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Leukemia. 2015 Jun;29(6):1344-9. doi: 10.1038/leu.2015.87. Epub 2015 Mar 24.

Mutations and long-term outcome of 217 young patients with essential thrombocythemia or early primary myelofibrosis.

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Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology 'L. and A. Seràgnoli', University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
Division of Hematology, Azienda Ospedaliera Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
Section of Hematology and BMT Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
Division of Hematology, Azienda Ospedaliera 'Bianchi Melacrino Morelli', Reggio Calabria, Italy.


We investigated the influence of molecular status on disease characteristics and clinical outcome in young patients (⩽ 40 years) with World Health Organization (WHO)-defined essential thrombocythemia (ET) or early/prefibrotic primary myelofibrosis (early-PMF). Overall, 217 patients with ET (number 197) and early-PMF (number 20) were included in the analysis. Median follow-up time was 10.2 years. The cumulative incidence of thrombosis, hemorrhages and disease evolution into myelofibrosis/acute leukemia were 16.6%, 8.6% and 3% at 15 years, respectively. No differences were detectable between ET and early-PMF patients, although the latter cohort showed a trend for worse combined-event free survival (EFS). Mutation frequency were 61% for JAK2V617F, 25% for CALR and 1% for MPLW515K, and were comparable across WHO diagnosis; however, JAK2V617F allele burden was higher in the early-PMF group. Compared with JAK2V617F-positive patients, CALR-mutated patients displayed higher platelet count and lower hemoglobin level. CALR mutations significantly correlated with lower thrombotic risk (9.1% versus 21.7%, P = 0.04), longer survival (100% versus 96%, P = 0.05) and better combined-EFS (86% versus 71%, P = 0.02). However, non-type 1/type 2 CALR mutations ('minor' mutations) and abnormal karyotype were found to correlate with increased risk of disease evolution. At last contact, six patients had died; in five cases, the causes of death were related to the hematological disease and occurred at a median age of 64 years (range: 53-68 years). Twenty-eight patients (13%) were unmutated for JAK2, CALR and MPL: no event was registered in these 'triple-negative' patients.

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