2%) had known FL with median time to that the low rates of toxicity observed in our study may be due to sequential transformation of 6.7 years. Twenty (65.5%) patients were male with a median rather than concurrent administration of HD-MTX, and careful patient age at transformation of 54 years (range 27-72) and 80% had stage III/IV selection. Given the inherent limitations of this retrospective cohort study, disease at transformation. The median follow-up time from tFL diagnosis is 3.3 further prospective studies are warranted to validate this approach in poor- years. All patient received Rituximab - chemotherapy (R-CHOP or R-CHOP risk patients with DLBCL. like), with 11 patients (38%) requiring second line therapy to attain remission. Consolidation therapy algorithm was adapted based on age, performance status and donor availability. 16 patients (55%) were transplant eligible, 8 PB1842 patients (27.5%) received allogeneic SCT and 8 patients received autologous(A) SCT and 2 patients were allo-transplanted after relapsing post- TRANSFORMED FOLLICULAR LYMPHOMA TREATMENT OUTCOME ASCT . Thirteen (45%) patients were not SCT eligible and were consolidated DURING THE RITUXIMAB ERA 1 * 2 1 1 1 1 with either Zevalin 3 (10%) or Rituximab maintenance 8 (27.5) patients. The E Elhassadi , R Flavin , P Browne , P Hayden , L Higgins , E Vanderberghe median survival from transformation was 98 months with three deaths, (two 1Haematology Department , St. James’s Hospital, Trinity College Dublin, 2 from disease progression and one from transplant related mortality (Tables 1, Histopathology Department , St. James’s Department, Trinity College , Dublin, 2 and Figure 1). Ireland Summary and Conclusions: Compared to historical published data the median OS of 98 months in this small cohort of patients is encouraging and Background: Follicular lymphoma transformation (tFL) to Diffuse Large B Cell suggests that Rituximab therapy may have changed the natural history of tFL. lymphoma occurs in 16% to 60% of cases and is historically associated with a Fourteen of 16 patients transplanted remain alive and disease free and these median survival of less than 2 years and there are no prospective studies outcomes should be confirmed in a larger series. specifically evaluating treatment approaches in patients with tFL and there is little published data on the outcome of tFL in the Rituximab era. Aims: Retrospective study to evaluate treatment outcome of patients with tFL PB1843 diagnosed between 2003 and 2012 after adapting specific treatment algorithm. Methods: Patients diagnosed with tFL, between 2003 and 2012 identified from SECONDARY CNS INVOLVEMENT IN MALIGNANT LYMPHOMA: DATA the institutional lymphoma database were included. Data collected included FROM A PROSPECTIVE REGISTRY 1 1 2 3 4 age, gender, stage and prior treatment, interval to tFL diagnosis, IPI score and A Menssen , F Strehlow , R Schroers , U Schlegel , M Schmidt-Hieber , 5 6 7 8 9 tFL treatment. Only cases which fulfil the diagnostic criteria of DLBCL based P Reimer , F Griesinger , HG Höffkes , K Jordan , C Meyer zum Büschenfelde , 10 1 1 1 * on WHO criteria were evaluated. J Mezger , S Kreher , L Fischer , A Korfel , 1Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Charité - Universitätsmedizin Berlin, Berlin, 2Abteilung für Table 1. Patient clinical charateristics. Hämatologie und internistische Onkologie Knappschaftskrankenhaus, 3Klinik Male/Female 20/9 69/31% für Neurologie, Knappschaftskrankenhaus, Ruhr Universität Bochum, Bochum, 4 Median Age/yrs 51 Range (27-72) Klinik für Hämatologie, Onkologie und Tumorimmunologie, Helios Klinikum 5 Denovo tFLvsKnown FL 15 vs 14 52% vs 48% Berlin-Buch, Berlin, Klinik für Hämatologie, Internistische Onkologie und Stammzelltransplantation, Kliniken Essen-Süd, Essen, 6Pius-Hospital StageI,II vs III,IV 6/23 20/80% 7 BM invol. NegvsPos 16/5 55/17% Oldenburg , Klinik für Hämatologie und Onkologie, Oldenburg, Abteilung für Not available 8 Medizinische Onkologie, Radiologie Hämatologie, Palliativmedizin, Klinikum Fulda, Fulda, 8Abteilung für Hämatologie und Onkologie,, Universitätsklinikum R-IPI 0-2 vs 3-4 25/4 86/14 Halle, Halle, 9Abteilung für Hämatologie und internistische Onkologie, Asklepios B.Symptoms (+/-) 10/19 34.5/66.5% Klinik Altona, Hamburg, 10 Abteilung für Hämatologie und Onkologie , Relapse Disease (+/-) 11/18 38/62% St.Vincentius-Kliniken , Karlsruhe, Germany

Background: Secondary CNS involvement of malignant lymphoma (SCNSL) is extremely rare, and its optimal management is yet to be defined. In a Table 2. Consolidation treatment. prospective German registry we evaluated clinical characteristics, treatment tFL No % and outcome of patients diagnosed with SCNSL since July 2011. Rituximab Maintenance 8 27.5 Aims: Collection of data on diagnosis making and treatment strategies in Zevilan 3 10 SCNSL in the clinical routine. Auto-SCT 8 27.5 Methods: Patients with secondary CNS involvement of indolent or aggressive All0-SCT 8 27.5 non-Hodgkin`s lymphoma (confirmed histologically or cytologically) with or without systemic involvement at time point of CNS involvement were eligible. Both-SCT 27 Informed consent was obtained from all patients. Results: Data of the first 69 patients (median age 60 years, range 26-80) were analysed. Eight (12%) patients had simultaneous CNS and systemic involvement at first diagnosis (cohort I), and 61 (88%) had CNS involvement at relapse (cohort II), 11 (16%) of whom simultaneously had active systemic disease. Histology at first diagnosis was aggressive B-cell lymphoma in 48 (70%) and mantle-cell and T-cell lymphoma in 2 patients (3%) each; 17 patients (25%) had indolent B-cell lymphoma. Primary therapy in cohort II was R-CHOP in 35 patients (51%), CHOP in 9 (13%), R-CHOP/CHOP combined with other systemic chemotherapy in 8 (12%) and other systemic chemotherapy in 7 (10%). CNS prophylaxis was given to 10 (14%) patients: intrathecal (i.th.) chemotherapy alone in 3, high-dose methotrexate (HDMTX) intravenously alone in 3, whole-brain radiotherapy in 1 and a combination of those in 3; 2 patients (3%) have not received any anti- lymphoma therapy. Median time from first diagnosis to CNS relapse (cohort II) was 16 months. CNS lymphoma localisation was brain parenchyma in 39 patients (57%), meninges in 18 (26%), spinal cord in 2 (3%) and combination of those in 10 (14%). Therapy for CNS involvement was systemic chemotherapy in 37 patients (54%), systemic + i.th. chemotherapy in 30 (43%) and i.th. chemotherapy alone in 2 (3%). Systemic therapy was HDMTX-based in 62 patients (90%) and high-dose cytarabine-based in 36 (52%); high-dose chemotherapy with autologous stem-cell transplantation was given to 23 patients (33%). Median follow-up time from inclusion in the registry was 17 months. In cohort I, 3 patients progressed/relapsed after 7.0-11.5 months and one died after 16 months following diagnosis of CNS involvement. Median progression-free survival (PFS) and overall survival (OS) from CNS involvement in cohort II was 6.7 months (95%CI 3.7-9.5) and 15.7 months (95%CI 7.0-24.3), respectively. Median PFS Figure 1. Our institutional transformed follicular lymphoma treatment and OS of patients with parenchymal involvement were significantly longer (both algorithm. not reached) as compared to patients with meningeal involvement with 5.5

