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Low relapse risk in poor risk AML after conditioning with 10-day decitabine, fludarabine and 2 Gray TBI prior to allogeneic hematopoietic cell transplantation

Bone Marrow Transplantation volume 56, pages 1964–1970 (2021)Cite this article

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Abstract

Patients with poor risk acute myeloid leukemia (AML) have a dismal outcome. We hypothesized that combining decitabine with a standard non-myeloablative (NMA) conditioning regimen prior to allogeneic hematopoietic cell transplantation (allo HCT), might decrease the relapse incidence. We conducted a multicenter prospective phase II study (NCT02252107) with 10-day decitabine (20 mg/m2/day) integrated in a standard non-myeloablative conditioning regimen (3 days fludarabine 30 mg/m2 with 2 Gray total body irradiation (TBI)). Patients with AML ≥ 18 years in 1st (in)complete remission (CR/CRi) with a poor or very poor risk profile, as defined by the HOVON-132 protocol, were eligible. Results: Forty-six patients (median age 60; range 23–74) were included. Median follow up time was 44 months (range 31–65 months). The cumulative 1-year incidence of relapse and NRM were respectively 23% and 11%. Incidence of grade III-IV acute graft-vs-host-disease (GVHD) and severe chronic GVHD were 13% and 20%, respectively. One-year OS was 70%. Application of ELN 2017 risk classification to the study cohort revealed a cumulative one-year relapse rate of respectively 31% and 13% for the adverse and intermediate risk patients. To conclude, the 10-day DEC/FLU/TBI conditioning regimen prior to allo HCT in poor risk AML patients is effective and feasible.

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Fig. 1: The DEC/FLU/TBI regimen.
Fig. 2: Incidence of AML relapse during follow up.
Fig. 3: Overall survival (OS), relapse-free survival (RFS), and graft-vs-host-free and relapse-free survival (GRFS).

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Acknowledgements

This study was supported by an unrestricted grant from Jansen Cooperation and the Dutch Cancer Fund (KWF kankerbestrijding).

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  1. Marjan Cruijsen

    Present address: Catharina Hospital Eindhoven, Eindhoven, Netherlands

Authors and Affiliations

  1. Department of Hematology, Radboud University Medical Center Nijmegen, Nijmegen, the Netherlands

    Marjan Cruijsen, Walter J. F. M. van der Velden, Brigitte Bär, Nicolaas P. M. Schaap & Nicole N. M. Blijlevens

  2. Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

    Jacobien R. Hilberink, André B. Mulder, Marco R. de Groot, Edo Vellenga & Gerwin Huls

  3. Department of Laboratory Medicine, Radboud University Medical Center Nijmegen, Nijmegen, the Netherlands

    Joop H. Jansen

  4. Department for Health Evidence, Radboud University Medical Center Nijmegen, Nijmegen, the Netherlands

    Anton de Haan

  5. Department of Hematology, CHU and University of Liège, Liège, Belgium

    Frédéric Baron

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Correspondence to Marjan Cruijsen.

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GH joined advisory boards of Celgene and Jansen.

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Cruijsen, M., Hilberink, J.R., van der Velden, W.J.F.M. et al. Low relapse risk in poor risk AML after conditioning with 10-day decitabine, fludarabine and 2 Gray TBI prior to allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 56, 1964–1970 (2021). https://doi.org/10.1038/s41409-021-01272-3

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