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

Inadequate mobilization of peripheral blood progenitor cells (PBPC) is a limiting factor to proceed with autologous hematopoietic cell transplantation (auto-HCT). To assess the impact of clonal hematopoiesis (CH) on mobilization failure of PBPC for auto-HCT, we investigated the characteristics of poor mobilizers (with total PBPC collection <2x106 CD34+ cells/kg) in a consecutive single center cohort of 776 patients. Targeted error corrected next-generation sequencing of 28 genes was performed in a nested case-control cohort of 90 poor mobilizers and 89 matched controls. CH was detected in 48 out of 179 patients (27%), with most patients carrying a single mutation. The presence of CH (detected at VAF ≥1%) did not associate with poor mobilization potential (31% versus 22% in controls, OR 1.55, 95%CI 0.76-3.23, P=0.238). PPM1D mutations were detected more often in poor mobilizers (P=0.005). In addition, TP53 mutations in this cohort were detected exclusively in patients with poor mobilization potential (P=0.06). The incidence of therapy-related myeloid neoplasms (t-MN) was higher among patients with mobilization failure (P=0.014). Although poor mobilizers experienced worse overall survival (P=0.019), this was not affected by the presence of CH. We conclude that CH at low VAF (1-10%) is common at time of stem cell mobilization. TP53 mutations and PPM1D mutations associate with poor mobilization potential and their role in subsequent development of t-MN in these individuals should be established.