Primary myelofibrosis with increased haemoglobin concentration at presentation.

One hundred of 963 consecutive registrants with primary myelofibrosis (PMF) in the Pavia-CSM database had haemoglobin concentration at diagnosis ≥160 g/L in females or ≥ 165 g/L in males. These subjects were more often female and younger; had higher white blood cell (WBC) and platelet concentrations; and higher frequency of JAK2V617F and JAK2V617F variant allele frequency (VAF) compared with those without increased haemoglobin at diagnosis. They had less active disease defined as smaller spleen, lower plasma lactate dehydrogenase, lower blood CD34-positive cell concentration and less bone marrow fibrosis. They also had a lower plasma high-sensitivity C-reactive protein concentration consistent with less inflammation. These subjects were more likely to evolve towards an increased WBC concentration and had a lower risk of progressing to a myelodepletive phenotype compared with those without increased haemoglobin concentration at diagnosis and longer survival (22 vs. 15 years; p < 0.001). In subjects with increased haemoglobin concentration at diagnosis, age >50 years and JAK2V617F VAF > 75% correlated with worse survival. Our findings suggest that PMF with increased haemoglobin concentration at diagnosis is a unique variant characterized by JAK2V617F-driven hyperproliferation with less inflammation. These features impact prognosis and therapy.