in Group I, and bone pain (36.8% grade I, 18.4% grade 2, 2.6% P408 grade III), headache (2.6%), nausea (10.5%), and a mild splenomegaly (5.3%) in group II, respectively. No donor Reduced-intensity conditioning followed by allogeneic developed long-term adverse effects in both groups. The CD34 transplantation has a better outcome than high-dose (+) cell count in the first aphaeresis was 4.9 x 10(6)/kg donor chemotherapy plus autografting in T-cell non-Hodgkin's weight (range, 1.3-22.3) in the group I and 6.0 (1.3-17.3) in the group II (p = n.s.). The target of collecting >5.0 x 10(6) CD34 (+) P. Corradini, A. Dodero, F. Zallio, M. Dinicola, D. Caracciolo, F. cells/kg donor weight with one aphaeresis procedure was Ciceri, A. Cuttica, M. Boccadoro, A. Gianni, A. Pileri, C. Tarella achieved in 43.7% of group I and in 44.71% of group II. Target (Milan, Turin, I) CD34+ cells was reached in all cases with a median number of 9.4 (range 6-17,4) and 10 (range 0-20) CD34+ x 10(6)/kg donor Non-Hodgkin with T-cell histology (T-NHL) usually weight collected, respectively, with no statistical difference. A have an aggressive clinical course with a dismal prognosis. To median of 2 procedures (range 1-4) was performed in both address the role of transplantation procedures in T-NHL, we groups for single donor. PBPC collection was associated with a have conducted a retrospective analysis on 29 patients: 15 PTCL decrease in platelet count, which was not significantly different unspecified, 11 AILD, one angiocentric, one ALCL CD30+, and between two groups. After the last PBPC collection, platelet one CTCL panniculitis-like. Patients were treated with high-dose counts were within normal limits 5.5 + 3.4 and 8.7 + 6.1 days, sequential chemotherapy (HDS) followed by autografting (group respectively (p= 0.016) while WBC returning to baseline values A=20) or nonmyeloablative allogeneic transplantation (group at mean day 9.4 + 8 in group I, and 9.5 + 7 in group II. B=9). Seventeen patients were treated at diagnosis and 12 at In conclusion lenogastrim and filgastrim mobilization of PBPC relapse. All patients at diagnosis had a 2 or 3 IPI score. The were similarly in terms of collection and short-term and long-term median age was 46 yrs (range: 20-64). Twenty patients received adverse effects in normal donors. HDS chemotherapy but only 13 attaining PR or CR underwent the final autografting phase. HDS chemotherapy consisted of: 2 APO and 2 DHAP courses, etoposide 2 g/ms, methotrexate Physicians Poster Session: Lymphoma 8g/ms, and cyclophosphamide 7g/ms. Autotransplant conditioning regimen consisted of novantrone (60 mg/ms) and melphalan (180 mg/ms) in 10 patients and other conditioning P407 regimens in 3 (n=1 BEAM, n=1 TBI/Alkeran, n=1 BCNU/VP- Prognosis of patients with aggressive peripheral T-NHL 16/Thiotepa). Nine patients were allografted after disease does not differ from patients with diffuse large B-cell recurrence, and 4 of them already failed a previous lymphoma when high-dose therapy and autologous stem autotransplant. Before allografting they received 4 DHAP cell transplantation are applied courses. Conditioning regimen consisted of thiotepa (10 mg/kg), fludarabine (60mg/ms) and cyclophosphamide (60mg/kg). In a P. Jindra, V. Koza, K. Cerna, M. Karas, D. Lysak, P. Skopek, M. group A, all patients received peripheral blood stem cells, Svojgrova, V. Vozobulova, M. Schutzova (Pilsen, CZ) whereas in a group B, 2 patients received marrow cells and 7 Patients (pts) with peripheral T-cell lymphomas (PTCL) except peripheral blood stem cells. All patients engrafted; there was one for ALCL were shown to have a poor prognosis with conventional treatment-related death in group A. The median follow-up from chemotherapy (Blood, ILSG, 89:3909, 1997), however, the role the date of inclusion in the program was different in the two of High-Dose Therapy (HDT) and Autologous Stem Cell groups: 50 months (group A) and 24 months (group B). Using an Transplantation (ASCT) in this setting remains unclear. We thus intention-to-treat analysis, the estimated probability of PFS and retrospectively analysed 25 consecutive pts with PTCL OS at 24 months in group A were 38% and 40% respectively. (excluding ALCL) undergoing ASCT and compared their For group B, the estimated probability of PFS and OS at 20 outcome with the control group of identically treated pts with months were 76% and 87% respectively. Our findings, although Diffuse Large B-Cell Lymphoma (DLBCL). on a limited number of patients, suggest the following Since 1994 all patients with newly diagnosed or relapsed PTCL conclusions: 1) high dose chemotherapy and autografting are not in our dpt. have been treated with anthracycline-based regimens curative in the majority of T-NHL; 2) allografting is an effective followed by HDT (BEAM)+ASCT. Their median age was 47 years salvage treatment; 3) the existence of durable CRs after a failed (range 18-72); 22 pts had large cell PTCL unspecified, 2 pts autograft is an indirect evidence of the graft versus T-NHL effect. lymphoepiteloid and 1 pt angioimmunoblastic (AILD) subtype. 4 It has to be pointed out that 6 of 9 patients in remission after pts (16%) were beyond 1.CR/PR, 1 pt (4%) showed primary allografting developed chronic GVHD. progressive disease whereas remaining 20 pts (80%) received HDT as a 1st line treatment when in 1st CR/PR. According to IPI, P409 12 pts (48%) were in the low/low-intermediate risk group, 13 pts (52%) in the high-intermediate/high risk group at dg. or at Tandem high-dose therapy including treosulfan, melphalan relapse. At median follow-up of 38 (17-83) months, 20 pts (80%) and thiotepa with autologous stem cell transplantation for are alive and 4 pts (%) have relapsed or progressed (1,2,6 and relapsed or refractory high-grade lymphoma 37 mts postASCT). 3 of the relapsed died, 2 pts died of M. Koenigsmann, M. Mohren, A. Franke, E. Becker, M. Heim, C. secondary malignancy in CR. The estimated probabilities of 5- Kahl, M. Freund, J. Caspar (Magdeburg, Rostock, D) year EFS and OS are 64% and 70%. The control group of 30 DLBCL pts treated at the same period does not differ for any Introduction: To improve the prognosis of relapsed and refractory clinically significant variables such as age (p=1.0), stage at dg. high-grade lymphoma patients the East German Study Group (p=0.27), IPI distribution (p=1.0), status of disease at ASCT (p= Hematology and (OSHO) started a phase I/II trial 1,0). Also mobilizing as well as conditioning regimens were the chosing a new tandem high-dose approach. same for both groups of lymphoma patients. With median follow- Treatment plan: For cytoreduction and stem cell mobilisation, 1 up of 51 (16-90) months for DLBCL pts we observed no apparent cycle of DexaBEAM and 1 cycle of etoposide at 2g/m2 are difference in 5-years EFS (77% for DLBCL vs. 64% for PTCL; applied. The first high dose therapy (HDT) includes treosulfan p=0.91) and OS (83% for DLBCL vs. 70% for PTCL; p=0.74). with melphalan at 140 mg/m2 total dose, the second HDT Conclusion: Our data suggest that prognosis of PTCL pts except treosulfan with thiotepa at 250 mg/m2, both followed by for ALCL does not differ from DLBCL when HDT with ASCT is autologous peripheral stem cell transplantation. Treosulfan exploited. However, the exact place (e.g. timing) of HDT+ASCT dosage is studied at 30, 39, and 48 g/m2 total dose per high- in the management of PTCL needs to be determined. dose cycle. Results: So far, 17 pts (25-61yrs, stages II: 4, III:6, IV: 7pts) have

S67 been enrolled, 10 with relapsed and 7 with primary refractory discriminate residual/relapsed disease from reactive disease. Histology included diffuse and anaplastic large cell proliferation; (iv) the significance of R-induced, T-LGL mediated lymphoma, grade II-III (1 pt), Hodgkins and cytopenias in alloHCT (reported here for the first time) needs pleomorphic T-cell lymphoma. Seventeen pts received further evaluation. DexaBEAM, 11 of these etoposide, 10 pts received 1st HDT, and 5 pts completed 1st and 2nd HDT, all with 30g/m2 treosulfan. P411 Individual peak values of CD34+ cells per ml peripheral blood after mobilisation ranged from 20 to 1,720 (median 141) x10e3 Failure of primary autologous stem cell transplantation to after DexaBEAM (n=9) and from 15 to 704 (median 68) x10e3 cure Waldenström's macroglobulinemia after etoposide (n=6). Accordingly, 1 to 2 stem cell collections B. Seyfarth, R. Sonnen, M. Zeis, C. Renk, R. Schoch, N. were sufficient for tandem transplantation. CTC °III and °IV non- Schmitz, P. Dreger (Hamburg, Kiel, D) hematological toxicities besides alopecia: 6/10 pts after 1st HDT had °III toxicities (infection, vomiting, stomatitis) and 1 pt °IV Waldenström’s macroglobulinemia (WM) is an incurable toxicity (stomatitis). 2/5 pts after 2nd HDT showed °III toxicities lymphoproliferative disorder. Since conventional chemotherapy (infection, stomatitis, vomiting, diarrhea, liver enzyme elevation) with alkylating agents or purine analoga can only achieve and 1pt °IV toxicity (stomatitis). Median hematological recovery temporary remissions, the prognosis of WM is dubious with a (>1.0 leuko/nl and >20 plt/nl) after 1st and 2nd HDT was median overall survival of about 5 years. The purpose of this achieved by d 9 (8-9) and 11 (8-14), and d 9 (7-11) and 12 (9-14) study was to investigate the role of autologous stem cell respectively. No toxic death occurred. 