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Autologous Hematopoietic Stem Cell Transplantation for Intravascular Large B-Cell Lymphoma: the European Society for Blood and Marrow Transplantation Experience

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Autologous Hematopoietic Stem Cell Transplantation for Intravascular Large B-Cell Lymphoma: the European Society for Blood and Marrow Transplantation Experience Bone Marrow Transplantation (2017) 52, 650–652 © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 0268-3369/17 www.nature.com/bmt LETTER TO THE EDITOR Autologous hematopoietic stem cell transplantation for intravascular large B-cell lymphoma: the European Society for Blood and Marrow Transplantation experience Bone Marrow Transplantation (2017) 52, 650–652; doi:10.1038/ hematopoietic stem cell transplantation (autoHSCT) has been – bmt.2016.339; published online 19 December 2016 reported to result in a more favorable outcome in single cases7 14 and small case series, almost exclusively in patients of Asian origin (Supplementary Material). In detail, in the pre-rituximab era, two 5 4 Intravascular lymphomas are rare lymphoproliferative disorders out of four and five out of seven autografted patients with IVLBCL were described to survive without relapse. After introduc- characterized by the selective growth of malignant lymphoid cells 6 15 within the lumina of small vessels. On histological and immuno- tion of rituximab, seven out of seven and six out of six patients histochemical examination, around 90% of reported cases meet have been reported to remain alive and relapse-free after 1 autoHSCT. the criteria of large B-cell lymphoma and are categorized into a fi distinct entity in the WHO classification under the designation The objective of the present study was to analyze for the rst time the efficacy of autoHSCT for IVLBCL in a larger cohort of intravascular large B-cell lymphoma (IVLBCL).2 Although IVLBCL Western patients in the rituximab era. can involve extranodal sites in virtually any organ, skin and central This was a registry-based retrospective multicenter study nervous system are predilection sites in Western countries, including patients aged 18 years or over with histologically whereas Asian patients more often present with involvement of fi 1,3,4 veri ed IVLBCL who underwent autoHSCT between 1 January bone marrow, liver and spleen. The presence of isolated 2002 and 31 December 2013, and were registered with the cutaneous lesions is associated with a better outcome,5 whereas 1 European Society for Blood and Marrow Transplantation database. central nervous system IVLBCL has particularly poor survival. Patient’s informed consent was obtained locally at the time of Treatment recommendations for IVLBCL are largely based on autoHSCT. Baseline information and transplant data of eligible retrospective studies and case reports. The combination of patients were downloaded from the European Society for Blood rituximab and cyclophosphamide, doxorubicin, VCR, and predni- and Marrow Transplantation database. Centers were contacted to sone (R-CHOP) is widely used as first-line therapy, but with a PFS at provide updated follow-up information as well as to submit the 2 years of only 50–60%6 outcome is inferior to non-intravascular original written diagnostic report. diffuse large B-cell lymphoma. The primary end points studied were overall survival (time from To improve outcome, more intensive treatment approaches autoHSCT to death from any cause) and PFS (time from autoHSCT have been pursued in individual patients. Autologous to relapse/progressive disease or death from any cause, whatever Table 1. Patient characteristics and outcome n Age Involvement at LDH at First-line Treatment Time from Disease High-dose regimen Time from Follow-up since Cause of death (years), diagnosis diagnosis treatment lines diagnosis status autoHSCT autoHSCT sex at before to at to relapse (months) diagnosis autoHSCTa autoHSCT autoSCT (months) (months) 1 60, f Lung NA R-CHOP 1 7 CR LACE — 5, dead HSCT related (viral infection) 2 48, m CNS Elevated R-CHOP 1 4 CR BEAM — 34+, alive in CR 3 52, m Lung, BM Elevated R-CHOP 1 11 CR TBI 12 Gy, — 95+, alive in CR +R-DHAP cyclophosphamide 4 65, m Spleen, BM Elevated R-CHOP 3 31 CR BEAM 27 30, dead Progression 5 55, m CNS, kidney, gut Elevated HCVAD 1 5 CR TBC — 62+, alive in CR 6 56, m CNS, adrenal gland NA R-CHOP 110CRTBC — 11+, alive in CR +MTX 7 49, f Lung Elevated R-CHOP NA 6 CR BEAM — 51+, alive in CR 8 51, m Spleen, LN, BM Elevated R-CHOP 2 5 PR Mitoxantrone, 15 27, dead Progression melphalan 9 63, m CNS, bone Elevated R-CHP 2 4 PR Carmustine, — 46+, alive in CR thiotepa 10 34, f Liver, spleen Elevated R-CHOP 1 4 CR BEAM — 77+, alive in CR 11 60, f CNS, spinal cord, Elevated R-CHOP 1 8 PR BEAM — 51+, alive in CR lung +MTX Abbreviations: autoHSCT = autologous hematopoietic stem cell transplantation; autoSCT = autologous stem cell transplantation; BEAM = carmustine, etoposide, cytarabine and melphalan; BM = bone marrow; CHOP = cyclophosphamide, doxorubicin, VCR, and prednisone; CHP = cyclophosphamide, doxorubicin and prednisone; CNS = central nervous system; DHAP = dexamethasone, high-dose cytarabine, and cisplatin; f = female; HCVAD = cyclopho- sphamide, VCR, doxorubicin, dexamethasone, methotrexate and cytarabine; LACE = lomustine, cytarabine, cyclophosphamide and etoposide; LDH = lactate dehydrogenase; LN = lymph node; m = male; MTX = methotrexate; NA = not applicable; R = rituximab; TBC = thiotepa, busulfan and cyclophosphamide. aMultiple regimens administered at short intervals in chemosensitive disease in the absence of disease progression in the interval between the individual regimens are considered as a single line. Letter to the Editor 651 a After a median follow-up of surviving patients for 51 months (range 11–95), eight patients were alive and free of progression. 