Allogeneic Stem Cell Transplantation for Patients with Chemo-Refractory or Progressive Aggressive Non-Hodgkin's Lymphomas.

Abstract

Background: Patients (pts) with chemo-refractory (Cref) and/or progressive aggressive non-Hodgkin's lymphomas (A-NHL) generally have a poor clinical outcome. Autologous stem cell transplantation (SCT) has limited efficacy in this setting. Studies reporting outcomes of allogeneic (Allo) SCT in pts with Cref A-NHL are limited.Methods: 108 pts with A-NHL underwent Allo-SCT between 1988 and 2007 at our institution. 46 A-NHL pts with Cref (i.e pts with <50% reduction in tumor size and/or persistent bone marrow involvement following chemotherapy) or progressive disease (PD) by CT-criteria were eligible for this analysis. Positron emission tomography (PET) or PET/CT scans were not performed to assess response.Results: The median age was 46 years (range 22–63 yrs). 39 pts received matched sibling allografts, while 7 underwent unrelated donor SCT. All except 3 pts received myeloablative conditioning. 38 pts received BU/CY-based conditioning, while BEAM (n=5) or Flu/Bu (n=3) was employed in the remaining pts. Diagnosis included diffuse large B-cell lymphoma (n=18), Burkitt's lymphoma (n=3), transformed lymphoma (n=5), mantle cell lymphoma (n=11) and T-cell lymphomas (n=9). The median number of prior therapies was 3 (range 1–8). 32 pts had Cref disease, while 14 had PD. 41 pts had stage III/IV disease, 23 had elevated LDH, while 36 had extranodal involvement. Median follow-up of surviving pts following Allo-SCT is 5-yrs. The 5-yr overall survival (OS), progression free survival (PFS), and relapse rate for the whole cohort (n=46) was 38%, 34%, and 35% respectively. Rate of grade II-IV acute graft-versus-host disease (GVHD) was 43% (n=20). Among the 33 evaluable pts rate of chronic GVHD was 75%. Overall non-relapse mortality rate was 37%. No significant difference in the baseline characteristics of pts with Cref and PD was present. The 5-yr OS and PFS rates for pts with Cref and PD were 46% vs. 21% (p-value=0.01; log-rank test), and 46% vs. 7% (p-value=0.0002; log-rank test) respectively. On multivariate analysis only PD at the time of SCT predicted for worse OS and PFS.Conclusion: Our study shows encouraging efficacy of Allo-SCT in a group of A-NHL pts with Cref disease by CT scan-criteria who often fail following Auto-SCT. However outcomes of pts with PD remain dismal despite Allo-SCT, and our data question the practice to perform allografting in A-NHL pts with PD. We hypothesize that PET scans may help better define patients with aggressive NHL appearing not to have responded to salvage chemotherapy by standard CT criteria that still may derive significant benefit from allografting.