708 | haematologica | 2014; 99(s1) Milan, Italy, June 12 – 15, 2014

(95%CI 2.9-8.0) and 8.2 (95%CI 5.2-11.1) months, respectively (P<0.001 for PFS Background: Peripheral T-Cell Lymphoma (PTCL) is a group of lymphoid and 0.007 for OS). malignancies which has never been treated with any confidence as opposed Summary and Conclusions: With modern and systemically more potent anti- to its counterpart B-Cell Lymphomas. Despite the studies, which were lymphoma therapy the frequency of isolated CNS relapse seems higher than retrospective, the results in the majority of cases were disappointing, taking into previously reported reflecting reduced ability to clear the CNS as compared to consideration the aggressive clinical course of the disease, so survival did not systemic disease. Despite frequent use of CNS-penetrating systemic exceed 2 years in median. chemotherapy outcome of patients with SCNSL, particularly with meningeal Aims: To assess the response, progression free survival and overall survival involvement, remains poor. rates at 5 years using a new intensive combination chemotherapy Methods: Enrolled patients were diagnosed with PTCL, confirmed by a referenced pathologist, treated with the new chemotherapy ACEP X 6 PB1844 (Doxorubicine 75 mg/m² on day 1 + Cyclofosfamide 1200 mg/m² on day 1 + Etoposide 300 mg/m² on day 1 and Prednisolone 60 mg/m² from day 1 through SIGNIFICANT EFFECT OF RITUXIMAB MAINTENANCE IN FIRST LINE day 5) and Ifosfamide X 4 ( Ifosfamide 4 grams/m² on day 1 ) which were given TREATMENT IN MANTLE CELL LYMPHOMA after the completion of the first 6 cycles of ACEP . The study was performed at S Vokurka 1,* A Jungova 1, V Vozobulova 1, M Schutzova 1, P Jindra 1, D Lysak 1, M Hrabetova 1 Al-Bairouni University Hospital and the study was approved by the Syrian 1Haemato-Oncology, University Hospital in Pilsen, Plzen (Pilsen), Czech Republic Association of Clinical Oncology. 25 patients underwent the treatment. Most of them showed a complete Background: Mantle cell lymphoma (MCL) is a relatively rare malignancy with Results: unfavorable outcomes. Introduction of anti-CD20 rituximab maintenance (RM) response after the completion of the first six cycles (17/25) forming 68% of treatment into therapeutic protocols should be beneficial. patients, while another 5 patients became complete responders after the completion of treatment. Consequently, 22 patients are still living after 5 years, Aims: To verify the importance of rituximab maintenance in MCL first line with an overall survival rate of 88%, the study was updated in December 2013 treatment. and we still have 88% overall survival rate at 6 years. Methods: Prospective single center observation of newly diagnosed MCL (ACEP ) and Ifosfamide appears to be a good patients: n=57, median age 66 (47-82), 68% males, 84% Ann Arbor stage IV., Summary and Conclusions: choice in PTCLs, in light of the good response and overall survival rates, taking prognostic MIPI index media 6 (2-10), 92% R-CHOP-like and 8% R-COP into account the acceptable toxicity profile. However, a larger sample is needed induction therapy protocol, 46% intensified with Autologous stem cells to make it acceptable new combination chemotherapy for PTCLs patients. transplantation (SCT), 82% complete and 18% partial remissions prior to start of RM administration. Rituximab maintenance was administered as 375mg/m2 dose every 3 months for 2 years and the median number of administered doses was PB1846 7 (2-8), seven patients are still on treatment, eight patients discontinued the RM prematurely due to MCL relapse/progression, refusal of further treatment, or A RISK OF DERMOPATHY AND OPOTUNISTIC INFECTION AFTER health insurance company obstacles. Progression free survival (PFS, time since TREATMENT WITH ANTI-CCR4 FOR ADULT T-CELL diagnosis to relaps/progression ) was analyzed separately in a group of patients LEUKEMIA with and without Autologous SCT and in respect to RM administration. G Eguchi 1,* K Yamamoto 1, A Fukui 1, T Yamaguchi 1, Y Maeda 1 Results: In a group of non-intensified patients without Autologous SCT the 1Hematology, National Hospital Organization Osaka Minami Medical Center, probability of 2-years PFS and median PFS was 26% and 20 months if RM was Kawachinagano, Japan not given (n=16) versus 86% and median PFS not yet reached at the median follow-up of 37 (14-65) months if RM (n=15) was administered (p=0,01). In Background: Human T-cell leukemia virus type I (HTLV-I) is a human retrovirus Autologous SCT patients the probability of 2-years PFS and median PFS was that is an etiologic agent of adult T-cell leukemia/lymphoma (ATL/ATLL). The 75% and 46 months if RM was not given (n=12) versus 95% and median PFS poor outcome of adult ATL is mainly because of an intrinsic resistance of the not yet reached at the median follow-up of 50 (22-82) months if RM (n=14) was leukemic cells to conventional or high doses of chemotherapy and severe administered (p=0,02). No statistically significant differences were observed immunosuppression. The CC-chemokine receptor 4 (CCR4) is expressed in when comparing age, gender, MCL stage, MIPI index, complete remission almost ATLL cells. Thus, anti-CCR4 antibodies can be used as a treatment ratios prior to RM. RM administration was statistically significant predictor for strategy for ATLL. Mogamulizumab (MOG), which is a defucosylated anti-CCR4 prolonged PFS in the multivariable analysis (Figure 1). , showed good results even in patients with recurrent ATLL in phase I or II studies. MOG has strong antibody-dependent cellular cytotoxicity (ADCC). The common adverse events in the phase II study were infusion reaction and skin rashes. In our study, MOG inhibited the growth of ATL cells and induced remission. CCR4 is expressed not only in ATL cells but also in non- ATL regulatory T cells (Treg). After treatment with MOG, the population of Treg decreased significantly, which boosted the antitumor activity. MOG treatment was associated with the risk of viral infection as an opportunistic infection and skin disturbance (dermopathy). Aims: In the present study, we observe the effects of MOG as CCR4-specific ADCC against CCR4-positive ATL cells. However, CCR4 is not only on ATL cells but also on endogenous Treg. The decrease in the number of Treg after MOG monotherapy has been expected to boost the antitumor activity and to be involved in the development of immune disorders, including autoimmune diseases. On the other hand, we observed opportunistic viral infection including active CMV infection and skin disturbance associated with a rapid decrease in CD4+ T cells. Methods: In the present study, we treated 14 patients with ATL who were resistant to chemotherapy using MOG monotherapy, and we observed CCR4- Figure 1. specific ADCC against CCR4-positive