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Sequential treatment combining cladribine-based re-induction, myeloablative allogeneic HSCT, and prophylactic donor lymphocyte infusion: a promising treatment for refractory acute myeloid leukemia

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Abstract

We describe the first multicenter prospective study to assess the efficacy, safety, and immune reconstitution of a novel sequential transplant approach in 24 patients with primary induction failure/relapsed acute myeloid leukemia (AML). The sequential regimen consisted of cladribine 5 mg/m2/day and cytarabine 2 g/m2/day for 5 days and mitoxantrone 7 mg/m2/day for 3 days, followed by myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) using intravenous busulfan (3.2 mg/kg/day) for 4 days and cyclophosphamide (60 mg/kg/day) for 2 days. Patients in CR without acute graft-versus-host disease at day + 90 received prophylactic donor lymphocyte infusion (pDLI). At the time of transplantation, a marrow blast infiltration > 20% or any level of circulating blasts was found in 62.5% of patients. The cumulative incidence of relapse at 2 years was 29.8%. Overall survival (OS) was 74.5% at 1 year and 56.5% at 2 years. Leukemia-free survival (LFS) at 1 and 2 years was 62.5 and 50.5%, respectively. Multivariate analysis demonstrated that haploidentical related donor, pDLI, and experiencing chronic graft-versus-host disease (cGVHD) were protective from relapse. Total T cells and T cell subsets in peripheral blood recovered at 3 months post-HSCT. The expressions of immune checkpoints (cytotoxic T lymphocyte antigen 4 and programmed death 1) were extremely low in T cells over the first 1 year post-transplantation.

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Acknowledgements

We thank all transplant center physicians who participated in the study.

Funding

This work was funded in part by the National Natural Science Foundation of China (81470309).

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Authors and Affiliations

  1. Department of Hematology, Guangzhou General Hospital of Guangzhou Military Command, No. 111 Liuhua Rd., Guangzhou, 510010, Guangdong Province, People’s Republic of China

    Haowen Xiao, Yan Pang, Zujun Jiang, Zenghui Liu & Yang Xiao

  2. Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China

    Haowen Xiao & Hang Zhang

  3. Center of Cell-Biological Therapy and Research, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong Province, People’s Republic of China

    Li Li & Jiulong Wu

  4. Department of Hematology, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, People’s Republic of China

    Yuanbin Wu

  5. Department of Hematology, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China

    Fen Huang & Qifa Liu

  6. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China

    Yi Luo & He Huang

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  1. Haowen Xiao
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  11. Hang Zhang
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  12. Yi Luo
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  13. He Huang
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Contributions

Conception and design: Haowen Xiao.

Collection, analysis, and interpretation of the data: Haowen Xiao, Li Li, Yuanbin Wu, Jiulong Wu, and Fen Huang.

Drafting the article: Haowen Xiao.

Provision of study materials or patients: Haowen Xiao, Li Li, Yan Pang, Yuanbin Wu, Zujun Jiang, Zenghui Liu, Jiulong Wu, Yang Xiao, Fen Huang, Qifa Liu, Hang Zhang, Yi Luo, and He Huang.

Obtaining of funding: Haowen Xiao.

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Correspondence to Haowen Xiao.

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Xiao, H., Li, L., Pang, Y. et al. Sequential treatment combining cladribine-based re-induction, myeloablative allogeneic HSCT, and prophylactic donor lymphocyte infusion: a promising treatment for refractory acute myeloid leukemia. Ann Hematol 97, 2479–2490 (2018). https://doi.org/10.1007/s00277-018-3453-z

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  • DOI: https://doi.org/10.1007/s00277-018-3453-z

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