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Allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first complete remission after 5-azacitidine and venetoclax: a multicenter retrospective study

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Abstract

The combination of hypomethylating agents and venetoclax has revolutionized the therapeutic landscape of acute myeloid leukemia (AML), especially for patients previously deemed unfit for curative–intent treatment. Some of these patients undergo allogeneic hematopoietic cell transplant (alloHCT); yet, there are scarce data regarding transplantation outcomes. We conducted a multicenter nationwide retrospective cohort study, including patients with AML who underwent alloHCT in CR1 after frontline treatment with azacitidine plus venetoclax only (aza-ven group). We collected a historical control group of patients who achieved CR1 after first-line intensive chemotherapy only, followed by alloHCT (intensive group). Patients in the aza-ven group (n = 24) were transplanted between 2019 and 2021. Compared to the intensive group, patients in the aza-ven group were older (median age 71.7 vs. 58.4 years), had higher incidence of therapy-related AML and AML with antecedent hematologic disorder and had more often adverse cytogenetics. They had a higher percentage of allografts from matched-unrelated donors, and reduced intensity conditioning was more commonly used. The estimated 12 months non relapse mortality was 19.1% in the aza-ven group and 11.8% in the intensive group. The estimated 12 months relapse-free survival and overall survival were 58% and 63% in the aza-ven group and 54% and 70% in the intensive group, respectively. The cumulative incidence of acute GVHD at 6 months and of chronic GVHD at 12 months were 58% and 40% in the aza-ven group and 62% and 42% in the intensive group, respectively. Analysis of the aza-ven group revealed that HCT-CI score and ELN risk category were predictive of RFS in both univariate analysis as well as multivariate analysis. Our data suggests that alloHCT for AML patients achieving first CR with aza-ven appears feasible, with short-term post-transplant outcomes similar to those expected after traditional intensive chemotherapy.

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Author notes

  1. Oren Pasvolsky and Shai Shimony these authors contributed equally

Authors and Affiliations

  1. Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah-Tikva, 39 Ze’ev Jabotinsky Rd, 49100, Petah-Tikva, Israel

    Oren Pasvolsky, Shai Shimony, Liat Shargian, Ofir Wolach, Pia Raanani & Moshe Yeshurun

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Oren Pasvolsky, Shai Shimony, Ron Ram, Avichai Shimoni, Liat Shargian, Ofir Wolach, Ronit Yerushalmi, Odelia Amit, Pia Raanani & Moshe Yeshurun

  3. Bone Marrow Transplantation Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

    Ron Ram & Odelia Amit

  4. Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel

    Avichai Shimoni & Ronit Yerushalmi

  5. Institute of Hematology, Hadassah Medical Center and Hebrew University, Jerusalem, Israel

    Batia Avni

  6. Statistical Consultant, Rabin Medical Center, Petach Tikva, Israel

    Tzippy Shochat

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  1. Oren Pasvolsky
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Contributions

OP contributed to research design, acquisition of data, analysis and interpretation of data, drafted the manuscript and approved the submitted and final versions; SS contributed to research design, acquisition of data, analysis and interpretation of data, drafted the manuscript and approved the submitted and final versions; RR contributed to research design, acquisition of data, revised the manuscript critically and approved the submitted and final versions; AS contributed to research design, acquisition of data, revised the manuscript critically and approved the submitted and final versions; LS contributed to the acquisition of data, revised the manuscript critically and approved the submitted and final versions; BA contributed to the acquisition of data, revised the manuscript critically and approved the submitted and final versions; OW contributed to research design, analysis and interpretation of data, revised the manuscript critically and approved the submitted and final versions; TS contributed to research design, analysis and interpretation of data, revised the manuscript critically and approved the submitted and final versions; RY contributed to the acquisition of data, revised the manuscript critically and approved the submitted and final versions; OA contributed to the acquisition of data, revised the manuscript critically and approved the submitted and final versions; PR contributed to research design, analysis and interpretation of data, revised the manuscript critically and approved the submitted and final versions; MY contributed to research design, analysis and interpretation of data, drafted the manuscript and approved the submitted and final versions;

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

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Pasvolsky, O., Shimony, S., Ram, R. et al. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first complete remission after 5-azacitidine and venetoclax: a multicenter retrospective study. Ann Hematol 101, 379–387 (2022). https://doi.org/10.1007/s00277-021-04693-8

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