Abstract

Background:Diffuse Large B Cell Lymphoma (DLBCL) is the most common type of non‐Hodgkin lymphoma and, despite its aggressive course, it is potentially curable, particularly with R‐CHOP chemotherapy. However, for patients unresponsive or relapsing after such therapy the prognosis is worse, and salvage treatment with intensive chemotherapy followed by consolidation with Autologous Hematopoietic Cell Transplantation (AHCT) is the standard of care, based on the pivotal PARMA trial. However, this trial was developed in the pre‐Rituximab (R) era and the more recent CORAL trial shed new light on this issue and identified patients with early relapse following R‐based chemotherapy as having much worse outcomes, which was confirmed by subsequent trials.The Center for International Blood and Marrow Transplant Research evaluated the role of AHCT relative to the timing of treatment failure and noted that early rituximab failure had a higher risk of disease relapse in the 1st year after transplantation but beyond that timepoint no survival difference was observed.Aims:Our aim was to analyze the results of patients transplanted for relapsed or refractory DLBCL at our transplant center, when achieving first chemo‐sensitive remission (CR1p) following progressive disease after fist line chemotherapy or when achieving a second chemo‐sensitive remission because of relapse (CR2).Methods:We retrospectively collected data from patients submitted to AHCT at a single institution between 2007 and 2018, with a diagnosis of relapsed or refractory DLBCL and analyzed the outcomes in terms of time to relapse (TTR), progression‐free survival (PFS) and overall survival (OS).Results:We identified a total of 52 patients, with a median age of 43 years at diagnosis, and a median of two prior lines (1‐4) with R‐based chemotherapy. Before AHCT 32 patients were in CR1p and 20 were in CR2 and disease status was classified as complete remission (CR) in 38 patients, partial remission (PR) in 13 and 1 patient had stable.Following consolidation treatment with AHCT, 45 patients achieved CR, 5 patients were in PR and 2 presented progressive disease.With a median follow‐up time of 84 months, median OS was not reached for both patients in CR1p and CR2, however we can observe a trend towards better survival for patients in CR2. Time to relapse was significantly different between these groups, with patients transplanted in CR2 having higher median time to next relapse (91 vs 36 months, p = 0.01), however this difference was not transposed in terms of survival.Eleven patients died, seven of which because of progressive disease and the remaining four due to unrelated causes and in remission.Summary/Conclusion:Our results are in accordance with those from previous studies on this theme and, similarly, we cannot prove clear benefit of AHCT for primary refractory patients with DLBCL, despite the longer time to relapse observed in patients in CR2. It appears that lack of optimal response to first line chemotherapy has a negative impact on the duration of disease control post‐AHCT (despite the lack of influence in OS). Perhaps molecular and cytogenetic alterations may define subgroups of patients who may benefit the most from AHCT, which we did not evaluate because only the more recent diagnosis had such information available.It is evident, however, that new approaches for primary refractory patients with DLBCL are clearly needed.

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