7/16 evaluable pts entered transplantation (SCT) for the treatment of WM. Ten patients (age CR: 1 after DexaBEAM, 1 after etoposide, but 5 pts only after the 39-58 years) with WM were treated with 1-3 cycles of Dexa- 1st (n=4) or 2nd HDT (n=1). At 11 to 18 months after therapy, BEAM chemotherapy + G-CSF for stem cell mobilization followed four pts are in continuous CR. Two pts progressed after CR, one by myeloablative therapy with total body irradiation / high-dose with previously refractory disease, one with follicular lymphoma cyclophosphamide and PBSCT. In the first 5 patients, grafts grade II-III. Seven pts died, 6 due to disease progression, 1 pt were vigorously B-cell-depleted by immunomagnetic CD34+ due to secondary AML. Five of these pts died before HDT. and/or negative B cell selection. Four patients were untreated, Conclusions: Tandem HDT was feasable and effective. four were in first remission, and two had more advanced disease. Maximum tolerable toxicity of treosulfan within this protocol has Prior to treatment, serum IgM levels were 24.1 (11-67.7) g/L, and not yet been reached and the dosage escalation study will all patients had symptomatic disease due to anemia, lymphoma, continue. hyperviscosity, or . Results: 5 (2.1-13.2) x106/kg CD34+ cells were reinfused after P410 myeloablative therapy. En-graftment was prompt, however, one patient died due to refractory autoimmune thrombopenia 6 T-large granular lymphocyte mediated cytopenias in months post transplant. Although SCT resulted in a strong Rituximab -treated lymphoma patients undergoing reduction or normalisation of serum IgM levels in all patients (4.6 hematopoietic cell transplantation (2.1-23.2) g/L at 100 days post transplant) immunofixation K. Stamatopoulos, I. Sakellari, P. Kaloyiannidis, T. Papadaki, A. remained monoclonal in all but 2 patients, suggesting Tsompanakou, A. Asimaki, A. Anagnostopoulos, A. Fassas persistence of residual disease. With a median follow-up of four (Thessaloniki, Athens, GR) years, disease progression was observed in 7 of 9 patients at risk, translating into a median progression-free survival of 39 Transient neutropenia has been reported post auto- months. Nevertheless, the 4-year estimates of treatment-free hematopoietic cell transplantation (HCT) in lymphoma patients survival (71% (95%CI 36-100)) and overall survival (89% (95%CI who received Rituximab (R) either for in vivo purging or as 68-100)) suggest a significant therapeutic benefit of SCT in WM. adjuvant therapy. No explanation has been given for this effect. Conclusions: This pilot trial shows that high-dose We describe eight lymphoma patients who received R and radiochemotherapy with B cell depleted autografts is effective developed profound and prolonged (1-5 months duration) and may improve the course of patients with WM. Complete neutropenia and/or thrombocytopenia post-HCT. Four patients eradication of the disease, however, definitely requires additional [2, diffuse large cell lymphoma (DLCL)/ 2, interventions. The peritransplant in-vivo use of monoclonal (MCL)] underwent matched related alloHCT (2/4 RIC) and four antibodies might be a candidate approach for this goal. (DLCL: 3, MCL: 1) autoHCT. Patients received a median of 4.3 x 106 CD34+ cells/kg (range, 3.0-7.1). Cytopenias developed a P412 median of 75 days post-HCT (range 40-135), after prompt and timely engraftment; at onset of cytopenias, only 1/4 allo- High-dose sequential followed by autologous bone marrow transplanted patients had evidence of chronic GVHD (135 days transplantation is effective and safe salvage treatment in post-HCT). All patients were negative for hepatitis B surface advanced Hodgkin's disease antigen and HIV, CMV, EBV and antibodies. M.T. Delamain, R.B. Cardoso, K.B.B. Pagnano, G.B. Oliveira, Morphological, and immunophenotypical analyses of peripheral A.C. Vigorito, F.J.P. Aranha, K.A.B. Eid, E.C.M. Miranda, C.A. blood (PB) and bone marrow (BM) revealed: (i) proliferation of De Souza (Campinas, Marilia, BR) cells with typical T-large granular lymphocyte (T-LGL) profile (CD3+CD8+CD57+CD28-, CD8+ >/= CD4+ cells) (i) mild to Autologous bone marrow transplantation (ABMT) has been moderate BM infiltration by small lymphocytes, exclusively of T proposed as a salvage treatment of resistant / refractory origin with T-LGL phenotype; (ii) mild to moderate depression of Hodgkin's disease (HD). High dose sequential (HDS) using the myeloid series with a left shift. At a median follow-up of 13 cyclophosphamide 7g/m2 for debulking and PBPC mobilization months (1-23), only one patient (allo-tranplanted DLCL) followed by MTX 8g/m2 and then VP-16 2g/m2 before ABMT, developed a severe infection (interstitial pneumonia) of which he described by Milan group, seems to be effective for this category died; otherwise, infection incidence was not increased. of patients. Furthermore, neutrophil count promptly increased with G-CSF Objetive: We report the results obtained in 31 patients with administration. In conclusion: (i) cytopenias and/or T-LGL PB Hodgkin's disease who failed conventional therapy or relapsed might be one end of the spectrum of within 24 months of therapy. immunohematological sequellae of R-mediated T-LGL Methods: Patients were treated with HDS followed by ABMT expansion; (ii) R-mediated T-LGL expansion should be receiving BEAM (BCNU, Etoposide, Ara-C and Melphalan) as considered in the differential diagnosis of cytopenias post-HCT; conditioning regimen. The median age was 25 years (12-61), 20 (iii) thorough follow-up of R-treated patients is mandatory to male (64,5%) and 11 female (35,5%). The histology at diagnosis

S68 showed: 19 (61,3%) nodular sclerosis; 9 (29%) mixed cellularity; P414 2 (6,5%) lymphocyte-depleted and 1 (3,2%) lymphocyte-rich HD. Bulky disease was presented in 15/30 (50%) patients and 6/30 Autologous stem cell transplantation for follicular (20%) had bone marrow infiltration. lymphoma: a nation-wide analysis from Finland Results: The Overall survival (OS) and disease free survival E. Jantunen, E. Juvonen, S. Leppä, O. Kuittinen, T. Lehtinen, M. (DFS) were 49% (n=31) and 60% (n=15), respectively, in 1825 Itälä, E. Elonen, T. Nousiainen (Kuopio, Helsinki, Oulu, Tampere, days. The OS was 62% for patients with 0-1 prognostic factors at Turku, FIN) diagnosis and a shorter OS was observed in patients with more than 2 prognostic factors (P=0.004). Bulky disease , histology Autologous stem cell transplantation (ASCT) for follicular type and bone marrow involvement did not correlate with lymphoma (FL) has been studied mostly in single centre series. prognosis. Forteen patients died, 6 due to progressive disease We have performed a retrospective nation-wide analysis on the (42,9%), 6 due to infection (43,8%) and one (7,1%) due to feasibility and efficacy of ASCT in patients with FL in Finland. hematological toxicity after ABMT. Status presens for alive Altogether 85 patients received ASCT in six transplant centres patients after a median time of 783 days (range 50-1929) from between January 1994 and August 2002. There were 38 males transplant is: CR 11 (35,5%), partial response 2 (6,5%) and 4 in and 47 females with a median age of 48 yrs (26-65). The median progressive disease (12,9%). time from the diagnosis to ASCT was 16 months. Twenty-eight Conclusion: We conclude that HDS followed by ABMT is an patients (33%) had a transformed disease before ASCT. Disease effective salvage regimen for patients with resistant/refractory status at ASCT was Ist CR/PR in 48% of patients. High-dose Hodgkin's disease and probably induces a long and stable CR therapy consisted mostly from BEAC (N=54) or BEAM (N=25) mainly in chemosensitive patients. Patients presenting >2 and was supported by blood stem cells in 93% of the patients. prognostic factors at diagnosis presented worst outcome. This is The early transplant-related mortality (TRM) was 3.5%. One the first experience in Brazil using this procedure in HD. patient developed secondary acute leukaemia. Until now, 25 patients (30%) have relapsed with a median time of 11 months from ASCT. Overall survival (OS) and progression-free survival P413 (PFS) were 79% and 55% at 5 years, respectively. Patients Pre- and postmobilization factors affecting progenitor cell transplanted in Ist CR/PR had superior PFS when compared to mobilization with intermediate-dose cyclophosphamide and the patients transplanted later (72% vs. 40% at 5 yrs, p<0.0088). granulocyte-colony-stimulating factor in non-Hodgkin's Patients transplanted after a transformation had equal lymphoma patients progression free survival when compared to others. To conclude, ASCT is feasible in patients with FL with a low TRM and low T. Kuittinen, T. Nousiainen, E. Mahlamäki, E. Jantunen (Kuopio, incidence of secondary leukaemia. Randomised studies are FIN) needed to assess more clearly the role of ASCT in addition to Background: Blood progenitor cells are increasingly used instead other current treatment options in patients with FL. of bone marrow to support high-dose therapy in lymphoma patients. Factors affecting progenitor cell mobilization are P415 currently incompletely understood. Patients and Methods: We analysed retrospectively factors Long-term follow-up of autologous stem cell transplant in potentially affecting progenitor cell mobilization in 97 consecutive HIV-1+ high-risk lymphoma patients patients with non-Hodgkin's lymphoma (NHL) who received D. Serrano, R. Carrion, P. Balsalobre, P. Miralles, J. Berenguer, mobilization with intermediate-dose cyclophosphamide (CY) S. Resino, M.A. Munoz-Fernandez, A. Gomez-Pineda, I. Buno, (4g/m2) followed by granulocyte-colony-stimulating factor (G- J.M. Ribera, J.L. Diez-Martin (Madrid, Badalona, E) CSF) (5 ug/kg/d) in 1995-2000.There were 59 males and 38 females with a median age of 49 years (16-70). Introduction: High Activity Antiretroviral Therapy (HAART) has Histology: large cell B 50 pts, mantle cell 16 pts, follicular 16 pts, improved the outcome of patients (Pt) diagnosed of AIDS-related others 15. Initially bone marrow infiltration