Circulating hematopoietic progenitor cells predict survival in patients with myelofibrosis with myeloid metaplasia

Abstract

BACKGROUND AND OBJECTIVES: The levels of circulating hematopoietic progenitor cells are often increased in myelofibrosis with myeloid metaplasia (MMM). The prognostic relevance of this phenomenon is largely unknown. DESIGN AND METHODS: We determined the number of circulating myeloid (CFU-GM), erythroid (BFU-E), and pluripotent (CFU-GEMM) progenitors, in 110 patients with MMM at diagnosis using a semi-solid colony assay. Overall survival was investigated by plots of the Kaplan-Meier estimator; known risk factors and the number of circulating progenitor cells were tested by univariate and multiple Cox regression analysis. RESULTS: Univariate analysis showed that hemoglobin concentration (p=0.019), CFU-GM (p< 0.0001), BFU-E (p=0.002), and age (p=0.002) predicted survival. Numbers of circulating CFU-GM above the 75th percentile were associated with a significantly shorter survival than were CFU-GM levels at or below the 75th percentile (27 vs. 74 months, p=0.0007). Similarly, high numbers of BFU-E in peripheral blood (> 75th percentile) predicted a shorter survival (33 vs. 74 months; p=0.007). When myeloid and erythroid progenitor cells were calculated separately in the multiple Cox regression analysis, both CFU-GM (hazard ratio 2.8, 95% CI, 1.35 to 5.93) and BFU-E (hazard ratio 2.57, 95% CI, 1.26 to 5.21) numbers above the 75th percentile were independent adverse prognostic factors in our patients. INTERPRETATION AND CONCLUSIONS: High levels of circulating myeloid and erythroid progenitor cells are novel risks factors in patients with MMM. The assessment of hematopoietic progenitor cells may be useful to determine risk-adjusted treatment strategies.