Circulating CD117+/CD34+/CD45dim Myeloblasts as Biomarkers of Disease Activity in Primary Myelofibrosis-A Pilot Study

Clinical benefit measures and surrogates for leukaemic transformation or overall survival are scarce in MF. Circulating myeloblast (CMB) counts have the biological plausibility to indicate disease evolution, but they are still determined by an outdated approach with microscopic examination and fixed cut-offs. Our aim was to evaluate the prognostic value of CD117+/CD34+/CD45dim CMBs (CMB-FC) as continuous variables in MF patients at diagnosis and during cytoreductive therapy.

Absolute counts (CMB-FC#) and relative percentages (CMB-FC%) were determined using multiparameter flow cytometry (FC). Associations of CMB-FCs and well-established prognostic markers of MF were determined by linear regression and non-parametric tests. Longitudinal CMB-FC changes were analysed using linear mixed-effects models.

In the 29 analysed patients, meaningful correlations were observed between CMB-FCs and blood counts, JAK2 VAF and LDH levels among several other markers. Patients with overt MF had higher CMB-FC# and CMB-FC% compared to those with a pre-fibrotic histological subtype, while CMB-FC# increased gradually with fibrosis grade and within well-established prognostic scores. No significant effect on CMB-FC levels was observed over time in response to treatment.

This novel approach for quantifying CMBs has strong potential to reflect disease activity and prognosis in MF.

Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.