非霍奇金淋巴瘤患者异基因干细胞移植的晚期毒性：基于 SBST 的分析 1997-2021 及文献综述

Allogeneic stem cell transplantation (allo-HSCT) represents the sole potentially curative treatment according to the longest follow-up for relapsed/refractory non-Hodgkin lymphoma NHL (rrNHL).

Given the improvement in 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 chimeric antigen receptor T cell (CAR-T) therapy, 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; LEs) is highly warranted.

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.

We retrospectively analyzed data from 97 patients, identified in the 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) 2-year survival after first allo-HSCT. The exclusion criteria were (1) allo- or auto-HSCT performed primarily for diseases other than NHL and (2) death from any cause within 2 years after allo-HSCT or loss to follow-up.

The primary endpoint was cumulative incidence of LE; secondary endpoints were overall survival (OS), relapse incidence (RI), type of LE by involved organ systems, and risk factors for LE development. The median duration of follow-up was 8 years. The mean age of patients at the time of allo-HSCT was 46 years. The mean time to relapse was 1. 9 years.

The cumulative incidence of LE was 33% at 5 years and 50% at 10 years. The mean time for development of LEs was 2. 6 years. The most frequent LEs were chronic kidney failure (22%), cardiovascular disease (20%), osteoporosis (18%), and thyroid dysfunction (13%). The cumulative incidence of secondary malignancies was 6. 1% at 5 years and 20% at 10 years.

Our analysis of a mixed-type rrNHL cohort confirms the efficacy of allo-HSCT in heavily pretreated/refractory patients, showing excellent OS (Figure 1) at both 5 years and 10 years for those who survived 2 years. Secondary malignancies, renal, bone, and cardiovascular disease appear to be the most frequent types of LEs, 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 antibody therapies.