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Clonal hematopoiesis in patients with stem cell mobilization failure: a nested case-control study.

Carin L E Hazenberg1, Aniek O de Graaf2, René Mulder3

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Clonal hematopoiesis (CH) is common during stem cell mobilization for transplantation. While CH itself doesn't predict mobilization failure, specific mutations like TP53 and PPM1D are linked to poor outcomes and therapy-related myeloid neoplasms.

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Area of Science:

  • Hematology
  • Oncology
  • Genetics

Background:

  • Inadequate mobilization of peripheral blood progenitor cells (PBPCs) hinders autologous hematopoietic cell transplantation (auto-HCT).
  • Clonal hematopoiesis (CH), the presence of somatic mutations in hematopoietic cells, is increasingly recognized but its impact on PBPC mobilization is unclear.

Purpose of the Study:

  • To investigate the association between CH and PBPC mobilization failure in patients undergoing auto-HCT.
  • To identify specific genetic mutations within CH that correlate with poor mobilization potential.

Main Methods:

  • A cohort of 776 patients undergoing auto-HCT was analyzed.
  • A nested case-control study involving 90 poor mobilizers and 89 controls used targeted next-generation sequencing of 28 genes.
  • CH was defined as mutations with variant allele frequency (VAF) ≥ 1%.

Main Results:

  • CH was detected in 27% of patients and did not significantly associate with poor mobilization (OR, 1.55; P=.238).
  • PPM1D mutations were more frequent in poor mobilizers (P=.005), and TP53 mutations exclusively occurred in this group (P=.06).
  • Patients with mobilization failure had a higher incidence of therapy-related myeloid neoplasms (t-MN) and worse overall survival, independent of CH presence.

Conclusions:

  • CH is prevalent during stem cell mobilization, particularly at low VAF (1%-10%).
  • TP53 and PPM1D mutations are associated with poor PBPC mobilization potential.
  • Further research is needed to establish the role of these mutations in the development of t-MN in patients with mobilization failure.