100 One patient (transplanted in first remission) died treatment- related, whereas relapse occurred in two patients, 15 and 80 27 months post autoHSCT, respectively, both with more than one previous treatment line. Two-year PFS and overall survival 60 were 81% and 91%, respectively (Figure 1). This is the first case series on autoHSCT in Western patients with IVLBCL in the rituximab era. Although Western patients have been 40 reported to differ from Asian patients with IVLBCL in terms of clinical patterns,1,3,4 the outcome of our patient cohort with a 20 2-year PFS of 82% is in line with that of autoHSCT in Asian case series,4,6,15 but compares well with the 2-year PFS of 56% after 0 standard R-CHOP.6 Of note, none of the patients autografted in Event-free survival probability (%) 0 24 48 72 96 first remission had disease recurrence in our series despite central Time (months after autoHSCT) nervous system involvement in four of them. The main limitation of our study obviously lies in its retro- b spective nature and the small sample size. However, owing to the 100 rarity of IVLBCL, a prospective randomized trial on a larger number of patients will hardly be feasible. Moreover, an aggressive treatment approach including autoHSCT may not be tolerable 80 by elderly unfit patients, whereas the median age of IVLBCL patients is beyond the sixth decade.4,5 Nevertheless, autoHSCT is 60 manageable in patients up to an age of 65–70 years and thus in roughly half of all IVLBCL patients. 40 In conclusion, these data suggest that early autoHSCT may improve the results of standard induction chemoimmunotherapy 20 in this rare high-risk diffuse large B-cell lymphoma subtype in patients up to an age of 65–70 years. Overall survival probability (%) 0 0 24 48 72 96 CONFLICT OF INTEREST Time (months after autoHSCT) The authors declare no conflict of interest. Figure 1. Event-free survival (a) and overall survival (b) from the time of transplant of 11 patients with autologous hematopoietic stem cell transplantation for intravascular large B-cell lymphoma ACKNOWLEDGEMENTS (Kaplan–Meier curves). autoHSCT = autologous hematopoietic stem We thank all European Society for Blood and Marrow Transplantation centers that cell transplantation. A full color version of this figure is available at participated in this study. the Bone Marrow Transplantation journal online. J Meissner1, H Finel2, S Dietrich1,2, A Boumendil2, E Kanfer2,3, comes first). Secondary end points were incidence of relapse or G Laboure2,4, M Abecasis2,5, J Cornelissen2,6, J Delage2,7, J Finke2,8, progression, and non-relapse mortality (death from any cause U Hess2,9, H Ludwig2,10, M Mohty2,11, T Pabst2,12, P Pioltelli2,13, other than relapse or progression). Survival curves for overall S Robinson2,14, P Samaras2,15, S Montoto2,16 and P Dreger1,2 survival and PFS were calculated by the Kaplan–Meier method. 1Department of Medicine V, University of Heidelberg, A complete data set including follow-up data and the written Heidelberg, Germany; diagnostic report could be retrieved for 19 patients from the 2European Society for Blood and Marrow Transplantation European Society for Blood and Marrow Transplantation database Lymphoma Working Party, Paris, France; who met the eligibility criteria. After exclusion of eight patients 3Department of Haematology, Hammersmith Hospital, with a diagnostic report not confirmatory of the diagnosis of London, UK; 4 IVLBCL, the final cohort for analysis consisted of 11 patients Service d'Hématologie et thérapie cellulaire, Centre Hospitalier (Table 1). The median age at diagnosis of the 11 patients was 55 Universitaire des Bordeaux, Bordeaux, France; 5 years (range 34–65). All had stage IV disease with central nervous Serviço de Hematologia, Instituto Portugues Oncologia, fi Lisbon, Portugal; system involvement in ve patients, lung involvement in four 6 patients, as well as bone marrow and spleen involvement in three Department of Hematology, Erasmus MC-Daniel den Hoed Cancer patients each. Although complete data to assess the International Centre, Rotterdam, The Netherlands; 7Départment d'Hématologie Clinique, Centre Hospitalier Universitaire Prognostic Index were not available, advanced stage along with Lapeyronie, Montpellier, France; elevated LDH in almost all patients suggests an overall unfavor- 8 fi Klinik für Innere Medizin I, University of Freiburg, Freiburg, Germany; able risk pro le as per International Prognostic Index for this 9Klinik für Onkologie/Hämatologie, Kantonspital, patient population.
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