Reduced-intensity allogeneic stem cell transplantation for diffuse large B-cell lymphoma: Clinical evidence of a graft-versus-lymphoma effect

Abstract

6546 Background: Despite being the most common non-Hodgkin’s lymphoma, there have been no specific reports on the use of reduced-intensity (RI) allogeneic stem cell transplantation (alloSCT) to treat patients (pts) with diffuse large B-cell lymphomas (DBCL). This may be due to a lack of definitive evidence for a therapeutic graft-versus-lymphoma (GVL) effect against DLBC. We undertook a retrospective analysis to assess clinical outcomes and evidence of a GVL effect in DLBC pts undergoing RI alloSCT. Methods: The analysis was limited to 18 pts with primary refractory (n = 6) or relapsed (n = 12) DLBC. The median age was 43 years (range: 31–61); median number of previous treatments was 3 (range: 2–9). Nine (50%) pts had undergone autologous transplantation. Three (16%) pts were determined to have chemo-sensitive disease to last treatment prior to RI alloSCT. All pts received a RI conditioning regimen consisting of fludarabine (30 mg/m2/d × 4d) and cyclophosphamide (1200 mg/m2/d × 4d) followed by a T-cell replete allograft from HLA-matched siblings. Results: Median potential follow-up from transplant is 43 months. Seven (39%) pts developed grade II-IV acute GVHD. Response at day +100 post-transplant was as follows: complete response (CR/CRu) = 5; partial response = 5; progressive disease = 8. Nine of 17 (53%) evaluable pts developed chronic GVHD. Median progression-free survival (PFS) was 4.8 months; however, PFS after 9 months post-transplant was 31% with 5 pts in continuous CR/CRu > 12 months post-transplant. Among 14 pts who were not in CR/CRu (n = 12) or progressed after achieving a CR/CRu (n = 2) at day +100 post-transplant, 8 (57%) subsequently achieved a CR/CRu after removal of immune suppression and/or donor lymphocyte infusion (DLI) ± chemotherapy. Seven of these 8 pts remain in continuous (median = 34 months; range: 6–55+) CR/CRu without further treatment. Median survival for all 18 pts was 19 months with survival probability of 40% plateauing at 25 months post-transplant. Conclusions: The clinical observations of sustained CR/CRu after withdrawal of immune suppression and DLI suggest that a GVL effect exists against DLBC. RI alloSCT should be considered as a treatment option for pts with primary refractory and relapsed DLBC. No significant financial relationships to disclose.