was observed in 37 lymphoma (ARL). This treatment has allowed for an increase in pts (38%). Disease status at the time of mobilization: the intensity of treatment used in ARL that is becoming similar to ICR/PR/refractory 66 pts, other 31pts. The criterion for that used in lymphoma-HIV negative. successful mobilisation was collection of >1.0x106/kg CD34+ Patients and Methods: 10 Pt with AIDS (stage C3) and high-risk cells. Lymphoma uderwent mobilization and collection of Results: Eighteen patients (19%) failed to achieve this minimum hematopoietic stem cells (HSC). We used high doses of G- threshold. In univariate analysis premobilisation factors CSF(20mcg/kg/d) as mobilization protocol in 7 Pt, plus CTX 1,5 associated with mobilization failure included BM involvement at grs/m2 x 1 day in 3. HSC were programmed criopreserved and diagnosis (p=0.004), BM involvement prior to mobilization stored in isolated chamber at –80ºC. (p=0.013), previous use of fludarabine (p=0.014) and lower Three mobilized Pt died before autologous stem cell transplant platelet count prior to mobilization (p=0.001). Postmobilization (ASCT) (1Pt VHC disease and 2 Pt ARL progression). ASCT factors associated with unsuccessful mobilization included lower was performed in 7 Pt (4 NHL and 3 HD). ASCT indications leukocyte nadir (p<0.001), lower platelet nadir (p<0.001), were: ARL relapse (2 Pt), high risk histology at diagnoses neutropenic fewer (p=0.001), later peak B-CD34+counts (Burkitt-Lymphoma, 2 Pt) or not achieving a complete remission (p<0.001), lower peak B-CD34+ counts after mobilization (CR) after the 1st line of treatment (3 Pt). Disease status at (p<0.001) and higher need for platelet transfusions (p<0.001). In conditioning was CR for 6 Pt and PR for 1 Pt. Conditioning multivariate analysis only BM involvement at diagnosis (p=0.004) regimen used was BEAM. HAART was maintained during and platelet count prior to mobilization (p=0.009) were mobilization and ASCT, except during conditioning in Pt 136, associated with an unsatisfactory mobilization. These two which was necessary to resume due to an increase in HIV load. parameters were then used to build a mathematical model G-CSF was used in all Pt from day +7 until engraftment. predicting the probability of each patient experiencing a Results: Median of collected CD34+ cells was 4,25x106/kg (1,8- mobilization failure. The area under the ROC curve, which is a 16). Median time to reach PMN>0.5x109/L was 18 days (13-33) clinical performance of the model, was 83%. and 20 days (17-36) for platelets>20x109/L. 2 Pt did not reach Conclusions: Several pre- and postmobilization factors affecting platelet >20x109/L (UPN 160, JGG). Toxicity and infectious progenitor cell mobilization were identified in this study. Of events: 7/7 Pt had neutropenic fever (1 Pneumonia, 3 premobilization factors BM infiltration at diagnosis and platelet bacteriemias and 3 fever of unknown origin). 1 Pt had herpes count prior to mobilization turned out to be useful parameters zoster 1 year after ASCT. Grade II mucositis occurred in 4 of 7, predicting who will be ‘hard to mobilize’. grade II hepatic toxicity occurred in 1 of 7 Pt. Pt JGG died 20

S69 days after transplant due to ARL progression. Other 6 Pt are P417 alive and in CR. The median follow-up is 18 months (2-29). Conclusions: HSC obtained from our patients showed an Rituximab plus chemotherapy, CD34+ cell aelection and adequate number of CD34+ cells for ASCT. Mobilization and high-dose chemotherapy in advanced stage mantle-cell conditioning programmes did not increase the viral load (VL), as lymphoma long as HAART was maintained. ASCT was not associated with G. Martinelli, A. Alietti, S. Cinieri, C. Rabascio, C. Corsini, A. an increased conditioning related toxicity and opportunistic Agazzi, K. De Luzio, E. Cocorocchio, P.F. Ferrucci, D. Laszlo, F. infections. ASCT may be applied with guarantees to treat Bertolini (Milan, I) patients diagnosed of AIDS-related lymphoma. Mantle-cell lymphoma (MCL) is a CD20+ lymphoproliferative disorder, currently incurable with standard therapy. The role of different treatment modality is still under investigation. Preliminary results about the combination of HD CT and monoclonal antibody seem to suggest a possible improvement in terms of EFS, principally among patients (pts) who obtained a clinical and molecular (bcl-1) complete remission after first line therapy. Here we consider the feasibility of a program therapy involving rituximab plus CT, CD34+ positive selection and HD CT in pts with advanced and refractory MCL. We treated so far 11 pts, (7 newly-diagnosed, 4 previously-treated), median age 55 y (45-62), 10/11 in stage IV. All pts had bcl-1-positive marrow, 2

had bulky disease, 3 had leukemic picture and IPI was >2 in 7/11. Pts received rituximab (375 mg/m2) at the first day of each P416 treatment consisting of 2 CHOP-like cycles, CTX 4 g/m2 and G- High dose chemotherapy and stem cell transplantation for CSF to collect >2x10^6 CD34+cells/Kg (apheresis were advanced or refractory childhood Hodgkin’s Disease processed by CliniMACS for CD34+ cell purification), 2 HD- ESHAP and CD34+ cell reinfusion after IDA 15 mg/m2 and L- A. Pession, F. Locatelli, A. Prete, C. Favre, R. Rondelli, C. PAM 180 mg/m2. 10/11 pts are fully evaluable. Before HD CT, 5 Messina, G. Dini, C. Uderzo, R. Burnelli on behalf of the AIEOP- pts achieved CR and 5 were in PR. After the combined rituximab BMT Group plus in vivo purging CT, 9/10 pts had bcl-1-negative CD34+ cell Objectives: We analysed the results of stem cell transplantation collections, including one patient who had a bcl-1-positive (SCT) performed in a exclusively paediatric setting of pts apheresis which became bcl-1-negative after CD34+ cell affected by Hodgkin’s Disease (HD) and reported to BMT selection. In one pt the CD34+ cell collection remained bcl-1- Registry of AIEOP (Italian Pediatric Hematology-Oncology positive. Seven out of ten pts are in CR (confirmed by PCR), one Association). pt, who failed to collect bcl-1-negative CD34+ cells, relapsed 6 Methods: Between 1/86 and 12/01, 66 SCT were performed in months after CR, an other one relapsed at 28th month after 61 pts with HD, 36 M/25 F, median age 15 (6-17) yrs. 59/66 were achieving clinical and molecular CR and the last one has been autoSCT (3 double) and 7 were alloSCT (1 double). 29 SCT not evaluated for response yet. Infective complications were: 5 were performed in second or subsequent CR and 37 in more FUO, 1 pneumonia, 2 CVC infections, 2 CVC thrombosis. Three advanced phase of disease. First line therapy was a pts experienced G1 thrombocytopenia 3 months after conventional treatment, consisting of MOPP/ABVD and involved transplantation, persisting in one patient until 12 months after field radiotherapy for the majority of pts. Most of HDCT regimens transplant. Despite the low number of the patients considered in consisted of chemotherapy, while TBI was administered in only 2 this preliminary experience, our data suggest that rituximab plus cases. The source of SC was autoBM in 36 cases, autoPBPC in CT in combination with CD34+ cell purification and sequential 26 and both in 4. A median number of 2.15 x 108/kg MNC (range HD CT is associated with an high molecular remissions rate in 0.48-21.62) and 5.70 x 106/kg CD34+ cells (range 0.58-45.53) advanced or refractory MCL pts. The relevance of these were infused. preliminary results need further confirmation and comparisons Results: All patients achieved ANC and PLT engraftment between molecular and clinical outcome. respectively after a median time of 13 (8-54) and 23 (10-163) days. After a median FUP of 32 (1-161) mos, the 5 yrs OS (IC P418 95%) of the pts grafted with autoSCT was 64.4% (69-79), while 5 and 10 years EFS (IC 95%) were 58.2% (44-72) and 43.7% (23- Autologous stem cell transplantation as consolidation 64) respectively. 23/56 pts relapsed after a median time of 9 (2- treatment in aggressive non-Hodgkin’s lymphoma patients 46) mos. II CR and HDCT containing BCNU can offer a better in remission after conventional chemotherapy EFS (76.7% e 71.8% respectively). 4/6 pts that received an A Sperotto, F. Zaja, F. Patriarca, F. Silvestri, M. Tiribelli, A. alloSCT are alive and well after a median FUP of 15 (2-107) Geromin, A. Candoni, R. Stocchi, D. Damiani, C. Filì, E. Calistri, mos. Transplant related toxicity was moderate and 100 days R. Fanin (Udine, I) TRM was 3,7%. Discussion: SCT is actually to be regarded as a choice option in Background and Objectives. To analyse the outcome of 121 patients with refractory disease and in those with early relapse aggressive non-Hodgkin’s lymphoma patients submitted to (first remission <1 year) only, pts showing these characteristics autologous stem cell transplantation in remission after and who undergo autoSCT have a significant better outcome conventional chemotherapy. compared with those receiving any alternative conventional Design and Methods. Patients were considered as having an treatment. The late relapse and the good outcome of alloSCT high risk disease and then included in the program if they described in our little subset of pts, could represent indications to present at least one of these features at diagnosis: stage III-IV; B test alloSCT in a well defined subgroup of bad risk patients. symptoms; bulky disease. Median age at diagnosis was 42 (15 – 60) years; male/female ratio – 1.6. They were affected by diffuse large B cell lymphoma – 61 (50.0%); anaplastic large cell lymphoma T or null cell type – 21 (17.5%); T precursor lymphoma – 9 (7.5%); follicular lymphoma – 16 (13.0%); peripheral T cell lymphoma unspecified – 6 (5.0%); marginal zone lymphoma – 4 (3.5%); mantle cell lymphoma – 4 (3.5%).

