Clonal hematopoiesis in hematopoietic stem cell transplantation

Curr Opin Hematol. 2021 Mar 1;28(2):94-100. doi: 10.1097/MOH.0000000000000631.

Abstract

Purpose of review: Clonal hematopoiesis (CH) is characterized by the acquisition of somatic mutations and subsequent expansion of mutated hematopoietic stem and progenitor cell (HSPC) clones without clinical evidence for a hematologic neoplasm. The prevalence of CH continuously increases with age reaching double-digit percentages in individuals >60 years. CH is associated with an increased risk for hematologic neoplasms and cardiovascular disease. We will review recent efforts to investigate how CH influences patient outcomes in hematopoietic stem cell transplantation - both autologous (ASCT) and allogeneic (allo-HSCT).

Recent findings: Donor-engrafted CH is common in allo-HSCT recipients. Apart from a higher incidence of chronic GvHD and the rare but devastating complication of donor-derived leukemia, CH does not appear to negatively impact outcomes in allo-HSCT recipients. In lymphoma patients undergoing ASCT, however, CH is associated with an excess mortality driven by therapy-related myeloid neoplasms and cardiovascular events. Interestingly, inferior overall survival in patients with CH undergoing ASCT for multiple myeloma (MM) is due to an increased rate of MM progression.

Summary: CH is highly prevalent in both allo-HSCT and ASCT patients suggesting a clinically relevant but context-dependent impact on adverse outcomes. Given the current lack of therapeutic interventions, systematic screening for CH in the transplant setting is currently not indicated outside of clinical studies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Differentiation
  • Clonal Evolution / genetics
  • Clonal Hematopoiesis*
  • Disease Management
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / methods
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Outcome Assessment, Health Care
  • Prognosis
  • Tissue Donors
  • Transplantation, Autologous
  • Transplantation, Homologous