ATL cells. In this study, CMV infection was detected using C7- horseradish peroxidase (C7-HRP) methods. Summary and Conclusions: Even though the numbers of our analyzed Results: All patients showed CR with a marked decrease in the number of ATL patients are small, we can observe that in newly diagnosed MCL patients cells. These results suggested that MOG was effective in chemotherapy-resistant responding to the initial induction therapy (R-CHOP-like, R-COP), the ATL patients. ATL cells were not found in her peripheral blood, and no administration of RM significantly prolongs PFS in both Autologous SCT treated rearrangement of TCRab gene was observed, which indicated molecular CR. patients and in those non-intensified. The data are not mature enough to asses Skin disturbance (dermopathy) was found 9 cases of 14 ATL patients treated the overall survival. with MOG monotherapy. The skin rash spread throughout her body with bulla and skin biopsy was performed, and diagnosed as Stevens–Johnson syndrome (SJS) in 2 patients of them. Administration of steroid and intravenous immunoglobulin PB1845 was performed, and SJS gradually improved. Further, In other patients, grade 2 and 3 dermopathy was found, and the patients was treated with glucocorticoid TREATMENT OF PERIPHERAL T-CELL LYMPHOMA WITH AN INTENSIVE steroid. CMV infection was detected using C7-HRP methods. CMV infection was PROTOCOL ACEP (ADRIAMYCIN,CYCLOPHOSFAMIDE,ETOPOSIDE AND diagnosed in 5 patients of 14 MOG treated ATL patinets. One of the patients died PREDNISOLONE) AND IFOSFAMIDE SHOWING AN IMPORTANT because of severe CMV infection despite of adequate treatment. OVERALL SURVIVAL AT 6 YEARS Summary and Conclusions: Thus, physicians should be aware of CMV infection M Salamoon 1,2, * M kenj 3 and development of immunocompromised condition after MOG monotherapy. 1medical oncology, 2hematology, al Bairouni university hospital, 3cytogenetics, Specific anti-CMV treatment for CMV reactivation should be recommended. kenj labs, damascus, Syrian Arab Republic Moreover, We have to find out the skin rash as soon as possible after treatment

haematologica | 2014; 99(s1) | 709 19 th Congress of the European Hematology Association with MOG and it should be recommended quick administeration with Results: Fifty-five kidney transplant recipients with PTLD were identified, at a glucocorticoid. Futher study for the dermopathy should be considered. median of 7.1 years since transplantation. Mean age at time of lymphoma was 54.4 years, 80% were men, and median follow-up time for all patients was ten months, and six years for patients alive at last follow up. Sixty percent had a PB1847 previous rejection, of whom 37% had been treated with ATG. Thirty-six percent of the lymphomas were nodal, 24% involved GI-tract, 18% CNS, and 21% HOW TO TREAT B-CELL LYMPHOMA, UNCLASSIFIABLE, WITH other organs. Sixty-seven per cent were Diffuse Large B-Cell Lymphomas, FEATURES INTERMEDIATE BETWEEN DIFFUSE LARGE B-CELL 11% were polymorphic PTLD and 14% were others. Thirty-seven patients died LYMPHOMA AND BURKITT LYMPHOMA. SINGLE CENTRE EXPERIENCE with a five year overall survival of 34% (Figure 1). J Michalka 1,* A Janikova 1, D Salek 1, Z Kral 1, J Mayer 1, M Moulis 2, L Kren 2 Summary and Conclusions: Post-transplant lymphoma disorder affects kidney 1Department of Internal Medicine, Hematology and Oncology, University transplant recipients after several years with heterogenous clinical manifestations. Hospital Brno and Masaryk University, School of Medicine, Brno, 2Department PTLD is strongly associated with previous treatment for graft rejection. Early of Pathology, FN Brno, Brno, Czech Republic death was more common than what is seen in non-PTLD lymphomas, probably B-cell lymphoma, unclassifiable, with features intermediate Background: due to co-morbidity and increased infectious complication. Better supportive care between diffuse large B-cell lymphoma and Burkitt lymphoma (DLBCL/BL) is and an individualized treatment approach seems important. a separate entity in the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues 2008. It is nowadays a provisional category of a spectrum of features between two borderline lymphomas – difusse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). These lymphomas have morphological and genetic features of both DLBCL and BL, so they cannot be clearly included in either one of those two entities. DLBCL/BL generally has an agressive clinical course and no guidelines for treatment are available yet. Aims: To compare efficacy of different treatment options. Methods: Retrospectively we reviewed clinical data from our institution’s register between years 2010-2013. Subsequently we analysed therapy outcome due to chosen regimens. The treatment strategy decision was made depending on patient’s age, clinical stage of the disease and the IPI score. All of the histology samples were reviewed by experienced pathologists, in majority of the cases including FISH and genetic abnormalities diagnostic tests. Results: Since January 2010 to December 2013 we registered 30 patients with newly diagnosed DLBCL/BL, constituting approximately 3.4% of all non- Hodgkin lymphomas (n=881). For comparison, in the same time period, we registered 301 cases of DLBCL (34%) and 16 cases of BL (1.8%). There were 14 men and 16 women, average age being 65 years (38-86y). One patient (86y) was treated by paliative radiotherapy only and died within 1 month due to lymphoma progression. 10/30 patients (33%), average age 53y (38-66y), clinical stage I-IV, average IPI score 3 (0-5), median LDH 5.27 µkat/l (2.79-107), were treated with intensive approach, when R-CHOP treatment was enhanced with 3-4 cycles R-CODOX-M with or without R-IVAC up to 5-7 chemotherapy Figure 1. cycles total. Two patients from this group died, one (53y) had confirmed concurrent BCL2-IGH and MYC rearrangement (double-hit lymphoma), was primarily chemoresistant, and died within 4 months from diagnosis due to lymphoma progression. The second one (60y) died due to treatment toxicity and PB1849 concurrent illness (sepsis and ischemic cerebral stroke) immediately after DEPO-ITV: A NEW SCENARIO WITH INTRATHECAL AND INTRAVENOUS treatment completion. The remaining 8 patients (80%) from a group of DEXAMETASONE TO PREVENT CHEMICAL ARACHNOIDITIS RELATED intensively treated are nowadays in complete remission lasting 3-31 months WITH LIPOSOMAL CYTARABINE depending on the treatment completion date. 19/30 patients (63%), average A De La Fuente 1,* M Olave 2, FJ Peñalver 3, M Estévez 1, L Arango Rial 4, age 71y (57-86y), clinical stage I-IV, average IPI score 3 (0-5), median LDH 4.99 P Martinez Barranco 3, L Villalón 3, S Solórzano 1, R Iglesias 1, C Montalván 1, µkat/l (2.5-40.14), got usual R-CHOP based chemotherapy, in 9 cases (47%) R de Oña 1 including 1-2 cycles of high dose methotrexate or high dose cytarabine finally. 1Hematology, MD Anderson CC Madrid Spain, Madrid, 2Hematology, H.C.U. 3 patients (16%) from this group died during the treatment or within 6 months Lozano Blesa, zaragoza, 3Hematology, H. Fundacion Alcorcon, 4Hematology, after treatment completion due to lymphoma progression. 