Sequential allogeneic HSCT after CAR-T therapy for relapsed/refractory acute lymphoblastic leukemia patients: A long-term follow-up result

Abstract

Introduction

CAR-T cell therapy has revolutionized the therapeutic landscape for relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), and bridging with allogeneic hematopoietic stem cell transplantation (allo-HSCT) has the potential to lower relapse rates. Nevertheless, the majority of existing studies have exclusively focused on short-term outcomes, resulting in a lack of comprehensive understanding of the long-term sustainability of overall prognosis.

Objectives

Our study aimed to provide real-world, long-term follow-up data for patients who underwent sequential therapy.

Methods

Patients with R/R B-ALL who achieved MRD^-CR following CAR-T therapy and subsequently underwent allo-HSCT between January 2016 and May 2024 were enrolled. The primary outcomes included overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM) and cumulative incidence of relapse (CIR). Acute and chronic graft-versus-host disease (GVHD) and graft-versus-host disease-free survival (GRFS) were also investigated.

Results

The median age at transplant of 32.1 years. Of these patients, 88.2 % underwent haploidentical-HSCT, and 11.8 % received either unrelated matched or related matched HSCT. The cumulative incidences of grades I-IV and grade II-IV aGVHD at day 100 were 31.4 % and 15.7 %, respectively. The cumulative incidence of cGVHD at 4 y ears was 48.3 %. With a median follow-up time of 43.2 months, OS, LFS, and GRFS at 4 years were 68.9 %, 61.4 %, and 39.5 %, respectively. Fifteen cases (29.4 %) experienced relapse, predominantly antigen-positive relapse (n = 11). NRM and CIR at 4 years were 10.6 % and 28.0 %, respectively. In the multivariate analyses, patients over 45 years of age and with poor-risk had significantly dismal OS (P = 0.018; P = 0.038) and LFS (P = 0.01; P = 0.03).

Conclusion

Our study exhibits favorable long-term outcomes consistent with those reported in clinical trials, with sustained, durable responses observed at the 4-year follow-up. However, these benefits are less pronounced in older patients and those with poor-risk disease characteristics.