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Annals of Hematology

, Volume 97, Issue 12, pp 2479–2490 | Cite as

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

  • Haowen Xiao
  • Li Li
  • Yan Pang
  • Yuanbin Wu
  • Zujun Jiang
  • Zenghui Liu
  • Jiulong Wu
  • Yang Xiao
  • Fen Huang
  • Qifa Liu
  • Hang Zhang
  • Yi Luo
  • He Huang
Original Article

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.

Keywords

Refractory acute myeloid leukemia Cladribine Myeloablative allogeneic hematopoietic stem cell transplantation Prophylactic donor lymphocyte infusion Immune checkpoints 

Notes

Acknowledgements

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

Author 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.

Funding information

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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

277_2018_3453_MOESM1_ESM.docx (13 kb)
Supplementary Table 1 (DOCX 13 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of HematologyGuangzhou General Hospital of Guangzhou Military CommandGuangzhouPeople’s Republic of China
  2. 2.Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhouPeople’s Republic of China
  3. 3.Center of Cell-Biological Therapy and ResearchGuangzhou General Hospital of Guangzhou Military CommandGuangzhouPeople’s Republic of China
  4. 4.Department of HematologySecond Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhouPeople’s Republic of China
  5. 5.Department of HematologyNanfang Hospital of Southern Medical UniversityGuangzhouPeople’s Republic of China
  6. 6.Bone Marrow Transplantation Center, The First Affiliated HospitalZhejiang University School of MedicineHangzhouPeople’s Republic of China

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