S70 Eighty-four out of 121 (69.5%) patients were in stage III-IV, 59 effects were negligible and no patient was admitted to the (48.5%) had a bulky disease and 60 (49.5%) had B symptoms. hospital to manage toxic effects. Distribution according to the I.P.I. was: low (L+LI) - 81 (67.0%) Twenty-nine pts are evaluable after PBSCT, which converted PR patients; high (HI + H) – 40 (33.0%) patients. First line treatment in CR in five cases. After a median follow-up of 19 months (range were in according to the third generation regimen (F-MACHOP 4-46), 17 of these pts are alive and disease-free, one is alive and for 6 cycles). disease-free after salvage RT, two are alive with disease, and Status at transplant was: complete remission – 74 (61.5%) nine are died (7 for HD, 2 in CR from causes probably related to patients; partial remission - 47 (39.0%) patients. transplant procedure in one case). Actuarial two-year freedom ASCT was performed using BAVC as conditioning regimen. from progression and overall survival are 67% and 74%, Results. As by October 2002, with a median follow-up from respectively. transplant of 50 months (3 – 143), 89.0% (108 out of 121) of the Conclusions : IGEV is a very effective cytoriductive and patients were in CR, 5 (4.5%) were alive with disease and 8 mobilizing regimen with acceptable toxicity in patients with (6.5%) died (2 for transplant related complications). resistant/relapsed Hodgkin’s disease. After ASCT, the rate of complete remission increased from 61.0% to 89.0%, with a conversion of the response of about P420 72.5%. OS and PFS of the whole population are respectively 90.0% and High-dose therapy and autologous peripheral blood stem 87.0% with a median follow-up from transplant of 50 months (3 – cell transplantation for HIV-associated lymphoma 143. A. Re, C. Cattaneo, S. Casari, M. Spina, M. Michieli, M. Rupolo, OS according to status at transplant was: CR patients - 93.5%; A. Nosari, P. Ferremi, A. Lanfranchi, M. Mazzuccato, L. PR patients – 83.5% (p value <.02).A statistically significant Abruzzese, U. Tirelli, G. Carosi, G. Rossi (Brescia, Aviano, difference clearly emerges considering PFS according to status Milan, I) at transplant: CR patients – 93.5%; PR patients – 76.5% (p value= <.01). The introduction of highly active antiretroviral therapy (HAART), Conclusions. From our results, that seems to be in excess of by restoring the immune system defect in HIV-positive pts, has what would be expected in a group of patients with the same allowed the use of aggressive treatment in HIV-associated characteristics treated with standard chemotherapy only, to be at lymphoma (HIV-Ly). We started a program of High-dose therapy least in partial response at transplant seems to be enough for (HDT) and PBSC transplant as salvage therapy for pts with predicting a favourable outcome. Moreover, with a median refractory or relapsed HIV-Ly. Inclusion criteria comprised follow-up from transplant of 50 months, no secondary leukaemia availability of effective HAART, absence of active opportunistic and myelodisplastic syndrome has been already observed. infections (OI) or CNS lymphoma and sensitivity to 1/more courses of second-line standard-dose chemotherapy (CT). Up to P419 Nov 2002, 13 pts entered the program, 8 with HD (three 1st relapse, two 2nd relapse, three refractory) and 5 with NHL (three IGEV chemotherapy and consolidation with peripheral blood 1st relapse, one partial remission, one refractory). Median age stem cell transplantation for refractory-relapsed Hodgkin’s was 39 (31-56) and CD4 count 162/cmm (17-451); bone marrow disease was involved in 4 cases. Three pts had detectable HIV-viremia M. Balzarotti, M. Magagnoli, L. Castagna, M. Spina, L. and 7 had chronic HCV hepatitis. All pts had received intensive Siracusano, M. Michieli, A. Nozza, B. Sarina, I. Timofeeva, S. first-line CT. One pt with refractory HD died soon after second- Compasso, U. Tirelli, A. Santoro (Rozzano-Milan, Aviano, I) line treatment for disease progression. One pt is undergoing mobilizing treatment. In 9/11 pts an adequate number of CD34+ Purpose: High dose chemotherapy with peripheral blood stem cells was collected, after cyclophosphamide 4 gr/sqm + G-CSF in cell transplantation (PBSCT) is standard approach in eligible 3 and G-CSF-supported CT in 6 cases. A median of 6.3 (4.1 - patients (pts) with relapsed/refractory Hodgkin’s disease (HD). 8.3) x 106/Kg CD34+ cells were collected, after 2 (2-3) However, as disease status at transplant is a major prognostic apheresis. One pt had progressive HD after PBSC collection and factor, the question of which is the best induction regimen before died. One pt is too early and seven underwent HDT with BEAM PBSCT is still debated. In this setting, our objective was to (BCNU 300mg/mq, VP16 200mg/mq x 4, Ara-C 200mg/mq x 4, determine the efficacy and mobilizing potential of the IGEV Mel 140mg/mq) and PBSC transplant. Prompt hematologic regimen recovery was observed in all pts (PMN>500/cmm at +10 (8-10) Methods : IGEV consists in ifosfamide 2000 mg/mq IV d 1-4; and plts>20.000/cmm at +12 (8-18)). Treatment-related toxicities: gemcitabine 800 mg/mq IV d 1 & 4; vinorelbine 20 mg/mq IV d 1; three WHO 3 and one WHO 2 oral mucositis and one WHO 3 prednisolone 100 mg/mq IV d 1-4, and G-CSF 300microg sc d 7- hepatic toxicity. Infectious complications during neutropenia: one 12 or up to PBSC harvest. Treatment program consists in 4 facial cellulitis, one Staph. Epidermidis and one E. Coli sepsis IGEV cycles (cy) at 3-week interval as induction, followed in and one Clostridium colitis. HIV viral load remained undetectable responding pts by high dose chemoterapy (HD-CT) with thiotepa in all pts on HAART except one. OI were seen in 3 pts and (600 mg/mq d –3) and melphalan (140 mg/mq d –1) with PBSC responded promptly to treatment: varicella zooster at 5 mo and reinfusion on day 0 or tandem transplant with Melphalan (200 esophagus candidosis at 9 mo in 1 pt; varicella zooster at 3 mo mg/mq) and BEAM regimen. in a pt and esophagus candidosis at 9 mo in 1 pt. In 6/7 pts a CR Results : At present, fourty pts are evaluable after IGEV. M/F: was achieved and four are alive and disease-free 1, 5, 6 and 12 12/28; median age: 30 years (18-59); refractory/relapsed 11/29; mo after transplant. Relapse occurred in two pts at 5 and 12 mo. median prior regimens: 1 (1-2); prior radiotherapy (RT) 22; stage In conclusion, in HIV-Ly an aggressive treatment approach with III-IV disease or multiple extranodal sites involved at accrual 32. HDT and PBSC transplant seems feasible, with rapid Two pts previously treated by HD-CT and PBSCT received non- hematologic recovery and acceptable toxicity. The impact on HIV myeloablative allogeneic PBSCT from HLA identical siblings. infection seems mild in pts on HAART. Clinical results on IGEV induced 20 complete remission (CR) and 12 partial lymphoma are encouraging remission (PR) for an overall response rate of 80%, with two patients progressing while on treatment. Median number of CD34+ cells collected was 6.6 x106/Kg (range 0.9-23) after a median of two (range 1-3) apheretic procedures. Grade 3-4 neutropenia occurred in 34% of 154 cycles, grade 3-4 thrombocytopenia in 29% with four pts transfused, and grade 3-4 anemia in 25% with one pt transfused. Nonhematologic side

S71 P421 All patients received 3 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, 6-methilprednisolone) as debulking Salvage therapy with pegylated lyposomal doxorubicin and therapy. After this, they were twice mobilized for peripheral blood rituximab plus GM-CSF in heavily pretreated lymphoma stem cell (PBSC) collection, at first with cyclophosphamide 7 patients relapsing after transplantation gr/m2 (CTX)+ rituximab 375 mg/m2, followed by subcutaneous M. Lucesole, D. Capelli, M. Montanari, G. Gini, S. Cecchi, L. G-CSF 300 mg/die and subsequently with ARA-c 8gr/m2 + Spitaleri, A. Poloni, P. Leoni, A. Olivieri (Torrette di Ancona, I) rituximab and G-CSF. Overall, sufficient number of PBSC (>3 x 106 CD34+ cells/kg) was harvested in all patients. All the Patients with HG NHL, relapsed after transplantation, have a patients were conditioned with BEAM (BCNU, etoposide, very poor prognosis. We treated 11 patients, relapsed after aracytin, melphalan) and subsequently PBSC were infused. transplantation, affected by aggressive NHL with the association Transplant-related complications were one cerebral bleeding Pegylated Lyposomal Doxorubicin (PLD)-Rituximab. The median observed during cytopenia in one patient, septic fever in 5 age was 51 (28-76), 9 patients were affected by B large cells patients, grade II-III mucositis in 16 patients; in addition, three lymphoma, 2 by MCL. The median time of relapse after patients experienced HBV reactivation, two before and one after transplant was 20 months, one patient relapsed 6 months after transplantation, respectively. After a follow up ranging from 2 to allogeneic transplantation; 4 patients had bulky disease and 6 30 months, 31/33 patients are alive and in continuous clinical had BM involvement. In 9 out of 11 patients there were severe remission, one patient died because of progression of disease, comorbidities contra-indicating an heavy salvage CHT, in the one patient relapsed and is now under treatment with other cases this association was started, in one patient because Campath1M. 12 out of 18 FCCL patients and 6 out of 10 CLL of a previous conventional antracyclines cumulative dose ³ 500 patients are also in molecular remission (BCL-2 and VDJ-IgH mg /sqm and in one case for previous mediastinal irradiation. negative, respectively). Finally, 5/5 LPL patients are still in The schedule of protocol included the infusion of two doses of complete clinical remission. Rituximab (RTX) at day 0 and 14 while the PLD was infused at In conclusion, we confirm that use of rituximab during PBSC 30 mg/sqm at day 4 together with CTX 750 mg/sqm; all patients mobilization, in combination with high dose chemotherapy, could received low dose GM-CSF (2.5 mcrg/kg/day) starting from day 5 be not only useful as in vivo purging strategy of autografts, but until the second RTX infusion in order both to up-regulate the also effective