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Characteristics and prognosis of central nervous system relapse after allogeneic hematopoietic stem cell transplantation in adult patients with leukemia

Bone Marrow Transplantation (2025)Cite this article

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Abstract

Central nervous system(CNS) is a common site of extramedullary involvement after allogeneic hematopoietic stem cell transplantation(allo-HSCT). It may confer inferior survival when combined with bone marrow(BM) relapse in leukemia patients. We performed a retrospective study to investigate the associated risk factors and prognosis in adult patients with post-transplant CNS relapse. Between 2016 and 2024 in our center, 74 leukemia patients developed CNS relapse after allo-HSCT, with 23 cases of isolated CNS(iCNS) relapse and 51 cases of combined CNS and BM(CNS&BM) relapse. Patients with CNS&BM relapse after allo-HSCT conferred inferior 5-year overall survival (OS) compared with those with iCNS relapse, and independent risk factors related with CNS&BM relapse were identified, including male gender(relative risk ratio[RR] = 4.09, 95% confidence interval [CI] = 1.29–13.02, p = 0.017), HLA-identical transplantation (RR = 4.11, 95% CI = 1.10–15.32, p = 0.035), and without chronic graft-versus-host disease occurrence (RR = 3.73, 95% CI = 1.00–13.84, p = 0.049). Early CNS relapse was identified as an independent predictor of worse 5-year OS from HSCT for patients with CNS&BM relapse (n = 51, <12 months after allo-HSCT, hazard ratio=7.35, p = 0.003). Systemic therapy after CNS relapse reduced subsequent BM relapse for ALL and CML patients (p = 0.038). These findings demonstrate the outcome of patients with post-transplant CNS&BM relapse remains very poor. HLA-haploindentical allo-HSCT and systemic therapy after CNS relapse may better reduce BM relapse.

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Fig. 1: Impact of underlying disease on CNS relapse timing following allo-HSCT.
Fig. 2: The profile of molecular genetic alteration in leukemia patients with CNS relapse after allo-HSCT.
Fig. 3: Overall survival from the date of post-transplant CNS relapse, stratified by diagnosis, relapse sites and treatment.
Fig. 4: Treatment patterns and outcomes in patients with post-transplant CNS relapse but before BM relapse.

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Data availability

The data supporting the findings are not publicly available due to privacy or ethical restrictions. The data are available upon reasonable request from the corresponding author.

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Funding

This work was partly supported by the National Key Research and Development Program of China (No. 2023YFC2508905), the National Natural Science Foundation of China (82470214 & 82270227 & 82200240), Major Program of the National Natural Science Foundation of China (No. 82293630), Beijing Municipal Science & Technology Commission (No. Z211100002921071), Peking University Medicine Fund for world’s leading discipline or discipline cluster development (No.71003Y3035).

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Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China

    Li-ping Guo, Li-juan Hu, Xiao-dong Mo, Yu-qian Sun, Yi-fei Cheng, Lan-ping Xu, Xiao-hui Zhang, Xiao-Jun Huang & Yu Wang

  2. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China

    Xiao-Jun Huang

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Contributions

YW and XJH conceived, designed the study. YW supervised the manuscript preparation. LPG collected patient data with the help of LJH, XDM, YQS, YFC, LPX, XHZ. LPG performed data analysis and wrote the manuscript under supervision of YW. All authors read and approved the final manuscript.

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Correspondence to Yu Wang.

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Guo, Lp., Hu, Lj., Mo, Xd. et al. Characteristics and prognosis of central nervous system relapse after allogeneic hematopoietic stem cell transplantation in adult patients with leukemia. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02673-4

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