3 patients (16%) H.C.U. Lozano Blesa, Madrid, Spain from this group relapsed within one year and recieved another chemotherapy regimens. 13 patients (68%) from this group are in complete remission or the Background: Intrathecal Liposomal Cytarabine (LC) is FDA/EMA approved for treatment is nowadays still ongoing. We haven’t evaluated the disease free Lymphomatous Meningitis (LM) treatment. Retrospective studies have evaluated survival (DFS) and overall survival (OS) yet, because of short follow-up. LC in LM prophylaxis. Chemical arachnoiditis (headache, nausea, vomiting and Despite short follow-up, our data suggest that Summary and Conclusions: high temperature) is the most common related adverse effect (25-40%). Steroids R-CHOP based chemotherapy is less effective than it’s combination with co-administration, intrathecal and/or systemic, is suggested to prevent this intensive regimens containing R-CODOX-M and R-IVAC. The most important adverse event but there is no consensus about the best pattern of use. factor that influenced the treatment strategy was patients’ age. For setting the The aim of this study is to evaluate the incidence of chemical proper treatment guidelines bigger patients cohorts and a longer follow up of Aims: arachnoiditis in patients with hematologic malignances and high risk of LM, the survivals are required. treated with the new Depo-ITV (LC 50 mg IT + Dexametasone 4 mg IT + Dexametasone 20 mg iv, day 1) as LM prophylaxis. Methods: We carried out a study on 3 different sites to analyze the toxic profile PB1848 and the effectiveness of Depo-ITV. Inclusion criteria were as follows: patients≥ POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER AFTER 18 at the time of treatment, confirmed diagnosis of hematologic malignance, KIDNEY TRANSPLANTATION treated with Depo-ITV as LM prophylaxis in the period 1 st January 2010 to 1 st I Fiskvik 1,* Ø Bentdal 2, H Holdaas 2, T Leivestad 2, T Grotmol 3, H Holte 1 January 2014. Exclusion criteria: previous lymphomatous or infectious meningitis, 1Norwegian Radium Hospital, 2Department of Transplant Medicine, Oslo previous neurological toxicity related to systemic chemotherapy. Depo-ITV toxic University Hospital, 3Norwegian Cancer Registry, Oslo, Norway profile was evaluated as CTCAE v3.0 of NCI scale . We also recorded demographic and clinical data, systemic treatment, systemic response, and LM Background: Post-transplant lymphoproliferative disorder (PTLD) is a incidence. This study has been approved by local ethics committees. heterogeneous group of lymphoid lesions. Although rare, it is an important Results: One hundred twelve administrations of Depo-ITV in 54 pt, median per long-term complication in kidney transplant recipients. pt 2 (1-5), were analyzed during the above-mentioned period. Baseline Aims: To describe demographics and prognosis in a cohort of PTLD patients. characteristics median age 55 (20-79), M/F 32/22, histologic subtype; DLBCL 25 Methods: The Norwegian Nephrology Registry has a complete data set for pt, Lymphoblastic Leukemia 13 pt, Follicular Lymphoma 4 pt, Myeloblastic renal recipients since 1969. The register was linked to the Norwegian Cancer Leukemia 4 pt, MCL 2 pt, Richter 2 pt, Burkitt 2 pt, T cell lymphoma 2 pt. HiDAC Registry of Norway to identify cases of PTLD. Clinical data were retrieved from occurred in 1 case, high dose methotrexate in 4 cases and HiDAC plus high local hospitals. Demographic data, transplant history, outcomes and pathology dose systemic methotrexate in 19 cases. Toxicity: There were 3 pt with grade 3 were characterized using SPSS statistics. (no grade 4) AE, 4 (3.5%) cases out of 112 administrations, and the cases were

710 | haematologica | 2014; 99(s1) Milan, Italy, June 12 – 15, 2014 as follows: Case 1: 70 year old female diagnosed with DLBCL treated with 2 from time to time. Whether elevated BM prolymphocytes, serving as a surrogate Depo-ITV administrations, after 1st administration grade 3 orthostatic headaches of host immunity, can predict prognosis of DLBCL patients remains unknown. occurred, but the orthostatic characteristic the headache was also considered Aims: To explore whether elevated BM prolymphocytes serving as a surrogate depo-ITV related. A second administration of Depo-ITV (no dose reduction) was of host immunity, could predict prognosis of DLBCL patients. performed without AE. Case 2: 41 year old male, Richter, headache grade 3 after Methods: Two hundred and ten de novo DLBCL patients from 2001 to 2012 1st Depo-ITV admintration. Treatment was discontinued. Case 3: Lymphoblastic were retrospectively analyzed in the present study. Leukemia, systemic HiDAC and 4 depo-ITV administrations. Headache grade 3 Results: Elevated BM prolymphocytes with normal cytomorphology (>1.5%) after 2nd and 4th administrations (no dose reduction after 2nd). Sings of could be found in 18 DLBCL patients (8.6%). There was no significant difference intracranial hypertension occurred after 4th Depo-ITV. This toxicity was reversible. in gender, age, B symptoms, performance status, LDH, stage and IPI score Systemic responses were as follows: CR 41, PR4, progression disease 7 and 2 between patients with elevated BM prolymphocytes versus all the remaining non evaluated patients. With 10.4 (0.5-49) month median follow up, we report no cases ( p>0.05). Patients with elevated BM prolymphocytes showed significantly cases of LM, 37 pt are alive and in CR, 13 pt are dead (10 p disease progression), superior OS and PFS compared with all the remaining patients ( p=0.031 and 3 pt are currently in active treatment and 1 case is lost for follow up. p=0.043, respectively), especially in those high-risk patients ( p=0.041and Summary and Conclusions: Depo-ITV reduces the incidence of post LC p=0.027, respectively). Of 40 patients with BM involvement (BMI), 20 had chemical arachnoiditis and is effective in preventing LM. The Depo-ITV pattern concordant BMI and 20 had discordant BMI. Concordant BMI had significantly suggested here ensures chemical arachnoiditis prevention in contrast to the shorter OS and PFS than uninvolved BM patients ( p<0.001and p=0.005, multiple day steroids patterns. respectively), whereas discordant BMI did not ( p=0.390 and p=0.918, respectively). Multivariate analysis revealed elevated BM prolymphocytes remained a favorable factor for PFS (RR, 0.130; 95% CI, 0.018-0.950, p=0.044), PB1850 but not for OS. However, concordant BMI was an unfavorable predictor for OS (RR, 2.474; 95% CI, 1.138-5.377, p=0.022, respectively), but not for PFS. HIGH-DOSE CYTARABINE AND ±RITUXIMAB FOR Summary and Conclusions: Elevated BM prolymphocytes at diagnosis may COLLECTION OF PERIPHERAL BLOOD STEM CELLS IN HIGH-GRADE imply a good prognosis, allowing the identification of a superior outcome NON-HODGKINS´ LYMPHOMA. SINGLE CENTER EXPERIENCE WITH subgroup in high-risk DLBCL patients. Concordant BMI has a negative impact FILGRASTIM BIOSIMILARS. on survival in DLBCL patients. I Skoumalová 1,* Z Kapitáňová 1, R Urbanová 1, E Faber 1, Z Pikalová 1, T Papajík 1, K Indrák 1 1 Department of Hemato-Oncology, Faculty Hospital Olomouc, Olomouc, Czech PB1852 Republic PROGNOSIS FACTORS IN ELDERLY PATIENTS WITH PRIMARY CNS Background: For the patients with aggressive non-Hodgkins´ lymphomas LYMPHOMA TREATED WITH NONRADIATION, INTERMEDIATE-DOSE (NHL) chemotherapy – high-dose of cytarabine with mitoxantrone ±rituximab METHOTREXATE-CONTAINING REGIMEN (R±HAM) is used for the standard collection of peripheral blood stem cells at SY Lee 1, Y Okoshi 1, N Kurita 1, M Seki 1, Y Yokoyama 1, K Maie 1, Y Hasegawa 1, our Department as a part of Sequential Protocol chemotherapy (2xPACEBO, S Chiba 1,* IVAM, PACEBO, HAM ±rituximab). 