Long-Term Follow-up of Sequential Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Acute Lymphoblastic Leukemia Patients Achieving MRD-Negative CR after CAR-T Therapy
Authors: Yang Tingting , Dong Yetian , Shi Jimin , Zhang Mingming , Feng Jingjing , Fu Shan , Xiao Pingnan , Hong Ruimin , Xu Huijun , Luo Yi , Zhao Yanmin , Yu Jian , Lai Xiaoyu , Fu Huarui , Ye Yishan , Cui Jiazhen , Huang Simao , Wei Guoqing , Chang Alex H. , Huang He , Hu Yongxian 
Published: December 2024

Background: In patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), maintenance therapy following chimeric antigen receptor T-cell (CAR-T) therapy is crucial for consolidating CAR-T efficacy and preventing relapse.However, the role of bridging allogeneic hematopoietic stem cell transplantation (HSCT) remains controversial due to serious transplant-associated complications. In our previous study, we discussed the short-term outcomes of bridging HSCT after CAR-T therapy. Here, we extend our findings by reporting the long-term outcomes of these patients, providing further insights into the efficacy and safety of this sequential treatment approach.

Methods: We conducted a retrospective analysis of patients with relapsed/refractory ALL who achieved MRD-negative (MRD-) CR following CAR-T therapy and subsequently underwent HSCT from January 2016 to May 2024. Clinical outcomes, including overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM), cumulative incidence of relapse (CIR) and graft-versus-host disease (GVHD) were assessed over a median follow-up period of 42 months (range, 4.0-99.0) after transplant.The follow-up data cutoff date was July 31, 2024.

Results: A total of 51 patients were enrolled in the study, with a median age at transplant of 32.1 years (range, 14.6-67.1). Twenty-one (41.2%) patients were classified as poor risk according to NCCN 2021, and 10 (19.6%) had BCR/ABL-positive. The majority (88.2%) underwent haploidentical related transplants, and the remaining 11.8% received either unrelated matched or related matched HSCT. Neutrophil engraftment was observed in all participants at a median time of 13 days (range, 10-29). 96.0% achieved platelet engraftment with a median time of 15 days (range, 7-29), and 2 developed platelet failure. Acute GVHD (aGVHD) occurred in 31.4% of patients, with grade II aGVHD in 15.7%. The cumulative incidence of chronic GVHD at 4 years was 48.4%.

As of the data cut-off, 15 (29.4%) cases experienced relapse, predominantly antigen-positive relapse (n=11). The median interval from transplant to the first relapse was 5.0 months (range, 2.7 to 48.9). The OS, LFS, NRM and CIR at 4 years were 68.7% (95 CI%, 56.7 to 83.4%), 61.3% (95 CI%, 48.9- 76.7%), 10.6% and 28.1%, respectively. In multivariate analyses, older age at transplant (HR: 3.78, 95% CI: 1.25-11.37, p = 0.018; HR: 3.62, 95% CI: 1.46-8.97, p = 0.005) and poor risk (HR: 3.16, 95% CI: 1.07-9.32, p = 0.037; HR: 2.73, 95% CI: 1.11-6.73, p = 0.029) were significantly associated with inferior OS and LFS.

Conclusions: Our study highlights the potential long-term benefits of bridging allogeneic HSCT in MRD-CR after CAR-T therapy in patients with R/R B-ALL. The benefits are less pronounced in patients with older age or poor-risk disease characteristics.