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Journal Article Review Epublish 9 citations

PubMed: 35683547 DOI: 10.3390/jcm11113160

Clonal Hematopoiesis and the Risk of Hematologic Malignancies after Curative Therapies for Sickle Cell Disease.

J Clin Med 11(11)

Authors: Lukasz P Gondek, Vivien A Sheehan, Courtney D Fitzhugh

Affiliations

  • Department of Oncology, Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, CRB1-290, 1650 Orleans Street, Baltimore, MD 21287, USA.
  • Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA 30322, USA.
  • Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institute, NIH, 10 Center Drive, Bethesda, MD 20814, USA.

Abstract

Sickle cell disease (SCD) is associated with severe morbidity and early mortality. Two large population studies found an increased risk for leukemia in individuals with SCD. Notably, while the relative risk of leukemia development is high, the absolute risk is low in individuals with SCD who do not receive cell-based therapies. However, the risk of leukemia in SCD is high after graft rejection and with gene therapy. Clonal hematopoiesis (CH) is a well-recognized premalignant condition in the general population and in patients after high-dose myelotoxic therapies. Recent studies suggest that CH may be more common in SCD than in the general population, outside the cell-based therapy setting. Here, we review risk factors for CH and progression to leukemia in SCD. We surmise why patients with SCD are at an increased risk for CH and why leukemia incidence is unexpectedly high after graft rejection and gene therapy for SCD. Currently, we are unable to reliably assess genetic risk factors for leukemia development after curative therapies for SCD. Given our current knowledge, we recommend counseling patients about leukemia risk and discussing the importance of an individualized benefit/risk assessment that incorporates leukemia risk in patients undergoing curative therapies for SCD.

MeSH

Graft Rejection, Cells, Genes, Hematopoiesis, Anemia, Sickle Cell, Hematologic Neoplasms, Clonal Hematopoiesis, Leukemia, Risk Factors, Transplants, Therapeutics

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