Late Effects of Allogeneic Stem Cell Transplantation for Non-Hodgkin Lymphoma. Swiss Cohort Analysis 1997-2021

Abstract

Background: despite rapid development of new highly efficient targeted and cellular-therapies, allogeneic stem cell transplantation (allo-HSCT) represents so far the only potentially curable treatment according to a longest follow-up in a setting of relapse/refractory Non-Hodgkin lymphoma (rrNHL). However, late effect (LE) issues of allo-HSCT in rrNHL seem to be underexplored. Here, we present the first analysis of a retrospective, multicenter, registry-based analysis (Swiss Blood Stem Cell Transplantation and Cellular Therapy, SBST) of LE in patients who underwent allo-HSCT for rrNHL in Switzerland. Methods: We retrospectively collected data from 109 patients with all types of rrNHL who underwent allo-HSCT in 3 University Hospitals of Switzerland (Zurich, Basel and Geneva) between May 1997 and November 2021. The inclusion criteria was 2 years survival after allo-HSCT. The primary endpoint was the cumulative incidence (CI) of LE and secondary endpoint were overall survival (OS), relapse incidence (RI) and type of LE according to organ/systems involved. Results: median of follow-up was 6.5 years. Patients who survived 2 years after allo-HSCT presented 5 and 10 years OS of 94% [95% CI 86.3 - 97.5] and 86% [95% CI 75 - 92.4] respectively. RI and CI of LE were 18.3% and 44% at 5 years and 34.4% and 58% at 10 years post allo-HSCT. A total of 79/109 (72%) of patients experienced any type of LE during the follow-up period. Renal dysfunction (21%), secondary malignancies (18%), cardiovascular disease (18%), osteoporosis (18%) and thyroid dysfunction (17%) were the most frequently observed. CI of secondary malignancies was 6.1% and 20% at 5 and 10 years respectively. Conclusions: Our analysis of a mixed-type rrNHL cohort confirms the efficacy of allo-HSCT in heavily pretreated/refractory patients, showing excellent OS at 5 and 10 years for those who survived 2 years. Both RI and LE present a competitive risk for survival benefit beyond 2 years after allo-HSCT. Secondary malignancies, renal and cardiovascular disease appear to be the most frequent types of LE, revealing the toxicity accumulated prior to allo-HSCT in the setting of rrNHL. These results should be interpreted with caution due to a retrospective nature of the analysis, the heterogeneity of the conditioning regimen and the NHL cohort. Figure 1. a) Overall survival (KM-estimate) b) cumulative incidence of late effects