title: Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study.
abstract: OBJECTIVE
  The WHO diagnostic criteria underscore the role of bone marrow (BM) morphology in distinguishing essential thrombocythemia (ET) from early/prefibrotic primary myelofibrosis (PMF). This study examined the clinical relevance of such a distinction.
  
  
  METHODS
  Representatives from seven international centers of excellence for myeloproliferative neoplasms convened to create a clinicopathologic database of patients previously diagnosed as having ET (N = 1,104). Study eligibility criteria included availability of treatment-naive BM specimens obtained within 1 year of diagnosis. All bone marrows subsequently underwent a central re-review.
  
  
  RESULTS
  Diagnosis was confirmed as ET in 891 patients (81%) and was revised to early/prefibrotic PMF in 180 (16%); 33 patients were not evaluable. In early/prefibrotic PMF compared with ET, the 10-year survival rates (76% and 89%, respectively) and 15-year survival rates (59% and 80%, respectively), leukemic transformation rates at 10 years (5.8% and 0.7%, respectively) and 15 years (11.7% and 2.1%, respectively), and rates of progression to overt myelofibrosis at 10 years (12.3% and 0.8%, respectively) and 15 years (16.9% and 9.3%) were significantly worse. The respective death, leukemia, and overt myelofibrosis incidence rates per 100 patient-years for early/prefibrotic PMF compared with ET were 2.7% and 1.3% (relative risk [RR], 2.1; P < .001), 0.6% and 0.1% (RR, 5.2; P = .001), and 1% and 0.5% (RR, 2.0; P = .04). Multivariable analysis confirmed these findings and also identified age older than 60 years (hazard ratio [HR], 6.7), leukocyte count greater than 11 × 10(9)/L (HR, 2.01), anemia (HR, 2.95), and thrombosis history (HR, 2.81) as additional risk factors for survival. Thrombosis and JAK2V617F incidence rates were similar between the two groups. Survival in ET was similar to the sex- and age-standardized European population.
  
  
  CONCLUSIONS
  This study validates the clinical relevance of strict adherence to WHO criteria in the diagnosis of ET and provides important information on survival, disease complication rates, and prognostic factors in strictly WHO-defined ET and early/prefibrotic PMF.
authors: Ospedali Riuniti di Bergamo, Bergamo, Italy.
authors: Tiziano
authors: T
authors: Barbui
authors: Juergen
authors: J
authors: Thiele
authors: Francesco
authors: F
authors: Passamonti
authors: Elisa
authors: E
authors: Rumi
authors: Emanuela
authors: E
authors: Boveri
authors: Marco
authors: M
authors: Ruggeri
authors: Francesco
authors: F
authors: Rodeghiero
authors: Emanuele S G
authors: ES
authors: d'Amore
authors: Maria Luigia
authors: ML
authors: Randi
authors: Irene
authors: I
authors: Bertozzi
authors: Filippo
authors: F
authors: Marino
authors: Alessandro M
authors: AM
authors: Vannucchi
authors: Elisabetta
authors: E
authors: Antonioli
authors: Valentina
authors: V
authors: Carrai
authors: Heinz
authors: H
authors: Gisslinger
authors: Veronika
authors: V
authors: Buxhofer-Ausch
authors: Leonhard
authors: L
authors: Müllauer
authors: Alessandra
authors: A
authors: Carobbio
authors: Andrea
authors: A
authors: Gianatti
authors: Naseema
authors: N
authors: Gangat
authors: Curtis A
authors: CA
authors: Hanson
authors: Ayalew
authors: A
authors: Tefferi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D055728:Primary Myelofibrosis / Q000175:diagnosis* / Q000401:mortality; D016016:Proportional Hazards Models; D012307:Risk Factors; D013920:Thrombocythemia, Essential / Q000175:diagnosis* / Q000401:mortality; D014944:World Health Organization; D055815:Young Adult