in inducing long-lasting remissions in indolent CD20 expression and increase the ADCC. A median number of 4 lymphomas. courses (range 1-6) and 7 RTX infusions (range 2-13) were respectively administered. The protocol was well tolerated; among 34 courses of treatment, we observed only one grade 3-4 P423 acute adverse event (tumor lysis syndrome). Furthermore one Treatment of Hodgkin’s disease with autologous stem cell patient, relapsing after allogeneic transplant, experienced a transplantation: analysis of results and prognostic factors in Steven Johnson syndrome and a grade III aGVHD after a dose 341 patients from the Polish Lymphoma Research Group of PLD and RTX. The grade 3-4 haematological toxicity was 12.8% for anemia, 33.3% for neutropenia and 30.8% for J. Czyz, A. Hellmann, R. Dziadziuszko, L. Kachel, J. Holowiecki, thrombocytopenia. Extrahematological toxicity was negligible and J. Gozdzik, J. Hansz, A. Avigdor, A. Nagler, M. Osowiecki, J. consisted in diffuse dysesthaesias and itch in one patient; only 4 Walewski, W. Knopinska-Posluszny, P. Mensah, W. Jurczak, A. patients had grade 3-4 infections; no treatment related deaths Skotnicki, M. Sedzimirska, A. Lange, W. Sawicki, K. Sulek, M. were observed. Nine patients were evaluable for response: the Wach, A. Dmoszynska, A. Kus, K. Warzocha, T. Robak (Gdansk, response rate was 55.5% with 1 CR and 4 PR. The clinical Katowice, Poznan, PL; Tel-Hashomer, IL; Warsaw, Cracow, outcome, with a median follow-up of 6 months (range: 1-24), Wroclaw, Lublin, Lodz, PL) shows that 6 patients are alive, 4 in CCR (3 CR converted from The use of autologous stem cell transplantation (ASCT) proven PR) and 1 with stable disease; 3 patients died for progressive clinical effectiveness for patients with relapsed or refractory disease. In conclusion this regimen was well tolerated and Hodgkin’s disease. We evaluated long-term outcome in 341 feasible even in this cohort of heavily pre-treated poor prognosis patients who underwent ASCT between August 1990 and March patients, relapsing after transplantation. A longer follow-up is 2002. One hundred sixty seven females and 174 males with a needed but the preliminary results seem to suggest a possible median age of 28 years (range, 16 to 53 years) were evaluated. role for this association in this setting. The indication for ASCT were: primary resistance (n=91), early first relapse (n=51), late relapse (n=57), first partial remission P422 (n=47), subsequent relapses (n=63) or first CR (n=32); 87 patients were resistant to previous chemotherapy. Most patients Sequential high-dose therapy plus rituximab as in vivo received BEAM (50%) or CBV (35%) as a conditioning regimen. purging agent in low grade lymphomas The graft consisted of bone marrow (24%), peripheral blood P. Mazza, A. Prudenzano, G. Pricolo, L. Stani, A. Maggi, B. (72%) or both (4%). Amurri, G. Palazzo, G. Pisapia (Taranto, I) Treatment related mortality was 6%. The 5-year OS was 64% (95% CI, 57% - 71%), 5-year EFS was 45% (95%CI, 39% - Rituximab, an anti-CD20 monoclonal antibody highly efficient in 51%), median EFS was 2.4 years. In the multivariate model three the removal of circulating B-cells from peripheral blood, seems to factors were identified as significant predictors of unfavorable be useful as in vivo purging strategy prior to transplant in patients overall survival: more than two previous chemotherapy lines with lymphoprolipherative disorders, mainly low grade (hazard ratio, HR= 2.16) poor response to previous lymphomas. We therefore initiated a trial that combines chemotherapy (HR=1.67) and disease status at ASCT (PR+CR Rituximab with high dose chemotherapy followed by autologous versus PD, HR=2.15). The same factors significantly predicted stem cell transplantation in 33 patients (10 chronic lymphocytic for unfavorable failure-free survival (HR=1.67, 2.49 and 1.78, (CLL), 18 follicular center lymphoma (FCCL), 5 respectively). Ten patients (2.9%) developed a secondary lymphoplasmacytoid lymphoma) (LPL), 24 of which newly malignancy after transplantation. diagnosed and 9 pretreated. They were 20 males and 13 We conclude that ASCT should be introduced early in the course females and aged from 37 to 70 years (median age 57 yrs). of the disease for selected patients responding to standard Molecular evaluation of IgH-VDJ and of BCL-2 rearrangements, chemotherapy. by PCR techniques, was performed at diagnosis in CLL and FCCL patients, respectively; therefore, subsequent molecular monitoring was performed after transplantation in patients found positive for one of these molecular markers.

S72 P424 two courses of DHAP (5 cases). At the time of ASCT nine patients were in CR, six in PR and four had a RD. After Time scheduling of primary high dose therapy in aggressive transplantation, using BEAM as preparative regimen, 15 patients NHL has significant impact on treatment results: mega- achieved a CR and 4 a PR. Ten patients received further CHOEP dose level 3 - a randomized phase II study mediastinal RT even if they had a minimal (<25%) residual mass B. Glass, M. Kloess, A. Engert, W. Berdel, B. Metzner, L. at computed tomography scan and independently from Ga67 Trümper, M. Löffler, M. Pfreundschuh, N. Schmitz on behalf of scan results. Two out four patients in PR after ASCT died for the DSHNHL MLCL progression, 10 and 14 months from transplantation. At a median follow-up of 42 months (range 6-102) from ASCT the Feasibility and high efficacy of dose escalated CHOP + DFS is 89.5%. We conclude that the outcome following this Etoposide with repeated stem cell transplantation (Mega- programme of intensification with ASCT results in a high CHOEP) in primary treatment of aggressive NHL with risk factor incidence of durable remission even in patients with refractory (elevated LDH) was proven in a dose escalation study (Dose disease. level 1 and 2). Since dose limiting toxicity was not seen in thus previous study, we further escalated dose of cyclophosphamide Comparison of three conditioning regimens used in high- and Etoposide (Dose level 3) in a randomized Phase II study. dose therapy of malign lymphomas: CBV-ICE-CTM Dosage at respective dose levels (DL) were as follows: DL1, E.A. Soydan, M. Arat, P. Topcuoglu, T. Demirer, O. Arslan, M. Cycle1: cyclophosphamide (CY) 1500 mg/m2, adriamycin (ADR) Ozcan, M. Beksac, G. Gurman, O. Ilhan, N. Konuk, H. Koc, A. 70 mg/m2, vincristine 2 mg, Etoposide (ETO) 450 mg/m2, and Uysal, H. Akan (Ankara, TR) prednisone 500 mg/m2.: Cycle II and III : CY 4500 mg/m2 and ETO 600 mg/m2, cycle IV: CY 6000 mg/m2 and ETO 1000 High dose therapy with autologous peripheral stem cell (APBSC) mg/m2. At DL2 ETO was further intensified: 600, 960, 960 and support in malign lymphomas is a current treatment modality with 1480 mg/m2 at cycles 1-4, respectively. At DL3 patients were well-established efficacy for certain indications and is also randomized to a four or six cycle variant of Mega-CHOEP with frequently used in our country as well as in other countries world- the following doses of CY: 1500, 6000, 6000, 6000 mg/m2 ETO wide. There are a quite few number of randomized studies 600, 1480, 1480, 1480 mg/m2 (arm A) vs. CY 1600, 1600, 1600, investigating the effect of stem cell regimen on the short and long 4500, 4500, 6000 mg/m2, ETO 600, 600, 600, 960, 960, 1480 term survival, which has not yet been demonstrated. In our clinic mg/m2 (arm B). From February 97 to May 02, 271 pts were 56 patients with the diagnosis of Hodgkin’s Lymphoma (HL, n:23) enrolled in the study, 47 at dose level 1, 77 at dose level 2, 84 at and non Hodgkin’s Lymphoma (NHL, n:33) who were treated dose level 3 and 63 at dose level 3 + rituximab. Seven cases with HDT and APBSC support. The high dose regimens were (3%) of treatment related mortality did occur. 25 / 45 pts at DL 3A ICE (Ifosfamid 2,5 gr/m2/day 4 days, Etoposid 600mg/m2/day 4 (4 cycles) and 26 / 26 pts at DL 3B (6 cycles) were evaluable for days, Carboplatin 500mg/m2/day 3 days; n=18), CVB efficacy after median observation time of 13 months. Age (Cyclophosphamide 600 mg/m2, Etoposide 600 mg/m2, BCNU adjusted IPI 1-3 was distributed as follows: 21.9%, 40.6%, 37.5% 300 mg/m2 ; n= 22) and CTM (Carboplatin 350-450 mg/m2/day 3 vs 15.4%, 61.5%, 23.1% Median duration of therapy were 102 vs days, Thiotepa 250mg/m2/day 2 days, Melphalan 50mg/m2/day 152 days. Therapy could not be administered regularly in 4 / 25 2 days; n=16). The three groups were similar on the basis of at arm A due to toxicity. At arm B 8 / 26 pts stopped therapy, 4 their age, gender, diagnosis, time from diagnosis to transplant pts due to progress of lymphoma, 2 due to failure of stem cell and transplantation and the disease status at the time of mobilization and 2 due to toxicity. 64% vs. 50% of the patients transplantation. The patients were evaluated according to achieved CR or CRu 3 months after last cycle of therapy. At one transplant-related mortality and short term response (Table). The year, overall survival was 94.1% vs. 60.1% and freedom from gastrointestinal toxicity has been leading in all three regimens treatment failure was 64% vs. 37.4%. Although cumulative and renal toxicity was observed only in ICE. When the three dosage of active agents was grossly the same in both arms, regimens were retrospectively analyzed, their toxicity profiles prolongation of therapy and later intensification in arm B were were similar however the engraftment kinetics were different as followed by inferior results and randomization was stopped. the neutrophil engraftment was observed earlier in the patients Mega CHOEP DL3A (four cycles) is the basis of the current who received ICE and CTM than the patients who received CVB. protocol combining Rituximab with MEGA-CHOEP therapy. This difference was attributed to the use of G-CSF in latter Mega-CHOEP is feasible (DL1-3) and effective (DL 1, 2 and 3A) regimen. In our retrospective comparison we did not find any as primary treatment of aggressive NHL with high risk features. significant difference between 3 different conditioning regimens in terms of toxicity, morbidity, mortality, response and relapse. Additional abstracts to this topic Autologous stem cell transplantation for poor risk primary mediastinal large B cell lymphoma with sclerosis R. Cairoli, G. Grillo, P. Marenco, A. Tedeschi, L. Gargantini, E. Tresoldi, E. Morra (Milan, I) The aim of the study was to evaluate the impact of an intensification programme including autologous stem cell transplantation (ASCT) in patients with mediastinal large B cell lymphoma (MLCL) presenting with adverse prognostic factors. Between 1993 and 2002, 24 patients with MLCL were referred to our institution. Five patients were classified as low risk according to the AA-IPI. Nineteen patients (79%, study group) were categorised in the intermediate-high or high risk group and were considered eligible for ASCT. After induction therapy, consisting of VACOP-B, we recorded among the nineteen poor-risk patients: 7 CR, 7 PR and 5 refractory disease (RD). All these patients received mobilising therapy consisting of high-dose cyclophosphamide (15 cases) or DHAP (4 cases). After peripheral stem cell collection, to obtain a greater tumor mass reduction before transplantation, the 12 patients not in CR received further treatment with high-dose etoposide (7 cases) or

