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Ruxolitinib is an effective salvage treatment for multidrug-resistant graft-versus-host disease after haploidentical allogeneic hematopoietic stem cell transplantation without posttransplant cyclophosphamide

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Abstract

The purpose of our study is to identify the efficacy of ruxolitinib in human leukocyte antigen (HLA) haploidentical hematopoietic stem cell transplantation (haplo-HSCT) recipients with multidrug-resistant (MDR)-graft-versus-host disease (GVHD, n = 34). MDR-GVHD was defined as GVHD showing no improvement after at least 3 types of treatments. The median number of previous GVHD-therapies was 4 for both MDR-acute GVHD (aGVHD) and MDR-chronic GVHD (cGVHD). For MDR-aGVHD (n = 15), the median time to response was 10 days (range 2 to 65), and the overall response rate (ORR) was 60.0% (9/15), including 40.0% (6/15) complete response (CR) and 20.0% (3/15) partial response (PR). The 1-year probability of overall survival after ruxolitinib was 66.7%. The rates of hematologic and infectious toxicities were 73.3% and 46.7% after ruxolitinib treatment. For MDR-cGVHD (n = 19), the median time to response was 29 days (range 6 to 175), and the ORR was 89.5% (17/19), including 26.3% (5/19) CR and 63.2% (12/19) PR. All patients remained alive until our last follow-up. The rates of hematologic and infectious toxicities were 36.8% and 47.4% after ruxolitinib treatment. Ruxolitinib is an effective salvage treatment for MDR-GVHD in haplo-HSCT recipients.

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Funding

This work was supported by the Capital’s Funds for Health Improvement and Research (grant number 2018-4-4089), Peking University Medicine Fund of Fostering Young Scholars’ Scientific and Technological Innovation (grant number BMU2020PY007), National Key Research and Development Program of China (grant number 2017YFA0104500), the Key Program of the National Natural Science Foundation of China (grant number 81530046 and 81930004), the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (grant number 81621001), the Science and Technology Project of Guangdong Province of China (grant number 2016B030230003), Peking University Clinical Scientist Program (BMU2019LCKXJ003), National Science and Technology Major Project (grant number 2017ZX09304021), and the Fundamental Research Funds for the Central Universities.

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  1. Jiao-Yu Zhao and Si-Ning Liu contributed equally to this work.

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 Hematopoietic Stem Cell Transplantation, Beijing, China

    Jiao-Yu Zhao, Si-Ning Liu, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, Yu-Hong Chen, Kai-Yan Liu, Xiao-Jun Huang & Xiao-Dong Mo

  2. Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, 030001, China

    Jiao-Yu Zhao

  3. Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, Beijing, 2019RU029, China

    Lan-Ping Xu, Xiao-Jun Huang & Xiao-Dong Mo

  4. Peking-Tsinghua Center for Life Sciences, Beijing, 100044, China

    Xiao-Jun Huang

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Fig S1

Supplementary figure 1. Toxicities of ruxolitinib in the 5mg BID group and >5mg BID group: (A) hematologic toxicities of aGVHD (5mg BID: n=13, >5mg BID: n=2); (B)infectious toxicities of aGVHD; (C) hematologic toxicities of cGVHD (5mg BID: n=14, >5mg BID: n=25; (D) infectious toxicities of cGVHD (TIF 288 kb)

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Zhao, JY., Liu, SN., Xu, LP. et al. Ruxolitinib is an effective salvage treatment for multidrug-resistant graft-versus-host disease after haploidentical allogeneic hematopoietic stem cell transplantation without posttransplant cyclophosphamide. Ann Hematol 100, 169–180 (2021). https://doi.org/10.1007/s00277-020-04273-2

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