1Department of hematology, University of Tsukuba , Tsukuba, Japan Aims: We describe here the experience with the efficacy and safety together with the comparison of two filgrastim (G-CSF) biosimilars. Background: Nearly half of all patients with primary central nervous system Methods: R±HAM was given as follows: rituximab 375 mg/m 2 on day 1; lymphoma (PCNSL) are known to be aged over 60 years. However, clinical cytarabine 2g/m 2 in 4 doses on day 1 and 2; mitoxantrone 10 mg/m 2 in 2 doses factors affecting treatment outcomes in elderly patients are understudied. on day 2 and 3. In patients with age over 60 the dose of cytarabine and Aims: In this study,we intended to identify prognosis factors in elderly patients mitoxantrone was reduced to 0.5 g/m 2 and 7 mg/m 2, respectively. Three with PCNSL treated with nonradiation, intermediate-dose methotrexate (MTX)- different types of G-CSF at the same dosage (10 μg/kg of body weight) were containing regimen. used to stimulate peripheral blood stem cells: Neupogen (39 patients), Zarzio Methods: We analyzed 38 patients with PCNSL older than 60 years. All patients (28 patients) and Tevagrastim (11 patients). Retrospective analysis was were treated with nonradiation, intermediate-dose MTX-containing protocol performed in cohort of 78 patients with NHL in the period January 2009 - comprising an induction therapy and maintenance therapy between March 2005 September 2013. Median of age was 53 (22-64) years. and May 2013 at the University of Tsukuba Hospital. As an induction therapy, 1 2 2 Efficacy of the type of G-CSF in terms of the leucopheresis number (collection g/m intravenous (i.v.) MTX was given on days 1, 10, and 20; 40 mg/m i.v. 2 days) and number of CD34+ cells per kg collected was the first goal of our study. ranimustine, on day 1; 60 mg/m oral , from days 1 to 7; and i.v. or 2 The incidence of infections and other side-effects were recorded in addition. oral methylprednisolone, at a dose of 120 mg/m every other day from days 1 to 2 Kruskal-Wallis and Fisher exact tests were used for comparison. 20 and then at a dose of 60 mg/m from days 21 to 45. Fifteen milligrams of MTX There were no differences among the groups of patients with respect and 40 mg of cytarabine were injected intrathecally (i.t.) on days 1, 5, 10, and 15 Results: 2 to the gender, age, marrow involvement and previous treatment. There were with leucovorin rescue. As a maintenance chemotherapy, 1 g/m i.v. MTX was 2 2 no statistically significant differences in number of collection procedures among given on day 1; 40 mg/ m i.v ranimustine, on day 1; and 60 mg/m oral the groups (p=0.084); on average 1.69 procedures for Neupogen, 1.53 procarbazine, from days 1 to 7; and 15 mg i.t. MTX and 40 mg i.t. cytarabine on procedures for Zarzio and 1.81 procedures for Tevagrastim. Also there were no day 1. Patients who achieved a complete remission or partial remission after 1 statistically significant differences in number of CD34+ cells per kg collected course of induction chemotherapy proceeded to further therapy with 5 courses of (p=0.497); on average 8.29x10 6 CD34+ cells per kg for Neupogen 8.51x10 6 maintenance chemotherapy every 6 weeks. When progressive disease was CD34+ cells per kg for Zarzio and 6.66x10 6 CD34+ cells per kg for Tevagrastim. documented, the protocol was stopped. Overall survival (OS) was calculated from Patients hospitalized and central venous line inserted for the whole period of the first date of the induction chemotherapy to the date of any cause of death. the priming (42 patients) have a significant higher risk of septicaemia (p=0.002). Progression free survival (PFS) was defined as the period from the first date of the Patients who proceed to the transplantation engrafted in all cases. induction chemotherapy to the first date of the documentation of disease Summary and Conclusions: R±HAM is well tolerated and highly efficient priming progression or death as a result of PCNSL. The OS and PFS were estimated with chemotherapy (average number of CD34+ cells collected was 7,82x10 6 per kg, the Kaplan-Meier method. Univariate analysis to see impact of clinical factors on 78 patients). Different types of G-CSF show no statistically significant differences OS or PFS was performed with the log-rank test. Independent predictive factors in the stimulation efficacy. Prolonged hospitalization and central venous for OS were analyzed by Cox proportional hazards regression model. catheterization is associated with higher risk of septic complications. More patients Results: Twenty-four patients were able to finish the full protocol. Three-year should be analysed in order to further increase the validity of results. OS and PFS rates were 56.2% [95% confidence interval (CI): 36.2%>76.2%] Supported by the grants MSM-6198959205 and IGA UP LF-2013-004. and 29.8% (95% CI: 9%>50.6%), respectively, with a median follow-up of 36.5 months. We found age > 75 years, Karnofsky performance score<70, altered mentation, and creatinine clearance (CrCl) > 90 ml min -1 were significant PB1851 (p< 0.05) factors associated with a worse survival by univariate analysis. The only parameter significantly associated with PFS was altered mentation with ELEVATED BONE MARROW PROLYMPHOCYTES PREDICT SUPERIOR univariate analysis (p=0.024). Although patients with CrCl > 90 ml min -1 showed OUTCOME IN DIFFUSE LARGE B CELL LYMPHOMA tendency toward worse PFS, it was statistically insignificant (p=0.118). R Feng 1,* X Wei 1, Y Wei 1, F Huang 1, M Xie 1, H Jing 1, X Hao 1, R Lin 1, X Xu 1, Multivariate analysis revealed CrCl [ p<0.05; hazard ratio (HR) = 3.39; 95% CI, D Fang 1 1.08–10.68] and altered mentation ( p<0.05; HR = 6.27; 95%CI, 1.37–28.83) 1Department of Hematology, Nanfang Hospital, Southern Medical University, were independently significantly associated factors with OS. The most frequent Guangzhou, China adverse effect was myelosuppression, with grade 3 to 4 hematologic toxicities in 28 patients. Grade 3 to 4 hepatic toxicity was observed in 6 patients. Renal Background: Elevated prolymphocytes with normal cytomorphology can be seen toxicity was documented in 13 patients, 5 of whom required dose reduction or in bone marrow (BM) of patients with diffuse large B-cell lymphoma (DLBCL) modification of the protocol. No delayed neurotoxicities were observed.

