Late toxicity of allogeneic stem cell transplantation for Non-Hodgkin lymphoma patients. SBST based analysis 1997-2021 and review of literature.

Background allogeneic stem cell transplantation (allo-HSCT) represents so far the only potentially curable treatment according to a longest follow in a setting of relapse/refractory NHL (rrNHL). Given the improvement of NRM rates, the number of allo-HSCT survivors for rrNHL is continuously increasing. However, given the emergence of new, less toxic cell therapies, such as CAR-T, the role of allo-HSCT and the optimal timing of its use in the treatment of rrNHL need to be redefined. To this end, an analysis of late toxicity (late effects, LE) is highly warranted. Objective We present here the first retrospective, multicentre, registry-based analysis (Swiss Blood Stem Cell Transplantation and Cellular Therapy, SBST) of LE in patients, who underwent allo-HSCT for rrNHL in Switzerland. Study Design We retrospectively analyzed data from 97 patients, identified in the Swiss Blood Stem Cell Transplantation and Cellular Therapy (SBST) 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 were 1) diagnosis of any type of NHL and 2) two years survival after 1st allo-HSCT. The exclusion criteria were 1) allo- or auto-HSCT performed primarily for other disease than NHL 2) patient's death of any cause within 2 years post- allo-HSCT or loss of follow up. The primary endpoint was cumulative incidence (CI) of LE; secondary endpoints were overall survival (OS), RI, type of LE by involved organ systems, and risk factors for their development. Results Median of follow-up was 8 years. The mean age of patients at the time of allo-HSCT was 46 years. Mean time to relapse was 1.9 years. CI of LE was 33% and 50% at 5 and 10 years. Mean time for LE was 2.6 years. Most frequent were chronic kidney failure (22%), cardiovascular disease (20%), osteoporosis (18%), and thyroid dysfunction (13%). CI of secondary malignancies was 6.1% and 20% at 5 and 10 years (Fig. 2). Conclusions Our analysis of a mixed-type rrNHL cohort confirms the efficacy of allo-HSCT in heavily pretreated/refractory patients, showing excellent OS (Fig. 1) at 5 and 10 years for those who survived 2 years. Secondary malignancies, renal, bone and cardiovascular disease appear to be the most frequent types of LE, revealing accumulated toxicity in heavily pretreated patients with rrNHL. Our findings suggest that allo-HSCT remains a potentially curative option with manageable late toxicity for patients with rrNHL, even in the current era of novel cellular therapies. However, its place and timing of application in the treatment algorithm for rrNHL should be further evaluated with extended survival follow up with CAR-T and bispecific antibodies therapies.