Haematologica | 2019
Positive impact of molecular analysis on prognostic scores in essential thrombocythemia: a single center prospective cohort experience
Abstract
Classical Philadelphia-negative myeloproliferative syndromes (MPN) are characterized by the presence of driver mutations (JAK2, CALR or MPL) and comprise polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The prognosis of ET is highly variable from one patient to another and is related to two major risks of complications: an increased risk for thrombosis (the most frequent) and a risk of hematological transformation (the most severe) into secondary myelofibrosis or acute leukemia. Different prognostic scoring systems based on clinical (age, history of thrombosis) and biological factors (leukocyte count, driver mutation) have been developed in ET. Since the milestone study from Vannucchi et al., additional mutations have been clearly demonstrated as important prognostic factors in PMF but, to date, few data are available in ET. In this study, we analyzed prognostic factors and validated scoring systems in a single center cohort of ET patients, and we evaluated the additive impact of NGS analysis. The cohort consisted of 190 consecutive ET patients diagnosed at the Henri Mondor hospital between January 2000 and December 2016 (patients’ clinical and biologic characteristics at diagnosis are summarized in Online Supplementary Table S1). All patients meet the ET WHO 2008 criteria for diagnosis. With a median follow up of 6.4 years, thrombosis occurred in 18 cases (9.4%) and transformation into myelofibrosis, myelodysplastic syndrome or acute myeloid leukemia was observed in 11 cases (5.7%). A total of 16 deaths (8.4%) were observed during the follow up. Driver molecular mutations were as follow: JAK2V617F (allelic burden over 0.5%) in 116 patients (61.1 %), CALR mutations in 27 patients (14.2%, of which 15 are del52 (type 1), 8 ins5 (type 2) and 4 other mutations inducing a similar frameshift (details in Online Supplementary Table S2)) and MPLW515K/Lmutation in 4 patients (2.1%). Triple negative patients represented 22.6% of the cohort (n= 43). CALR mutations were previously associated with a favorable prognosis in ET. In this study we failed to draw a conclusion about the prognostic impact of these mutations, probably due to the small number of CALR mutated cases.