Comparison of Unrelated and Sibling Donor Allogeneic Hematopoietic Cell Transplantation (HCT) for Follicular Lymphoma (FL) - From the Lymphoma Working Party, European Group for Blood and Marrow Transplantation (EBMT) and Center for International Blood and Marrow Transplant Research (CIBMTR).

Abstract 874

Allogeneic HCT is potentially curative in FL, but wide adoption of this treatment is limited by its toxicity and donor availability. Improvements in HLA-matching have improved the safety of unrelated donor (URD) HCT. We compared the outcomes of 702 recipients of allogeneic HCT for FL (198 URD and 504 sibling donors (sib)) from 171 centers world-wide reporting to the CIBMTR or EBMT between 1997 and 2005. Recipients of mismatched, cord blood or ex vivo T-cell depleted grafts were excluded. Overall and progression-free survival (OS and PFS), transplant-related mortality (TRM) and relapse/progression outcomes were analyzed using Cox proportional hazards regression models with donor type (sib vs. URD) as the main effect. URD HCT was performed more frequently after 2001. Comparing to the sib group, URD HCT recipients were more likely to receive reduced intensity conditioning (70% vs. 54%), antithymocyte globulin or alemtuzumab (in vivo T-cell depletion) or tacrolimus-based graft-versus host disease (GVHD) prophylaxis, and have a longer interval from diagnosis to HCT (median 49 vs. 32 months). URD HCT recipients had poorer risk FL with more pre-transplant chemotherapy, including previous autologous HCT (36% vs. 16%) and prior exposure to rituximab (66% vs. 43%) compared with sib HCT recipients. Adjusted probabilities for three-year PFS and OS were 49% vs. 60% (p=0.02) and 54% vs. 69% ( p<0.001) for URD and sib HCT, respectively. Cumulative incidence of acute GVHD (grade 2-4) at day 100 was 48% and 42% (p=0.3), whereas chronic GVHD at one year was 47% and 41% (p=0.3) for the URD and sib HCT respectively. Relative risks for TRM, relapse/progression, treatment failure and mortality, comparing URD to sib donors, are shown below. Significant risk factors associated with worse outcomes included poor performance status at transplantation and extensive pre-transplant therapy (> 4 lines of therapy or prior autologous HCT). Additionally, in vivo T-cell depletion was associated with a higher risk of relapse/progression and treatment failure. Reduced intensity conditioning was associated with lower TRM, but did not impact other outcomes. In conclusion, this study shows that URD HCTs are performed later in the treatment course for FL, in higher risk patients, most commonly with reduced intensity conditioning, and are associated with worse PFS and OS compared to sib HCT. Considerations for future studies include the use of URD allogeneic HCT earlier in the course of treatment for FL and avoiding T cell depleting agents in the conditioning regimen.