haematologica | 2014; 99(s1) | 711 19 th Congress of the European Hematology Association

Summary and Conclusions: More aggressive therapy may be introduced in newly diagnosed poor prognosis DLBCL were treated with 6 cycles of two-weekly selected patients with poor prognosis factors to improve outcomes. DA-EDOCH14-R. These patients were treated with DPA s.c and blood transfusions according to usual clinical practice. Initial DPA dose: 150mcg/week. Increase dose DPA to 300 mcg/week if no response is seen in 6 weeks’ time. We stopped DPA PB1853 when response is seen, used to be 4 weeks after QT. We analyze these risk factors: HBP, DM, DL, smoke, CVC, steroids, cancer, obesity and age >60. ROLE OF FDG-PET SCANS IN THE MANAGEMENT OF PEDIATRIC NON- Results: We administered DPA at 25 patients (96%) for anaemia: 14(56%) HODGKIN’S LYMPHOMA. CCHE EXPERIENCE Hb>11gr/dl, 10 (40%) Hb 9-11gr/dl and 1(4%) Hb<9. Median Hb when we H Abdelrahman 1,* A Hamoda 1, M Sedky 2, E Moussa 3, I Attiya 1, A Youssef 4, 4 5 6 7 initiated treatment of DPA: 11.4gr/dL. 18 patients (72%) started DPA within the T Raafat , W Omar , O Hassanein , A El Haddad first two months of treatment. Duration treatment median: 3 months. The dose 1Pediatric Oncology, National Cancer Institute, 2Pediatric Oncology, National 3 4 was increased in 5 patients (20%). High incidence of DVP (24% patients) was Research Center, Pediatric Oncology, Elmenufeya University, Radiodiagnosis, distributed as follows: 2 VTE, 1 DVP left axillar, 1 DVP femoral popliteal, 1 5Nuclear Medicine, National Cancer Institute, 6Clinical Reserch, Children Cancer 7 mammary and jugular left vein, 1 DVP basilica left vein. No relationship was Hospital Egypt, National Cancer Institute, Cairo , Egypt observed between VTE and high Hb level (median Hb: 10.1gr/dl (patients with VTE) vs 10gr/dl (patients without VTE), or with risk factors (median: 5(with Background: Malignant lymphomas are the third most common malignancy TEV) vs 4(without TEV)). At a median follow up of 40.5 months, 3-year among children and adolescents, with a propensity for widespread dissemination. progression-free was estimated and overall survival was 85%. 18-F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) is a Summary and Conclusions: Our data suggest that the use of DPA is noninvasive, 3-dimensional imaging modality that has become widely used in the associated with a low rate of transfusion, but a high incidence of VTE. ESAs management of patients with malignant lymphomas. PET is the most important don’t seem to worse progression-free survival in patients treated with recent advance in noninvasive lymphoma assessment. Current applications of 14DA.EDOCH. ESAs recommendations should be followed in order to minimize PET in lymphoma may be divided into pretreatment staging, restaging, therapy thrombotic disease. monitoring and post therapy surveillance. Evaluation of residual masses and the recommendation to document them histologically before intensifying treatment in cases of incomplete remission is one of the difficulties during patients’ treatment. PB1855 Usefulness of PET scanning to assess viability of a residual mass is under evaluation in childhood lymphoma with the hope that it might replace histologic A REVIEW OF HIGH GRADE NON-HODGKIN LYMPHOMA CARE IN A documentation, but this evaluation is less advanced than in adult. UNIVERSITY HOSPITAL GROUP IN IRELAND Aims: To evaluate the sensitivity, specificity and predictive values of PET scan MP Crowley 1,2, * R Crotty 3, MR Cahill 1, CG Murphy 4, J O’Keeffe 4, BR Bird 4 during management of pediatric Non-Hodgkin’s lymphoma. Correlation of PET 1Haematology, Cork University Hospital, 2HRB Clinical Research Facility, results with conventional CT, the patients’ clinical outcome, and its impact on 3School of Medicine, University College Cork, 4Medical Oncology, Bon Secours the treating physician decision was done. Hospital, Cork, Ireland Methods: A retrospective study enrolled on pediatric patients with NHL at Children Cancer Hospital of Egypt (CCHE) during the period from July 2007 till Background: High-grade non-Hodgkin lymphoma (NHL) is an aggressive end of June 2013 was done. Inclusion criteria included the diagnosis of mature malignancy that requires urgent, intensive management. It is estimated that B cell NHL, for whom PET - in addition to conventional CT scan- was done at 60% of patients are cured (Cancer Research UK) so rapid diagnosis and any stage of the treatment. Blind revision of all PET and CT scans was commencement of chemotherapy are crucial to ensure the best possible specifically done for this study. outcomes. Clinical practice guidelines are systematically developed statements Results: For 115 pediatric NHL patients, 152 PET and 152 CT scan were done. designed to assist practitioners and patients in making decisions about Median age was 5.7 years (range 1-18 years). They were 85 males (74%) and appropriate healthcare for specific clinical circumstances. However, there 30 females (26%). One hundred twenty six scans (82.9%) were done for 100 remains a significant variation in the utility of recommended treatments in Burkitt lymphoma patients, while 26 scan (17.1%) done for 15 DLBC. Nineteen Lymphoma (Loberiza et al Leuk Lymphoma 2014). examination (12.5%) were done before starting chemotherapy, 107 (70.3%) at Aims: In Ireland, data is lacking on how closely non-Hodgkin lymphoma time of evaluation while 26 (17.1%) during Follow up. For all patients, sensitivity management follows guidelines. This study is the first to address this issue. was 91.6% for PET, while was 70.0% for conventional CT (p=0.02). Specificity Methods: The study was carried out in two university affiliated hospitals in was 84.1% for PET and 58.9% for CT (p< 0.001). PPV for PET was 50%, while Ireland. 125 consecutive high-grade non-Hodgkin lymphoma patients were was 22% for CT scan (p<0.001). NPV for PET was 98%, while was 92% for CT identified from the National Cancer Registry of Ireland. Appropriate quality (p=0.01). In burkitt lymphoma; sensitivity of PET was 91.6%, while was 66.6% markers were chosen (Wennekes et al, J Clin Oncol 2011) and, in keeping with for CT (p=0.08). Specificity was 82.4% and 57.8% for PET and CT respectively previous research, 90% adherence was set as the target. Data was obtained (p=<0.001 ), while PPV and NPV were 35.4%, 14.2, 98.9%, 94.2% for PET and through a systematic retrospective chart analysis of paper and electronic records. conventional CT (p= 0.0005 ) (p=0.05) respectively. In DLBCL patients; Results: Analysis focused on three areas – diagnosis and staging, treatment, sensitivity was 85.7% and71.4% for PET and CT respectively (p value=0.31). and organization of care. Diagnosis and staging markers were generally well Specificity was 89.4%, 57.8% for PET and CT (p =0.05 ). PPV and NPV were adhered to. 92% of patients were diagnosed with an appropriate biopsy, and 75%, 38.4%, 94.4%, 84.6% for PET and CT (p =0.02) (p =0.18) respectively. 98% of patients had appropriate blood tests performed. However, adherence Summary and Conclusions: PET scan is significantly more sensitive than rates for treatment and organization of care markers were much lower. 