title: Mutations and long-term outcome of 217 young patients with essential thrombocythemia or early primary myelofibrosis.
abstract: 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.
authors: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology 'L. and A. Seràgnoli', University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: F
authors: F
authors: Palandri
authors: Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
authors: R
authors: R
authors: Latagliata
authors: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology 'L. and A. Seràgnoli', University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: N
authors: N
authors: Polverelli
authors: Division of Hematology, Azienda Ospedaliera Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
authors: A
authors: A
authors: Tieghi
authors: Section of Hematology and BMT Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors: M
authors: M
authors: Crugnola
authors: Division of Hematology, Azienda Ospedaliera 'Bianchi Melacrino Morelli', Reggio Calabria, Italy.
authors: B
authors: B
authors: Martino
authors: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology 'L. and A. Seràgnoli', University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: M
authors: M
authors: Perricone
authors: Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
authors: M
authors: M
authors: Breccia
authors: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology 'L. and A. Seràgnoli', University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: E
authors: E
authors: Ottaviani
authors: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology 'L. and A. Seràgnoli', University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: N
authors: N
authors: Testoni
authors: Division of Hematology, Azienda Ospedaliera Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
authors: F
authors: F
authors: Merli
authors: Section of Hematology and BMT Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors: F
authors: F
authors: Aversa
authors: Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
authors: G
authors: G
authors: Alimena
authors: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology 'L. and A. Seràgnoli', University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: M
authors: M
authors: Cavo
authors: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology 'L. and A. Seràgnoli', University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: G
authors: G
authors: Martinelli
authors: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology 'L. and A. Seràgnoli', University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: L
authors: L
authors: Catani
authors: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology 'L. and A. Seràgnoli', University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: M
authors: M
authors: Baccarani
authors: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology 'L. and A. Seràgnoli', University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: N
authors: N
authors: Vianelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D037282:Calreticulin / Q000235:genetics*; D015331:Cohort Studies; D020732:Cytogenetic Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D055728:Primary Myelofibrosis / Q000235:genetics* / Q000401:mortality*; D011379:Prognosis; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D015996:Survival Rate; D013920:Thrombocythemia, Essential / Q000235:genetics* / Q000401:mortality*; D055815:Young Adult
chemical_list: C576483:CALR protein, human; D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2