Outcome of Lower-Intensity Allogeneic Transplantation in Non-Hodgkin Lymphoma after Autologous Transplantation Failure

Abstract

We studied the outcome of allogeneic transplantation after lower-intensity conditioning regimens (reduced-intensity [RIC] and non-myeloablative [NST]) in non-Hodgkin lymphoma (NHL) relapsing after autologous transplantation. Non-relapse mortality (NRM), lymphoma progression/relapse, progression-free survival (PFS) and overall survival (OS) were analyzed in 263 NHL patients. All had relapsed after a prior autologous transplant and then received allogeneic transplantation from related (n = 26) or unrelated donors (n= 237) after RIC (n = 128) or NST (n = 135), and were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) between 1996 and 2006. Median follow-up of survivors was 68 months (range, 3–111). Three-year NRM was 44% (95% CI, 37%–50%). Lymphoma progression/relapse at three years was 35% (95% CI, 29%–41%). Three-year probabilities of PFS and OS were 21% (95% CI, 16%–27%) and 32% (95% CI, 27%–38%) respectively. Superior performance score, longer interval between transplants, total-body irradiation-based conditioning regimen and lymphoma remission at transplantation correlated with improved PFS. Allogeneic transplantation after lower-intensity conditioning is associated with significant NRM, but can result in long-term PFS. We describe a quantitative risk model based on pretransplant risk factors in order to identify those likely to benefit from this approach.

A Phase II Study of a Nonmyeloablative Allogeneic Stem Cell Transplant with Peritransplant Rituximab in Patients with B Cell Lymphoid Malignancies: Favorably Durable Event-Free Survival in Chemosensitive Patients

“…For example, in a study with a similar fludarabine and cyclophosphamide conditioning backbone, >30% of chemosensitive patients with indolent lymphoma histologies relapsed after RIC allo-SCT (48). In our study, the addition of TBI at 200 cGy not only provides additional immune suppression with very low incidence of mixed-chimerism for a NMA regimen, but may actually contribute to a survival benefit as has been recently reported in a large registry study of RIC allo-SCT for NHL following ASCT failure (49). Lastly, B-cell depletion with rituximab may contribute to reduced TRM and potentially improved survival by its impact on chronic GVHD (50, 51).…”

Outcomes of autologous or allogeneic stem cell transplantation for non-Hodgkin lymphoma

“…Recently published, registry study showed 3 year probabilities of PFS and OS were 21% and 32%, respectively after RIC allo-SCT who had failed prior auto-SCT. 27 Despite the lower intensity of the conditioning regimens, 3 year NRM was high at 44%. This is in contrast to our series, albeit small numbers, we observed 0% 2 year NRM in patients receiving allo-SCT after failed auto-SCT.…”

Successful Treatment With Third Stem Cell Transplant From an Allogeneic Donor for a Patient With Relapsed Diffuse Large B-Cell Lymphoma

“…9 On the other hand, it was reported that the 3-year overall survival, disease-free survival, and treatment-related mortality after RIST were 32%, 21%, and 44% in 263 patients with malignant lymphoma who underwent RIST for recurrence after auto-SCT, and that poor prognostic factors included non-total body irradiation regimen, transplant in nonremission, and poor performance status at transplant. 10 In 101 patients with DLBCL who underwent allo-SCT (myeloablative conditioning regimen, n=37; RIST, n=64) for recurrence after auto-SCT, 3-year overall survival, progression-free survival, and treatment-related mortality were 54%, 42%, and 28% with no difference in outcome between pretransplant treatments. Poor prognostic factors included early relapse after auto-SCT, age 45 years or more, and transplant in nonremission.…”