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Pattern of somatic mutation changes after allogeneic hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes

Bone Marrow Transplantation volume 57, pages 1615–1619 (2022)Cite this article

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Allogeneic hematopoietic cell transplantation (alloHCT) is an important part of the therapeutic algorithm of myeloid neoplasms. Risk of acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) relapse after alloHCT continues to be significant, and recent efforts have been devoted to dissecting the molecular pathways leading to posttransplant relapse [1]. The dynamic process of clonal evolution is shaped by the nature of ancestral hits and emergence of subclones to create a highly diverse clonal architecture [2, 3]. During the course of disease, both evolution drives and types of therapies mold the trajectory of this architectural change with extinction of less fit (more sensitive) subclones and appearance of new subclonal mutations as a result of a selection process [1]. However, if not eradicated by the therapy, ancestral mutations may remain present throughout the subsequent clinical course, alone or with other subclones, may initiate disease recurrence or be a source of persistent disease [3].

Previously, we investigated the impact of mutational landscapes in AML and MDS undergoing alloHCT [4]. In addition to molecular drivers, a limited normal hematopoietic stem cell compartment and allogenic immunogenicity play a fundamental role in determining the fate of the malignant process in the posttransplant setting. So far, studies comparing mutational landscape changes at post-alloHCT relapse to those at post-chemotherapy relapse are lacking. We theorized that the clonal selection process following alloHCT is distinct from that of post-chemotherapy relapse, as it is shaped not only by the exposure to the conditioning regimen, but also by graft-vs.-leukemia (GVL) responses. These factors may have implications for our understanding of the biology and timing of relapse, help to assign prognosis, and inform appropriate clinical management.

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Fig. 1: Pretransplant factors associated with relapse-free survival at 5 years after transplant.
Fig. 2: Relapse after allogeneic transplant.

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Data available on request from the authors.

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Authors and Affiliations

  1. Department of Hematology and Oncology, University Hospitals Cleveland Medical Center/ Case Western Reserve University, Cleveland, OH, USA

    Sanghee Hong

  2. Department of Quantitative Health Science, Lerner Resesarch Institute, Cleveland Clinic, Cleveland, OH, USA

    Lisa Rybicki

  3. Department of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OH, USA

    Carmelo Gurnari, Simona Pagliuca, Valeria Visconte & Jaroslaw P. Maciejewski

  4. Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy

    Carmelo Gurnari

  5. Department of Clinical Hematology, CHRU de Nancy, Nancy, France

    Simona Pagliuca

  6. Allogen Laboratories, Cleveland Clinic, Cleveland, OH, USA

    Aiwen Zhang & Dawn Thomas

  7. Department of Hematology and Oncology, National Institute of Health, Bethesda, MD, USA

    Jibran Durrani & Betty K. Hamilton

  8. Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

    Ronald M. Sobecks, Matt Kalaycio, Aaron T. Gerds, Hetty E. Carraway, Sudipto Mukherjee, Anjali S. Advani, Bhumika J. Patel & Jaroslaw P. Maciejewski

  9. Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA

    Mikkael A. Sekeres

  10. Sarah Cannon, Nashville, TN, USA

    Navneet S. Majhail

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  1. Sanghee Hong
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Contributions

SH and JPM wrote the paper and designed the research; SH and LR analyzed the data; VV, CG, and SP performed research and edited the paper; AZ, DT, and JD collected molecular data; RMS, CG, BKH, MK, ATG, HEC, SM, MAS, ASA, NSM, and BJP collected and analyzed clinical data; and JPM was the principal investigator.

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Correspondence to Jaroslaw P. Maciejewski.

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Hong, S., Rybicki, L., Gurnari, C. et al. Pattern of somatic mutation changes after allogeneic hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. Bone Marrow Transplant 57, 1615–1619 (2022). https://doi.org/10.1038/s41409-022-01762-y

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