Reduced-Intensity Conditioning (RIC) Regimen Followed by Allogeneic Stem Cell Transplantation (alloSCT) for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLCL). A Retrospective Study from the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC) Registry.
Authors: Sirvent Anne , Hummelsberger Michael , Chir Zina , Dhedin Nathalie , Faucher Catherine , Jouet Jean-Pierre , Attal Michel , Chevalier Patrice , Robin Marie , Tabrizi Reza , Bordigoni Pierre , Bourhis Jean-Henri , Buzyn Agnes , Contentin Nathalie , Cornillon Jerome , Garban Frederic , Michallet Mauricette 
Published: October 2019

Abstract
Despite progress in their primary therapy, nearly half of patients (PTS) with DLCL will either relapse or fail to archieve a remission. Autologous transplantation may salvage those PTS with chemosensitive disease. However, PTS with high-risk disease or relapsing after autologous transplantation have a particularly poor prognosis. AlloSCT with RIC offers the advantage of a decreased transplant-related mortality combined with a Graft-versus-Lymphoma effect explaining its increasing use in PTS who fail standard therapy. We retrospectively analyzed all PTS with DLCL reported to the SFGM-TC registry, who underwent alloSCT after RIC. 51 PTS (median age 42 years, range 22 to 64 years) were transplanted from Oct. 2002 to Oct. 2004. 23% of PTS had received > 2 lines of prior therapy and 78% had relapsed after autologous transplantation. For 22% of PTS, alloSCT was the first graft. Median time from diagnosis to alloSCT was 33 months (6–126). Disease status at time of alloSCT was: complete remission (CR) n=22, partial remission (PR) n=18, stable disease (SD) n=2, progressive disease (PD) n=7. RIC consisted of fludarabine + busulfan in 27 PTS, fludarabine + total body irradiation in 10, fludarabine + cyclophosphamide in 7 and miscellaneous combinations in 7. GVHD prophylaxis consisted of cyclosporin A (CyA) alone in 18 PTS, CyA/methotrexate in 14 PTS, CyA/mycophenolate mofetil in 14 PTS and other immunosuppressive drugs in 5 PTS. 31 PTS received antithymocyte globulin. Stem cell source was peripheral blood stem cells in 43 PTS and bone marrow in 8. 47 donors were HLA-matched siblings, 4 were unrelated (3 donors HLA-matched and 1 donor with 1 HLA antigen mismatch). Median follow-up after alloSCT was 12 months (0–72). All PTS engrafted except one who died early after transplantation. Grade II to IV acute GVHD occurred in 16 PTS and extensive chronic GVHD in 8/43 valuable PTS. Non relapse mortality was 21% (multi-organ failure : 3, acute GVHD : 1, chronic GvHD : 1, interstitial pneumonia : 1, infection : 4, neurological complication : 1, unknown origin : 1). 20 PTS progressed after a median follow-up of 4.5 months (0–29) and 10 PTS died of progressive DLCL. 23 PTS remain alive and disease-free at a median follow-up of 17 months (1–72). Overall survival is 48% at 22 months. We observe a trend for better survival without statistical significance in PTS who received alloSCT as first graft compared to >1 graft. In PTS in CR or PR prior to transplantation, Kaplan-Meier analysis demonstrates a nearly significant trend for better survival compared to non-responders (55 vs. 28%, p=0,09), but it has to be noted that 3 of 7 PTS transplanted with PD are still alive. RIC followed by alloSCT seems to be feasible even in heavily pretreated PTS and offers the perspective of long lasting remission. Further prospective studies with RIC and alloSCT earlier in the disease course or in defined high-risk PTS in first relapse as an alternative to autologous transplantation should be undertaken.