S73 Autotransplant of bone marrow or peripheral hemopoietic nonematologic toxicity was minimal with 10% of severe mucositis stem cells in patients with Hodgkin’s disease refractory or (grade 3 WHO), 2 pts were noted to have hepatic toxicity. No relapsed: a single-center experience other clinical significant toxicities were demonstrated. We A.A. Colombo, C. Baratè, P. Bernasconi, D. Caldera, C. consider the survival starting from the data of stem cells Pascutto, E. Brusamolino, M. Lazzarino, E.P Alessandrino reinfusion and after a median follow-up of 35 months (range 5 – (Pavia, I) 94) 33 pts (83%) are alive and overall survival was 77% at three years, the clinical characterictics statistically significant for High-dose chemotherapy followed by transplantation of survival were early stage (p .01) and pre-ABMT condiction (CR autologous hemopoietic stem cell has become the standard or CR more than one) (p .009). After a median follow-up of 31 approach for most patients with relapsed or refractory Hodgkin’s months (range 1 – 88), 30/40 (75%) pts were freedom from disease(HD). disese, and disease-free survival (DFS) was 72%. The following Between March 1986 and October 2002, 72 patients (pts), characteristics were significantly associated with DFS: earlier median age 29 (range 16-58) years, underwent autologous stem stages (p .01), complete remission at ABMT p .01. In conclusion cell transplant at Bone Marrow Unit of our Centre. At diagnosis we confirm the efficacy of this condictioning regimen and its 16% had stage IV and 31,9% had bulky disease; 58 pts (80%) feasibility in an homogeneous group of patients. received 3 or more regimens before transplant and 45 pts (62%) received radiotherapy. Median time from last chemotherapy and Autologous peripheral blood progenitor cell transplantation high dose regimen was 11 weeks (range 3-34). At transplant 28 in lymphoma patients: early outcome and cell dose pts (38,8%) were in CR, 15 in PR, 16 had stable disease and 13 R. de Paz, M.C. Fernandez-Jimenez, R. Arrieta, M. Canales, F. manifested disease progression; 27% pts were chemo-refractory Hernandez-Navarro (Madrid, E) disease. The graft consisted of bone marrow (22pts) or PSC (50pts); the most frequently high-dose regimen was BVC in Objective: Autologous peripheral blood progenitor cell 54/72 pts and BEAM in 15/72 pts. Median follow-up was 113 transplantation (PBPCT) is being increasingly used in many (range 1-199) months. At 5 years overall survival (OS), event clinical settings. In this study we evaluate the importance of the free survival (EFS), and risk relapse (RR) were 70%, 43% and dose of infused CD34+ cells and mononuclear cells (MNC) on 21%. hematopoietic recovery, transfusion requirement and transplant- In particularly 85% of pts in CR at transplant was alive at 5 years related toxicity after autologous PBPCT. compared to 66% of PR pts, 69% and 59% of pts with stable Patients and methods: We analyzed data from a homogeneous disease or in relapse. We observed three non relapse deaths group of 60 adult patients diagnosed of non-Hodgkin’s lymphoma due to treatment-related complications (TRM 4,1%) that (37) and Hodgkin’s disease (23) who received an autologous appeared at a median time of 2 years after transplant. PBPCT. The conditioning regimen used was BEAC in all Progression of HD occurred in 40% pts (66% pts were stable patients. No post-transplant G-CSF was administered. disease and 45% relapsed pts).The EFS at 5 years was 69% Results: The median numbers of MNC and CD34+ cells infused and 41% in CR and in PR pts; in stable disease or refractory pts were 12.8 x 10e8/Kg (3.3-29.6) and 3.7 x 10e6/Kg (0.76-10.6), was 36% and 29%. respectively. The median time to achieve an ANC greater than Survival was correlated to disease status at transplant; we 0.5 x 10e9/l was 14 days (9-20). Platelet counts reached 20 x observed at 5 years OS of 69% in CR pts and an OS of 41%, 10e9/l and 50 x 10e9/l in a median of 11 and 14 days, 27% and 50% in PR , stable disease, and relapsed pts. respectively. Median transfusion requirements were 3 red cell Chemosensitive status before transplant induce a significant units and 8 platelet units. 15 patients developed WHO grade III- increase of OS: 86% pts defined responding to salvage to IV oral mucositis and gastrointestinal toxicity >= grade 2 chemotherapy were alive at 5 years, versus 58% and 73% for pts occurred in 12%. We found a direct correlation between dose of defined refractory or multiple relapsed; after high dose procedure CD34+ cells infused and speed of engraftment, especially with survived 76% of pts in CR, and only 28% of resistant and 36% of platelet recovery. An infusion of more than 15 x 10e8/Kg MNC multiple relapsed pts. In CR groups pts we observed also a was associated with significant reduction of red cell transfusion better EFS and a minor RR (76% and 0%) compared to EFS and support but not with platelet transfusion requirement, while we RR of resistant and multiple relapsed pts (EFS: 32% and 30%; did not observe a significant correlation between the number of RR 53% and 20%). Our data confirm that HD pts who fail to MNC infused and engraftment. As regards toxicity, there was a respond with first line chemotherapy may benefit from higher incidence of gastrointestinal mucosa toxicity >= grade II in autologous transplantation. patients who received less than 10 x 10e8 MNC/Kg. Grade IV mucositis was associated with higher requirement of both red High-dose ifosfamide, carboplatin and etoposide (Ice) as blood cell and platelet transfusion. conditioning regimen in autologous bone marrow Conclusions: In agreement with previous reports, we observed transplantation in high-grade non-Hodgkin's lymphoma that higher CD34+ cell dose was associated with shorter time to A. Bosi, L. Rigacci, R. Alterini, S. Guidi, A. Carpaneto, R. platelet and neutrophil recovery. Additionally, we noticed a not Saccardi, F. Bernardi, A. Vannucchi, V. Carrai, L. Lombardini, C. well explained association between the number of MNC infused Nozzoli (Florence, I) and the requirement of red blood cell transfusion. Interestingly, we found a relationship between MNC dose and gastrointestinal High dose chemotherapy followed by autologous stem-cell mucosa toxicity. We hypothesized that this relationship might be rescue has been used in non Hodgkin’s lymphoma (NHL) with explained by the role of monocytes in the inflammatory and different indication. We report here the results of ICE (Ifosfamide tissue regeneration. The identified association of grade IV 3000 mg/m2 -6 –5 –4 -3, Carboplatin 500 mg/m2 -6 –5 –4 , mucositis and transfusion support could be due to bleeding Etoposide 300 mg/m2 –6 –5 -4) protocol in a group of high-grade secondary to severe mucosa injury. NHL patients (pts). 40 pts from january 1994 to january 2002 were treated in our institution. A large part of this set of pts had Treatment of a patient with T-cell lymphoma, high risk factors for relapse: 65% presented intermediate-high IPI myeloproliferative disorder and translocation t(8;13) with index and 45% had mediastinic bulky disease. After histological allogeneic bone marrow transplantation in combination with revision according to REAL classification all pts showed large basiliximab cell lymphoma. After the induction or salvage therapy the pre- R. Fenk, T. Emde, P. Schneider, B. Hildebrandt, U.-P. Rohr, A. ABMT clinical state was: 24 first complete remission (CR), 6 Hünerlitürkoglu, U. Steidl, G. Meckenstock, R. Haas, G. Kobbe second or third CR, 4 partial responders and 6 refractory to (Duesseldorf, D) induction therapy. The condictioning regimen ICE was well tollerated: no treatment-related mortality was reported, Coincidence of T cell lymphoma and myeloproliferative disorder in combination with reciprocal chromosomal t(8,13) is a rarely

