Effect of allogeneic HCT from unrelated donors in AML patients with intermediate- or poor-risk cytogenetics: a retrospective study from the Japanese Society for HCT

Abstract

This study aimed to analyze the factors associated with outcomes of bone marrow transplantation (UR-BMT) or cord blood stem cell transplantation from unrelated donors (UR-CBT). We assessed the time from diagnosis to transplantation among acute myeloid leukemia (AML) patients with intermediate- or poor-risk cytogenetics to identify the potential clinical efficacy of transplantation. We retrospectively analyzed 5331 patients who received UR-BMT or UR-CBT between 2008 and 2017. Patients were divided into four groups according to time from diagnosis to transplantation: (1) UR-BMT and > 5 months (n = 2353), (2) UR-BMT and ≤ 5 months (n = 379), (3) UR-CBT and > 5 months (n = 1494), and (4) UR-CBT and ≤ 5 months (n = 1106). There was no difference in overall survival (OS) for transplantation at ≤5 months and > 5 months in patients with first complete remission for both UR-BMT and UR-CBT, but OS in patients with primary induction failure (PIF) and transplantation at ≤ 5 months was significantly higher in the UR-CBT group compared with that at >5 months (P < 0.001). Multivariate Cox regression analysis also showed that transplantation at >5 months in patients with PIF was an independent predictor of poorer OS. Therefore, UR-CBT at ≤ 5 months after diagnosis is an alternative option for AML patients with PIF.

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Acknowledgments

We thank the patients and clinical staff for their participation in this study. We are grateful to the Japanese Data Center for Hematopoietic Cell Transplantation for data management, and to the Clinical Research Institute of Kyushu Medical Hospital for their editorial support. We thank H. Nikki March, PhD, from Edanz Group (https://en-author-services.edanzgroup.com/) for editing a draft of this manuscript.

Funding

This study was supported by The Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) of the Japan Agency for Medical Research and Development (AMED).

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Authors

Contributions

S.Y. contributed to the study design, data analysis, and manuscript preparation; J.M., J.K., N.I., Y.K., Y.A., M.Y., and S.Y. contributed to the manuscript preparation; N.U., N.D., M.T., T.K., T.E., Y.O., S.T., and M.O. provided the clinical data; M.H, Y.K., Y.K., and Y.A. managed the clinical data; and all authors reviewed the manuscript.

Corresponding author

Correspondence to Satoshi Yamasaki.

Ethics declarations

This study was approved by the data management committee of the Japanese Society for Hematopoietic Cell Transplantation and the institutional review board of Kyushu Medical Center.

Conflict of interest

The authors declare that there are no competing financial interests regarding this article.

Informed consent

The Transplant Registry Unified Management Program database included physician-reviewed data. Observational studies based on the Transplant Registry Unified Management Program databases were performed with informed consent.

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Supplemental Fig 1

Box plot of time from diagnosis to UR-BMT (A) and UR-CBT (B) by disease status at HCT. Within each box, horizontal black lines denote median values; boxes extend from the 25th to the 75th percentile of each group’s distribution of values; vertical extending lines denote adjacent values; dots denote observations outside the range of adjacent values. HCT, hematopoietic cell transplantation; UR-BMT, bone marrow transplantation from an unrelated donor; UR-CBT, cord blood transplantation from an unrelated donor; CR, complete remission at HCT; CR1, first CR; CR2, second CR; CR > 2, third or greater CR; 1Rel, first relapse; 2Rel, second relapse; >2Rel, third or greater relapse; PIF, primary induction failure. (PPTX 78 kb)

Supplemental Fig 2–4

Cumulative incidence of neutrophil engraftment (Supplemental Fig. 1) and acute (Supplemental Fig. 2) and chronic (Supplemental Fig. 3) GVHD in four groups of patients who received UR-BMT or UR-CBT for intermediate- or poor-risk AML: UR-BMT at >5 months, UR-BMT at <5 months, UR-CBT at >5 months, and UR-CBT at <5 months. (PPTX 135 kb)

Supplemental Fig 5

Cumulative incidence of TRM (A) and relapse (B), and Kaplan–Meier estimates of DFS (C), current GRFS (D), refined GRFS (E), and OS (F) in four groups of AML patients with intermediate- or poor-risk cytogenetics who received UR-BMT or UR-CBT: UR-BMT at >5 months, UR-BMT at <5 months, UR-CBT at >5 months, and UR-CBT at <5 months. TRM, transplant-related mortality DFS, disease-free survival; GVHD, graft-versus-host disease; cGRFS, current GVHD-free, relapse-free survival; rGRFS, refined GRFS; OS, overall survival; UR-BMT, bone marrow transplantation from an unrelated donor; UR-CBT, cord blood transplantation from an unrelated donor; AML, acute myeloid leukemia; HCT, hematopoietic cell transplantation. (PPTX 228 kb)

Supplemental Fig] 6.

Cumulative incidence of TRM (A) and relapse (B), and Kaplan–Meier estimates of DFS (C), current GRFS (D), refined GRFS (E), and OS (F) in AML patients with intermediate- or poor-risk cytogenetics and CR1 who underwent UR-BMT or UR-CBT. According to the time from diagnosis to HCT, we divided patients into four groups: UR-BMT at >5 months, UR-BMT at <5 months, UR-CBT at >5 months, and UR-CBT at <5 months. TRM, transplant-related mortality; DFS, disease-free survival; GVHD, graft-versus-host disease; cGRFS, current GVHD-free, relapse-free survival; rGRFS, refined GRFS; OS, overall survival; UR-BMT, bone marrow transplantation from an unrelated donor; UR-CBT, cord blood transplantation from an unrelated donor; AML, acute myeloid leukemia; CR1, first complete remission; HCT, hematopoietic cell transplantation. (DOCX 29 kb)

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Yamasaki, S., Mori, J., Kanda, J. et al. Effect of allogeneic HCT from unrelated donors in AML patients with intermediate- or poor-risk cytogenetics: a retrospective study from the Japanese Society for HCT. Ann Hematol (2020). https://doi.org/10.1007/s00277-020-04261-6

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Keywords

  • Acute myeloid leukemia
  • Bone marrow transplantation
  • Cord blood stem cell transplantation
  • Unrelated donors