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Mutation clonal burden and allogeneic hematopoietic cell transplantation outcomes in acute myeloid leukemia and myelodysplastic syndromes

Bone Marrow Transplantation volume 54, pages 1281–1286 (2019)Cite this article

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Abstract

Next generation sequencing (NGS) has become an important tool to inform disease risk for myeloid malignancies, however data remains conflicting regarding the significance of individual mutations. We performed targeted NGS on 112 patients with AML, and 80 with MDS, who underwent allogeneic hematopoietic cell transplantation. The most common mutations in AML were TET2 (14.7%), FLT3 (12.9%), DNMT3A (12.1%), and RUNX1 (7.8%). Complex cytogenetics (HR 2.82, P = .017) and disease status (<CR) (HR 2.58, P < .001) was significantly associated with worse RFS. No individual mutation, nor variant allelic frequency (VAF), was found to be prognostic, except mutations in the RNA-splicing pathway, (HR 2.09, P = .023). Within the MDS cohort, most common mutations were ASXL1 (12.5%), SRSF2 (12%), TET2 (8.8%), and TP53 (8.8%). Complex cytogenetics (HR 5.01, P < .001), and presence of U2AF1 (HR 3.60, P = .019), was associated with worse RFS. Analysis of VAF found that TP53 and EZH2 mutations with allelic frequencies of >33% were associated with poor RFS (HR 3.57, P = .017; and HR 6.57, P = .003; respectively). Molecular profiling is increasingly important in the care of patients with AML and MDS. Further studies are needed to understand the molecular complexities, including the significance of clonal burden, to better inform care decisions.

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Acknowledgements

This work was supposed by a Case Comprehensive Cancer Center Program Grant [JPM, NM, ML]

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Authors and Affiliations

  1. Blood and Marrow Transplant Program, Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA

    Betty K. Hamilton, Aaron T. Gerds, Matt Kalaycio, Ronald Sobecks & Navneet S. Majhail

  2. Quantitative Health Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA

    Lisa Rybicki

  3. Department of Translational Hematology and Oncologic Research, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA

    Casandra Hirsch, Bartlomiej Przychodzen & Jaroslaw Maciejewski

  4. Leukemia and Myeloid Disorders Cancer Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA

    Aziz Nazha, Aaron T. Gerds & Mikkael A. Sekeres

  5. Pediatric Blood and Marrow Transplant Program, Cleveland Clinic Children’s Hospital, Cleveland, OH, USA

    Rabi Hanna

  6. University Hospitals and Case Western Reserve University, Cleveland, OH, USA

    Marcos de Lima

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  1. Betty K. Hamilton
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  2. Lisa Rybicki
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Correspondence to Betty K. Hamilton.

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Hamilton, B.K., Rybicki, L., Hirsch, C. et al. Mutation clonal burden and allogeneic hematopoietic cell transplantation outcomes in acute myeloid leukemia and myelodysplastic syndromes. Bone Marrow Transplant 54, 1281–1286 (2019). https://doi.org/10.1038/s41409-019-0444-1

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