The immature platelet fraction in myelodysplastic syndromes: retrospective associations and exploratory prospective cohort assessment

The immature platelet fraction (IPF) reflects thrombopoiesis. We assessed the baseline IPF and outcomes in retrospective ( n = 364) and prospective ( n = 46; UMIN000057807) myelodysplastic syndrome cohorts. The primary endpoint was leukemia-free survival ([LFS]: acute myeloid leukemia transformation or death). Secondary endpoints were overall survival (OS) and hematological improvement with azacitidine. In the retrospective cohort, 50 LFS events occurred. An IPF > 6.8% was associated with shorter LFS and OS in unadjusted analyses (log-rank p = 0.033 and p = 0.022, respectively; univariable hazard ratio for LFS, 1.79; 95% confidence interval [CI], 1.02–3.16). After adjustment for age, platelet count, and the Revised International Prognostic Scoring System score, the association was similar in magnitude but not significant (adjusted hazard ratio, 2.02; 95% CI, 0.98–4.18; p = 0.057), and discrimination was modest (2-year time-dependent area under the curve, 0.638; 95% CI, 0.561–0.715). The continuous IPF was weakly correlated with the bone marrow megakaryocyte count (Spearman’s ρ = 0.50; p < 0.001), although median counts were identical across the IPF groups. In the prospective cohort, OS and LFS were not different between the IPF groups (patients with IPF ≤ 6.8% and > 6.8%; log-rank p = 0.929 and p = 0.402, respectively), with only three deaths and four LFS events. Among azacitidine-treated, response-evaluable patients, hematological improvement occurred in 4/14 (28.6%) patients with an IPF > 6.8% and in 5/8 (62.5%) with an IPF ≤ 6.8% ( p = 0.187). IPF is an investigational biomarker and requires validation in adequately powered multicenter cohorts.