85% of conventional CT in the management of aggressive mature B cell pediatric NHL. patients received a DA-CHOP-R or DA-EPOCH-R regimen, and 75% of patients received a histological diagnosis within the 21 day target period. Chemotherapy was commenced within 28 days of diagnosis in 83% of patients. PB1854 Adherence rates for the recording of standardized information were particularly low. 54% of patients had an International Prognostic Index (IPI) score recorded. EFFICACY AND SAFETY OF DARBEPOETIN-ALFA IN POOR PROGNOSIS Use of the Cheson criteria to report treatment response was minimal. DIFFUSE LARGE B LYMPHOMA CELLS PATIENTS TREATED WHIT TWO- Summary and Conclusions: These results are in keeping with previously WEEKLY DA-EDOCH14 1 * 1 1 1 published studies . Management guidelines are being met in 8 of 21 areas. E Flores Ballester , J Garcia Suarez , M Callejas , E Magro Mazo , Although guideline adherence rates are similar to international data, more needs JJ Gil Fernandez 1, Y Martín 1, M Lopez Rubio 1, MA Calero 1, T Pascual 1, 1 1 1 1 1 1 to be done to achieve optimal standards of care. Follow-up investigations post- F Perera , M Cortti , C Casco , S Marcellini , L Juarez , I Gutierrez , C chemotherapy need to be carried out in a higher proportion of Burgaleta 1 1 patients. Standardised information such as IPI and stage needs to Hospital Universitario Príncipe De Asturias, Alcala De Henares, Madrid, Spain be documented so that patients can be appropriately risk-stratified and treated according to the most up to date evidence. It is also important to document Background: Erythropoiesis-stimulating agents (ESAs) raised safety concerns the severity of disease being treated in an institution. Given that some criteria are about decreased overall survival (when used to maintain Hb>12 gr/dl) and rarely applied, there is a question about their practicality in clinical practice. increased venous thromboembolic (VTE) events in cancer patients. The impact of these agents has not been studied in aggressive lymphomas treated with dose-dense immunochemotherapy regimens, a strategy that triplicate the risk PB1856 of anaemia and transfusion. (Leuk Lymphoma 2011;52:996). Aims: The aim of the present study was to evaluate the efficacy and safety of DIAGNOSIS AND CLINICAL OUTCOME OF 9 CASES OF darbepoetin alpha (DPA) in a prospective phase 2 study, single centre, of poor NEUROLYMPHOMATOSIS; SINGLE INSTITUTIONAL EXPERIENCE OVER prognosis (aaIPI 2-3) diffuse large B-cell lymphoma (DLBCL) treated with the THE 7 YEARS modern infusional regimen DA-EDOCH14-R. (Br J Haematol. 2013 M Fujisawa 1,* Y Suehara 1, K Seike 1, K Fukumoto 1, M Fukaya 1, H Sugihara 1, Feb;160(4):510-4). Y Nishida 1, M Takeuchi 1, K Matsue 1 Methods: From 2008 to 2013, 26 patients (median age 56 years; range 18-70) 1Hematology/Oncology, Kameda Medical Center, Kamogawa city, Japan

712 | haematologica | 2014; 99(s1) Milan, Italy, June 12 – 15, 2014

Background: Neurolymphomatosis (NL) is an extremely rare neurologic uncertain significance. The reports were not centrally reviewed. The patients’ manifestation of no-Hodgkin lymphoma (NHL) in which peripheral nerve clinical course was interrogated for the presence of disease recurrence, results infiltration of lymphoma cell is a dominant feature in both clinically and of subsequent FDG-PET scans, whether a biopsy of the area was performed pathologically. We previously reported a high frequency of NL as a relapse as well as results of any ancillary investigations or review by other specialists. disease of intravascular large B cell lymphoma (IVL), although NL could be Results: There were 42 patients (M:F 1.3:1) with a median age of 51 (range presented as an initial disease as well as relapsed disease in other types of 20-76). The scans were performed at end of treatment and at varying time NHL. In addition, the clinical features and treatment outcomes of NL is largely points thereafter. 23% of PET-CT performed were equivocal (80 scans from the unknown. However, recent enthusiastic use of PET/CT in lymphoma has 347 end of lymphoma treatment PET-CT scans performed at NPH). Histologies facilitated the diagnosis of NL. included Hodgkin lymphoma (15), diffuse large B-cell lymphoma (15), Burkitt Aims: In this paper, we updated our experience on NL at our hospital over the lymphoma (5), and primary mediastinal B-cell lymphoma (2). After a median period of January 2007 to February 2014. follow up of 21 months, 34 of 42 patients with persistent uptake at the end of Methods: We reviewed the clinical records at the Hematology/Oncology treatment were alive and disease free. Five patients had died, only one from Department of Kameda Medical Center. The diagnosis of NL required the 1) lymphoma. Seven patients had relapsed (five confirmed by biopsy) and all clinical symptoms and neurological examination findings referable to the cranial seven received salvage chemotherapy. Fifteen of 42 patients in this group or spinal nerves, and 2) histological confirmation of malignant lymphoma cells underwent biopsy- five had confirmed disease. Other biopsy results included within the peripheral nerve, nerve root/plexus, or cranial nerve or 3) CT/MRI inflammatory or necrotic tissue, solid organ malignancy, tuberculosis and a demonstration of nerve enhancement and/or enlargement of peripheral nerve(s) mycetoma. Of the patients who did not undergo a biopsy, serial FDG-PET or nerve root that were also demonstrated by the accumulation of FDG by FDG- scanning (median 1 further scan, range 1-5) or additional studies such as MRI PET/CT. Patients with stomach limited mucosa associated lymphoid tissue or high resolution CT-scanning suggested the following diagnoses: post- (MALT) lymphoma and leukemic infiltration of peripheral nerve due to acute treatment inflammatory change (21 patients), thymic rebound (3) and pulmonary were excluded from the study. infection (3). Results: Over the past 7 years, there were 581 patients diagnosed as a NHL Summary and Conclusions: The finding of persistent low-grade uptake on except for mucosa associated lymphoid tissue (MALT) lymphoma of stomach. end-of treatment FDG-PET is not an uncommon finding in our MDT meetings. Among them, we identified 9 cases (1.55%) diagnosed as having NL. The In our series of patients, treated with curative intent, the majority of patients with patients consisted of 2 men and 7 women with median age of 72 years (range; positive but indeterminate findings did not have a clinical course consistent 63-83 years). NL occurred as a part of presenting disease in 2 patients and as with persistent disease. The non-specific nature of FDG underlines the a relapse disease in remaining 7. Four patients were presented NL as a relapse importance of careful review of patients with persistent low-grade uptake at the disease of intravascular large B-cell lymphoma (IVL), 3 patients were as a end of treatment, especially where decisions about further toxic therapies are concomitant extranodal lymphoma (stomach, ileum, and uterus), and 2 were as made. We recommend a biopsy prior to further therapy wherever possible. For a relapse disease of nodal DLBCL. IVL patients showed significantly higher patients unable to undergo biopsy we suggest a team based approach that frequency in the development of NL compare to non-IVL patients (4/14 vs 5/567, considers alternative causes coupled with follow-up scanning. Our study is p=0.004). CD5 was positive in 8 cases. Diagnosis of NL was made by limited by the fact that a range of lymphoma subtypes and different disease neurological findings, enlargement and enhancement of affected cranial or stages have been included. peripheral nerves by MRI, and FDG-uptake of affected nerve demonstrated by *FA and SZ contributed equally to the work. PET/CT in all of the patients. Autopsy also confirmed the lymphoma infiltration in one patient. Affected nerve included lumbosacral nerve (4 cases), peroneal nerve (1 case), cranial nerves (2 cases). Cerebrospinal fluid cytology was PB1858 positive in 4 cases (44%). Six patients developed CNS involvement subsequently. Eight patients received high dose methotrexate (MTX) containing FIRST-IN-MAN STUDY OF 4SC-202, A NOVEL ORAL HDAC INHIBITOR IN treatment in addition to systemic chemotherapy, and 4 patients additionally PATIENTS WITH ADVANCED HEMATOLOGICAL MALIGNANCIES; (TOPAS received but only 2 patients responded. Four patients additionally received STUDY) 1 * 2 2 2 1 involved nerve irradiation and all of them responded transciently. Five patients B von Tresckow , ME Goebeler , C Sayehli , S Gundermann , D Eichenauer , 3 3 4 4 1 5 5 died due to NL with median of 5.1 months after NL development and 3 patients W Aulitzky , L Bacchus , S Igel , M Schwab , S Sasse , B Hauns , A Mais , 5 5 5 5 5 5 still receiving chemotherapy and irradiation. B Hentsch , H Kohlhof , R Krauss , B Krauss , R Baumgartner , D Vitt , A 1 NL is a challenging disease with respect to both Engert Summary and Conclusions: 1 2 diagnosis and treatment, but careful neurologic examination and contemporary University Hospital Cologne, Cologne, University Hospital of Wuerzburg, 3 4 imaging technique especially PET/CT often detect relevant neural involvement. Wuerzburg, Robert Bosch Hospital, Dr. Margarte Fischer-Bosch Institute of 5 Although most effective regimen remained undetermined, high dose MTX Clinical Pharmacology, Stuttgart, 4SC AG, Planegg-Martinsried, Germany combined with systemic chemotherapy might benefit in a subset patients. Background: 4SC-202 is a specific inhibitor of protein deacetylases HDAC1, 2 and 3 and lysine specific demethylase LSD1 (KDM1A). Enzymatic inhibition PB1857 leads to transcriptional repression of Wnt and Hedgehog signaling. 