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 JAK2^V617F and JAK2^V617F 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 JAK2^V617F VAF > 75% correlated with worse survival. Our findings suggest that PMF with increased haemoglobin concentration at diagnosis is a unique variant characterized by JAK2^V617F-driven hyperproliferation with less inflammation. These features impact prognosis and therapy.