S74 described syndrome with only 16 cases published to date. proceeded to high dose CT engrafted successfully. Hematopoetic stem cell transplantaion (HSCT) appears to be the Conclusions: Chemotherapy with ISHAP plus G-CSF is only curative treatment option for this disease. We report on a efficacious and safe salvage-regimen for aggressive lymphomas 32-year-old male with t(8;13)(q11;p11) presenting with with good mobilizing capacity. leukocytosis in the peripheral blood, myeloid hyperplasia and eosinophilia in the bone marrow. Four months later the patient Failure to achieve a normal blood count at one year after developed T cell lymphoblastic lymphoma with generalised autotransplantation in lymphoma is only predicted by the lymphadenopathy and splenomegaly without bone marrow quantity of harvested CD34+ peripheral blood stem cell involvement. After treatment according to the GMALL-study J. Manson, N. Mounier, J. Larghero, G. Sergent, P. Brice, N. protocol the patient showed dissappearance of lymphadenopathy Parquet, I. Madelaine-Chambrin, J. Briere, C. Hennequin, M. but persistent bone marrow hyperplasia and translocation. The Benbunan, J.-P. Marolleau, C. Gisselbrecht (Paris, F) patient then recieved unmanipulated bone marrow from an unrelated donor with one molecular HLA-B-mismatch after Autologous Stem-Cells Transplantation (ASCT) is widely used conditioning with melphalan, thiotepa and cyclophosphamide. for lymphoid malignancies as consolidation in chemosensitive For in-vivo T cell depletion as graft-versus-host-disease (GvHD) patients. Despite the low morbidity / mortality incidence of this prophylaxis and concomitent anti-lymphoma therapy ATG and procedure, some patients fail to obtain a complete hematological the anti-CD25 antibody basiliximab was given. Further GvHD reconstitution after one year. prophlaxis consisted of CsA and MMF. Among the 173 consecutive lymphoma patients who underwent Results: Rapid engraftment and conversion to complete donor ASCT with unpurged PBSC in our department from nov. 1995 to chimerism was observed. Despite short-lasting cutaneous GvHD nov. 2000, 133 (78%) were alive without relapse at one year. We °I after reduction of immunsuppressive treatment and a delayed report here the results obtained in 106 patients (59 males and 47 reconsitution of peripheral blood cell counts no major females) for whom hematological data were available at 1 year. complications occurred during follow-up. The patient is off- At diagnosis, 94 patients had Non (42 treatment with an karnofsky-index of 100% and a complete diffuse-large-B-cell, 6 T-cell, 25 follicular, 5 mantle-cell, 3 cytogenetic remission 564 days after transplantation. lymphoblastic, 13 small cell) and 12 Hodgkin Lymphoma. At time Conclusions: Our data confirm that allogeneic HSCT can offer of harvest, median age was 43 [17-66], no patient had marrow cure for patients with the rare t(8;13)-syndrome. In this case the involvement and all were in CR or CRu. Fifty seven patients in-vivo T cell depletion with ATG and basiliximab may play a role (54%) received front line ASCT. After graft, median day to ANC > not only in prevention of severe GvHD in unrelated HSCT but 0.5 G/L was 10 [7-18] and platelets > 50 G/L was 14 [7-58]. After also through targeting of T cell lymphoma cells. 100 days, 54/96 (56%) had none or only 1 hematological lineage completely reconstituted. After one year, Hb count was normal ISHAP as pretransplant salvage and mobilization regimen (13 g/dL) in 47%, leukocytes count (4 G/L) in 77%, platelets for lymphomas count (150 G/L) in 60%. 32/98 patients (33%) had a normal E. Karamanesht, S. Korenkova, S. Borodkin, V. Homenko (Kiev, blood count, 31 patients (32%) had 2 hematological lineages UKR) completely reconstituted, 22 (22%): 1 lineage, and 13 (13%): none. Univariate analysis according to hematological Introduction: ISHAP regimen was introduced as a part of our characteristics are given in the following table. We used Cox clinic transplant protocol in attempt to overcome lymphoma model with smoothing splines to assess the functional form of chemoresistance. On the other hand this regimen must be potent covariates. It demonstrates that the best cut-off for harvested to mobilize sufficient quantities of PBSC. In our study we have CD34+ PBSC was 5. 106/kg (RR=3.06 [1.44-6.48], p=0.0035). evaluated efficiency, safety and mobilizing capacity of ISHAP However, we failed to isolate other independent predictive cytoreductive regimen. factors for normal blood count after one year. Patients and methods: From May 2001 to Nov 2002 22 patients In conclusion, 35 ASCT patients (35%) failed to achieve a normal with relapsed and refractory lymphomas (HD-21 pts and NHL-1 blood count at one year and had a trend to an higher risk of pt) received 1 to 2 courses of ISHAP (total number 39) as death. CD34+ cells > 5. 106/kg is the best prognostic factor for second line chemotherapy. The median age of patients was 29 long term reconstitution after ASCT in Lymphoma. years (range 15-47 years), 10 patients were male and 12 were female. Disease status before salvage was: primary refractory – 9 pts, 1st relapse – 5 pts, >1st relapse - 8 pts. Prior chemotherapy consisted of median 8 courses (range 4-15). Prior radiotherapy had been given to 19 pts (86,4%). ISHAP chemotherapy consists of idarubicin 2-3mg/m2/d IV CI; cysplatinum 25mg/m2/d IV CI over 96h, days 1 to 4; methylprednisolone 500mg/d IV, days 1 to 5; cytosine arabinoside 1,5g/m2/d IV on day 5. PBSC collection was performed after first or second course of ISHAP plus G-CSF (5- 10mcg/kg from the day +7 after the end of CT). Minimum dose of CD34+cells was determined as >2x106/kg. Results: Minimal WBC (range 0,1-4,45x109/L) were seen at day +5 to +9 (median +8). Neutropenia (ANC<500/mcL) was seen in 5 pts (22,7%). 3 pts had fever during neutropenia. Platelets Mini-BEAM polychemotherapy + G-CSF is superior to <20x109/L were seen in 3 pts (13,6%). Only one pt needed 1 Cyclophosphamide alone +G-CSF priming for peripheral platelet transfusion, RBC were transfused in 3 cases. Nausea blood stem cell collection for autologous stem cell and vomiting were observed at the end of CT course and were transplantation in patients with malignant lymphomas mild to moderate. There were no deaths in consequence of toxicity. Response rate (CR + PR) was 68%. PBSC collections H. Minigo, A. Planinc-Peraica, S. Ostojic Kolonic, D. Radic were performed in 20 pts between day +13 and +18 (median Kristo, N. Turk, K. Baric-Besis, C. Maglov, M. Strauss-Patko, Z. +15) from the end of CT. PBSC were harvested after 20 ISHAP Siftar, M. Kardum, I. Kardum-Skelin, R. Vrhovac, R. Kusec, V. courses with median 2 (range 1 to 4) aphereses per collection. Japec, O. Jaksic, B. Jaksic (Zagreb, HR) PBSC yield: CD34+cells – 12,9x106/kg (range 0,4–65,6 Background: Cyclophosphamide (CPM) alone (3-5g/m2) + G- x106/kg), MNC – 7,1x108/kg (range 1,4–12,6 x108/kg). Two pts CSF is accepted as standard for priming and PBSC collection in failed to collect adequate CD34+ dose. All 18 pts who were patients with malignant lymphomas (ML). To test

S75 chemosensitivity to drugs to be used for myeloablative (BEAM) therapy. In the aggressive lymphoma group 7/9 relapsed pts. conditioning and to collect stem cells in recovery phase we used have died due to the underlying disease. MB + G-CSF. Preparative treatment with BEAM or BEAC results in a high Objectives: to compare efficacy and safety of CPM versus Mini- remission rate. In aggressive lymphoma, relapse occurs early BEAM polychemotherapy (MB) for priming in otherwise identical after transplantation and is not sensitive to salvage therapy. In autologous stem cell transplantation (ASCT)in ML patients. FL, relapse occurs later with a continuing pattern and even after Patients and methods: 107 pts with ML including 67 NHL, and 40 56 months. HL patients (57 M, 50 F; median age 36 (17-67), were treated by We conclude, that chemotherapy with BEAM or BEAC only has ASCT following BEAM myeloablative treatment. To collect no curative potential as preparative regimen in pts. with relapsed peripheral blood stem cell (PBSC) 33 patients were primed by or refractory follicular lymphoma. Addition of radiotherapy or CPM +G-SCF, while 74 received MB+G-CSF. For both groups radioimmunotherapy to high dose treatment may optimize the G-CSF was started (5 mgr/kg), as soon as WBC dropped below treatment results. In aggressive lymphoma pts., risk factors for 1x109/L, and maintained during leukaphereses. Over 96% of early relapsing pts. have to be identified. For those pts., the patients had active disease at time of transplantation. All pts preparative regimen has to be improved, e.g. by addition of received heavy prior treatment with a median of 2 lines of monoconal antibodies. chemotherapy (range 1-6) and median of 8 chemotherapeutic cycles (range 2-31). Efficiency of in vivo purging with autologous stem cell Results: Both groups were fully comparable for demographic and transplantation and rituximab in B-CLL non-Hodgkin's disease related characteristics. However, significant difference lymphoma was observed in total number of CD34+ collected cells (mean E. Tothova, N. Stecova, A. Kafkova, T. Guman, M. Fricova, E. 4,7 for CPM versus 14,7 for MB, p<0.0001) and in average Svorcova (Kosice, SK) number of CD34+ cells per leukapheresis (1,734 versus 10,722; p<0.0020); average number of leukaphereses (2.2 versus 1.6; Background: To prevent contamination of the reinfused stem p<0.0039); No difference is observed in average mononuclear cells, several investigators have attempted to purge the count collected between groups (3,76 x108/kg versus 3.79 harvested stem cells of malignant cells before reinfusion into the x108/kg; NS). In post transplant period, the significant difference patients (pts). Rituximab, an anti- CD 20 monoclonal antibody, is was observed in time to WBC recovery to more then 1x109/L specific for the B-cell surface antigen and can be used in (average 11.6 versus 9.5; p<0.0001), platelet recovery to more autologous stem cell transplantation (ASCT) to eliminate then 20x109/L (13 versus 11; p<0.0298); need for platelet lymphoma cells before harvest (in vivo purging) or to prevent transfusions (average doses 17.1 versus 12.7; p<0.0231) and regrowth of malignant cells following transplant (post-transplant days of G-CSF treatment (average 9.7 versus 7.9; p<0.0001). therapy). Overall response rates were (CR 70,1%; PR 26,2%) with no Methods: Our study was conducted in 37 consecutive pts with difference between groups. Overall projected survival at 9 years untreated CD 20 positive B-NHL (follicular lymphoma-9, chronic was 54.3% and DFS 55.7%, with no difference between groups. lymphocytic leukemia-16 and NHL in leukemic phase- Conclusions: MB proved superior to CPM in priming for ASCT in 12).Patients received 4 courses of standard-dose chemotherapy patients with ML in terms of significantly higher yield of CD34+ (CHOP or FLU-CY) followed by one course HDT plus G-CSF cells (in equal number of mononuclear cells), significantly less (HDT). Patients allocated to Rituximab (n=19) received number of leukapheresis needed, faster hemopoietic recovery i.v.infusion of 375 mg/m2 48 hours before stem cells collection post-transplant. Response rate, TRM, overall survival and DSF and in 3 weekly doses after transplantation (R-HDT). were virtually identical in both groups. For this reason we