4SC-202 provokes the inhibition of stemness-related properties of cancer cells and THE SIGNIFICANCE AND OUTCOME OF THE FINDING OF PERSISTENT affects their viability. LOW GRADE UPTAKE ON FUNCTIONAL IMAGING USING 18F- Aims: Patients with advanced hematological malignancies including AML, ALL, FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY (FDG- CLL, MM, MDS or lymphoma were orally dosed either once daily (QD) or twice PET) IN LYMPHOMA PATIENTS daily (BID) from days 1 to 14, or BID continuously, in a 21-day cycle. Dose F Alwan 1,* S Zemenides 2,3, D Hughes 1, K Cwynarski 1, A Martin 4, T Wagner 5, escalation followed a 3+3 design. Study objectives include safety, tolerability C Kyriakou 2, C McNamara 1 and pharmacokinetics (PK), determination of MTD and DLT as well as 1Department of Haematology, Royal Free Hospital, 2Department of optimization of dosing. Biomarker program includes measuring of HDAC Haematology, Northwick Park Hospital, 3National Institute of Health Research, inhibition, total lysine acetylation and gene expression profiling. Additionally, the 4Department of Radiology, Northwick Park Hospital, 5Department of Nuclear anti-tumor effect of 4SC-202 was evaluated. Dose escalation part is completed Medicine, Royal Free Hospital, London, United Kingdom and data allow for reliable evaluation. Further patients will be enrolled to establish the MTD at prior dose levels. Background: Functional imaging using FDG-PET is increasingly used to Results: 24 patients were treated at 7 dose levels of 25/50/100/200/400mg QD assess the response to therapy of FDG-avid lymphomas. Clinicians generally and 200mg BID (N=3, each), and 200mg BID continuous dosing (N=6). refer to scans as either ‘positive’ or ‘negative’ however nuclear medicine Treatment was very well tolerated by heavily pre-treated patients up to the physicians recognise a continuum of uptake, with persistent disease more likely highest dose group. Possibly drug-related AE were less frequent, e.g. low- at higher levels of activity. Importantly, the glucose analogue used in this grade GI complaints such as nausea. Higher-grade hematological toxicity e.g. technique is not specific for lymphoma. Recently published studies that used a leading to treatment changes was not observed. Elevation of liver enzymes was program of biopsy or serial scanning and patient follow-up suggest poor positive observed at 200mg BID during continuous dosing. Two objective responses (PR predictive value of FDG-PET scans in some lymphoma subtypes. & CR, unconfirmed) were observed. 75% of patients went into follow-up Aims: We have analysed the clinical outcome of patients with initially FDG-avid treatment due to stable disease. Median time on treatment was 98 days with 3 lymphomas treated with curative intent who following completion of treatment patients treated > 400 days . Plasma exposure reached one digit µM had positive yet indeterminate findings at multi-disciplinary team (MDT) concentrations over 24h. Modulation of Wnt pathway gene-signature was meetings in two London teaching hospitals. Our aim was to determine how observed in blood samples, as well as HDAC inhibition and lysine acetylation. patients with such findings are managed and to determine the clinical outcome Summary and Conclusions: 4SC-202 could be safely administered up to for this cohort of patients. 200mg BID. Anti-cancer activity could be demonstrated by two patients Methods: We retrospectively reviewed all FDG-PET-CT end-of-treatment scan achieving PR and CR, respectively, and long term stabilization of several reports of patients with curable lymphoma subtypes over a seven year period. patients. The mode of action of 4SC-202 is demonstrated by biomarker Cases were selected if the scan reported persistent low grade uptake of response.

haematologica | 2014; 99(s1) | 713 19 th Congress of the European Hematology Association

PB1859 MANAGEMENT OF RELAPSED/REFRACTORY LYMPHOMA WITH BRENTUXIMAB VEDOTIN : OUR EXPERIENCE IN THE TREATMENT OF YOUNG PATIENTS C Cerchione 1,* C Cimmino 1, N Pugliese 1, E Seneca 1, R Della Pepa 1, S Luponio 1, C Mainolfi 2, F Pane 1, A De Renzo 1 1Hematology, 2Radiology, AOU “Federico II”, Napoli, Italy Background: Brentuximab vedotin is a CD30-directed antibody-drug conjugate (ADC), currently approved for treatment of relapsed Hodgkin lymphoma and relapsed anaplastic large-cell lymphoma after front-line chemotherapy. Aims: In this work, we analyze a successful experience with brentuximab vedotin in the management of relapsed and refractory lymphoma. Methods: Case 1 : N.A., 21 y.o. male patient, with diagnosis in November 2011 of Systemic anaplastic large-cell lymphoma (ALCL), Stage IIIB, non B non T, ALK-positive, CD30+. In November 2011 he underwent to frontline treatment CHOP/14 x 6 with CR. Then, he underwent to IEV protocol, but, after 2 courses, the patient referred to our Institution for abdominal pain : a PET/CT was performed documenting a relapse. So, he switched to DHAP, with an apparent improvement, but, one month after the first course there was a worsening of clinical conditions. Then, for progressive disease, there was a switch to Brentuximab treatment. After first course, the patient went to Emergency Medicine for respiratory problems, and, after the solution, we continued the protocol. The treatment was well tolerated, and, after 6 courses, the patient is in CR and he undergoes, in November 2013, to Allogenic BMT. Now, after 4 months, the patient has no signs of disease. Case 2 : T.A., 35 y.o. female patient, with diagnosis in February 2011 of classic nodular sclerosis Hodgkin’s Lymphoma, Stage IIB, with mediastinal bulky disease. Frontline treatment was ABVD, 12 courses, with the result of a PR. After, Radiotherapy was started on mediastinal mass, remaining in SD. After 3 months, there were new localizations documented from PET/CT and IGEV protocol was started, total of 3 courses, after which she underwent to AutoBMT in September 2012. PET/CT performed in February 2013 documented a progressive disease : Brentuximab was started and even if after 3 courses the patient was in SD, after 6 courses there was a PR, which became CR after 12 courses. The treatment was well tolerated, and the only documented side effect was alopecia. Case 3 : G.R., a female 30 y.o., with diagnosis in April 2004 of classic nodular sclerosis Hodgkin’s Lymphoma, Stage IIB, with splenic localization. Frontline treatment was VEBEP, 11 courses, with the result of a PR. Then, Radiotherapy was started but a relapse of disease was documented in May 2005. Then, programming a AutoBMT procedure, IGEV treatment was started, 3 courses and then she underwent to AutoBMT with a CR. In September 2006 PET/CT documented the second relapse : MOPP protocol was started (12 courses), until April 2007, when a PR was documented. In October 2007 a third relapse of disease was documented, treated with Gemcitabine, with a SD. The patient underwent to DHAP-R treatment, 4 courses, with the result of a PR. So, in October 2009, the patient started Rituximab maintenance, until July 2012, when it was interrupted for progression of disaese. In that moment the general condition were bad and the patient was not anymore able to walk. In that moment she switched to Brentuximab treatment and after 3 courses there was a nCR and after 6 courses she was in CR. The only side effect was a Grade 1 Neuropathy, which was documented only in the first three courses. Results: Brentuximab Vedotin has been proved to be effective either in relapsed/refractory Hodgkin’s and Non-Hodgkin’s Lymphoma as single agent, at the dose of 1.8 mg/kg. Summary and Conclusions: In our experience, Brentuximab Vedotin can be considered an effective option for advanced patients, relapsed and refractory to almost all available therapeutic resources, and moreover it could be considered as a bridge-treatment to AlloBMT.

714 | haematologica | 2014; 99(s1)