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

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.