Results: The rate of complete response was significantly higher recommend MB for stem cell collection priming in ML patients in the R- HDT group than in the group that received HDT alone undergoing ASCT. (76% vs 59%, p=0.005). Median follow-up two years, event free and overall survival times were significantly higher in the R-HDT High-dose chemotherapy with BEAM or BEAC in relapsed or group (p<0.001 vs p=0.002), respectively.Yield of purged CD34+ refractory follicular and aggressive lymphoma cells was with median 5,23x10/6/kg in HDT and 7,76x10/6/kg in M. Sandherr, R. Peter, E. Stattenberger, C. von Schilling, C. R-HDT pts. Clinicaly relevant toxicity was not significantly greater Peschel (Munich, D) with R-HDT gruop. No significant difference was observed between HDT and R-HDT group in the mean number of days High dose therapy with autologous stem cell support has spent with neutropenia and trombocytopenia. become standard treatment in relapsed or refractory follicular Conclusion: The addition of Rituximab to the transplant regimes and aggressive lymphoma. The optimal preparative regimen has produced clinical and molecular remission in 76% of evaluable still to be determined. We have retrospectively analysed the data pts and allowed the harvesting of large amounts of tumor free of all our patients who have had chemotherapy with BEAM or progenitor cells without a clinicaly significant increase in toxicity. BEAC. At our institution, 39 patients have been treated with BEAM or Thalidomide-induced remission of refractory diffuse large B- BEAC followed by autologous stem cell support since 09/97. Two cell lymphoma post-allogeneic SCT - a result of modulation have been lost to follow-up. The median follow up was 27 of CTL function? months (range 3-60) for all other 37 pts. Histology was S. Tueger, F. Chen, G. Ahsan, V. Andrews, M. Kazmi , J. aggressive lymphoma in 21 pts., mantle cell lymphoma (MCL) in Madrigal, S. Schey (London, UK) 2 pts. and follicular lymphoma (FL) in 14 pts. All pts. had refractory or relapsed disease. A 36 year old man with primary bone marrow diffuse large B-cell The overall response rate (ORR) was 93% in FL (CR 71%) and lymphoma (DLCL) in second relapse underwent autologous stem 91% in aggressive lymphoma (CR 52%). There were 14 deaths: cell transplantation with BEAM and Interferon/ ciclosporin for 4/14 in FL pts. (1 toxic, 3 due to lymphoma) and 10/23 in the induction of autoreactive GVHD (BNLI trial). However, his other group (1 sAML, 9 lymphoma). disease remained refractory and after salvage treatment with 2 Relapse occured in 16 pts.: in FL 54% have relapsed after a courses of CHOP-Rituximab, he received an HLA-matched median of 20 months (range 12-56), with a continuing pattern of allograft using Cyclo/TBI conditioning. Restaging at 3 months relapse. In aggressive lymphoma pts. 43% have relapsed after a post-allograft showed resolution of bone marrow disease but the median of 5 months (range 1-9) without any late relapses. All appearance of bilateral adrenal masses, confirmed as relapsed MCL pts. have relapsed. disease on biopsy. Despite discontinuing immunosuppression, Survival after relapse was different: in the FL group 3/7 relapsed the disease progressed with cervical lymphadenopathy and pts. have died while 4/7 are alive and in remission after salvage testicular swelling.Single agent thalidomide at 200 mg daily was commenced which led to complete regression of his neck nodes

S76 and a decrease in testicular swelling within 48 hours. The patient P426 continues on thalidomide 50 mg daily 14 months following his allogeneic transplant and remains in remission. Total cumulative dose of cyclophosphamide administered Analysis of antigen-specific T-cell reconstitution post transplant during induction infusional chemotherapy (C-VAMP) is an in this patient prior to receiving thalidomide showed less than independent prognostic marker in new patients with 35% of CMV-specific CTL’s, as identified by CMV-specific HLA myeloma tetramers, were functional in terms of perforin synthesis. As a B. Sirohi, R. Powles, S. Singhal, S. Kulkarni, C. Horton, C. surrogate for antigen specific immune responses, the dysfunction Rudin, J. Treleaven, S. Sankpal, J. Mehta (Sutton, UK) of CMV-specific CTL may reflect similar functional impairment of the patient's lymphoma-specific cellular immunity, which may We have shown that an absolute dose of Cyclophosphamide 500 have contributed to disease relapse in this patient. The addition mg given on day 1, 8 and 15 of a 21 day cycle of infusional of thalidomide may have enhanced CTL function through an chemotherapy with vincristine, doxorubicin, methylprednisolone immunomodulatory effect. (VAMP) results in significantly higher complete remission (CR) This case highlights the remarkable ability of single agent rates in new patients with myeloma (Raje et al, Br J Haematol, thalidomide at low doses to induce responses in patients with 1997;97:153-160) and also improves event-free survival (EFS) in highly aggressive lymphoma who have failed allogeneic patients with light-chain myeloma (Sirohi et al, Bone Marrow transplantation. Transplant, 2001;28:29-37). C-VAMP is administered till maximum response (defined as attainment of CR or stable plateau) and some patients may receive upto 8 courses with 9g Physicians Poster Session: Multiple of Cyclophosphamide delivered in 18 doses over 18 weeks. This analysis was undertaken to see if the cumulative dose of myeloma cyclophosphamide administered to new patients with myeloma during C-VAMP had an impact on long-term outcome. Between P425 2/86 and 12/01, 274 previously untreated patients (age 30-84y, median 54; 98F, 176M, 73% stage III disease;61% IgG) received Long-term outcome of myeloma patients treated with an a median of 5 (range, 1-12) courses of C-VAMP. The median elective single autograft with follow-up (5 years): results albumin at start of C-VAMP was 35g/L (16-52); median comparable to tandem autotransplantation creatinine 94 micromol/L (41-1614), medianB2M 3.7 mg/L (0.6- B. Sirohi, R. Powles, S. Singhal, S. Kulkarni, R. Saso, C. Horton, 48.6) and median marrow plasma cell percentage 28%(0-100). J. Treleaven, J. Mehta (Sutton, UK) The white cell count had to be >2x109/L and platelet count >100x109/L for cyclophosphamide administration, hence most Certain groups strongly advocate tandem transplantation in patients did not receive all scheduled doses of myeloma. We have shown that overall survival with single cyclophosphamide (median number of doses given was 67%, autografts (Sirohi et al. Proc ASCO 2002;21:269a) is comparable range 5-100%). The median number of cyclophosphamide doses to tandem transplantation (Barlogie et al. Blood 1999;93:55-65). administered were 9 (1-24) with the median cumulative doses of This study was undertaken to compare the long-term outcome of cyclophosphamide administered being 4.5g (500mg-12g). The patients initially treated with single autografts to those intended median of average number of cyclophosphamide given per C- to receive tandem transplantation. at Little Rock(Tricot et al. Br J VAMP was 2 (1-3). The median overall survival (OS) for patients Haematol 2002;116:211-7). Between 2/1985 and 10/2001, 451 receiving >=4.5g of cumulative dose of cyclophosphamide myeloma patients received a single autotransplant after 200 (n=145) was 6y (0.3-13) compared to 3.7y (7d-13y) for those mg/m2 melphalan. For this study, the 277 patients transplanted 5 receiving <4.5g (P=0.001); the median event-free survival (EFS) years prior to 21 August 2002 were included. The median age for those receiving >=4.5g of cyclophosphamide was 2.9y (0.2- was 50 years (range, 31-69; 54% 50), 16% had IgA disease, and 13) compared to 1.9y (6d-13y) for those receiving <4.5g. Cox 76% had stage III disease. The median B2M and albumin at analysis showed that patients who received >=4.5g of cumulative transplant were 2.3 mg/L (0.1-16.4; 40% >2.5) and 39 g/L (22- cyclophosphamide (RR 0.6, P=0.002), those with B2M < 3.7 (RR 48; 44% 40). The patient population was comparable to that of 2.1, P<0.0001) and those <54y (RR 1.5, P=0.02) had a the Little Rock group. In the Marsden group 76% patients were significantly better overall survival. These data suggest that stage III compared to 48% . The median OS and EFS of the intensification of infusional chemotherapy by the addition of Royal Marsden group were 5.9 years (10days -16y) and 2.3 y(10 weekly cyclophosphamide is an appropriate step in treatment of d-16) vs 2.5 y and 1.5 y respectively. The 7-year OS and EFS myeloma patients. was 42%/22% for the Marsden group versus 31%/18% for the Little Rock group. Of the 55 Marsden patients surviving event- P427 free currently, 22 have a follow-up of >=8 years and 13 >=13 years. A subgroup of 71 patients (26%) with albumin and B2M Serum-free light chain assessment in myeloma patients who <2.5 had a median OS of 8.6 years, compared with 2.3 years for are in complete remission by immunofixation the 31 patients with albumin <35 and B2M 2.5, and 5.4 years for B. Sirohi, R. Powles, S. Kulkarni, S. Sankpal, H. Carr-Smith, J. the remaining 171 patients (P=0.0002)-figure These data Iqbal, A. Bradwell, A. Boast, J. Treleaven, J. Mehta (Sutton, UK) suggest that long-term results of single and double transplants appear comparable. Monoclonal paraproteins in myeloma are assessed by electrophoresis and immunofixation. These techniques are of limited value in following patients with non-secretory or hyposecretory disease. Recently, a serum free light chain (FLC) assay has been developed for following patients in whom standard assays are inadequate. We used the FLC assay (The Binding SIte Limited) to measure light chains in the sera of myeloma patients who were in complete remission (CR) by negative serum immunofixation. 45pts (36-69 y, median 54; 26M, 19F) were studied at a median of 2.8y after high-dose therapy and autotransplantation. The CR duration in these patients was 79-6420d (median 585). The normal range for serum FLC was established by assaying free kappa and lambda in 282 normal subjects (Clark et al, Clin Chem 2001; 47:6 A27). The 95

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