The Graft-Versus-Lymphoma Effect in Diffuse Large B-Cell Lymphoma

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoma in the adult population, representing 25-35% of new non-Hodgkin lymphoma cases each year (Cultrera & Dalia, 2012). Autologous hematopoietic stem cell transplant (HSCT) is the standard of care after relapse following conventional treatment, with a curative potential of 25-50%, but recurrences are common. Allogeneic HSCT represents a salvage option through the benefit of graft-versus-lymphoma effect. The role of allogeneic HSCT in patients with advanced DLBCL still remains to be defined. In this analysis we evaluated the outcomes of allogeneic HSCT in a group of patients with advanced, high risk DLBCL, and risk factors associated with relapse and mortality.

Methods: The data was obtained through the University of Michigan Blood and Marrow Transplant Program database, under an IRB-approved protocol. Demographics, risk factors, and outcomes were evaluated for all patients with DLBCL who received an allogeneic transplant between 1996 and 2013.

Results: A total of 112 patients were transplanted between 1996 and 2013. Of these, 33% (n=37) transformed from follicular type, 30% (n=31) had an extranodal component, and 36% (n=40) had bone marrow involvement. Twenty-three (20.5%) patients had a prior autologous transplant. Overall survival was 46% (95% CI of 36-54%) at 1 year and 26% (95% CI 17-34%) at five years; the cumulative incidence of NRM at one year was 33% (95% CI 25-47%). A high Karnofsky performance status (KPS) (≥80%) was the strongest factor associated with a lower non-relapse mortality (NRM) (HR=0.47, p=0.03).  Age, stage of the disease, B-symptoms, CD34 dose, stem cell source, human leukocyte antigen (HLA) matching, and conditioning regimen were not significantly associated with NRM. The cumulative incidence of relapse was 44% (95% CI 35-55%) at one year and 53% (95%CI 42-66%) at five years. The cumulative incidence of relapse in patients without chronic graft-versus-host disease (cGVHD) was substantially higher than in patients with cGVHD (80% vs. 41%, HR=2.2, p=0.1). Relapse accounted for 47% (n=41) of the deaths, and the rest (n=46, 53%) were due to non-relapse causes. Of these, 39% (n=18) were due to GVHD-related causes.

Conclusions: Allogeneic HSCT is a treatment option for advanced, high risk DLBCL, particularly for patients with a good performance status, where overall survival is significantly better. Although all-cause mortality and disease recurrence continue to be high, 26% of the patients are long-term survivors. In this cohort, cGVHD was associated with a lower relapse rate, underscoring the benefits and importance of the graft-versus-lymphoma effect.

CI of OS According to KPS

KPS<80 KPS≥80