title: Evidence that prefibrotic myelofibrosis is aligned along a clinical and biological continuum featuring primary myelofibrosis.
abstract: OBJECTIVE
  In the WHO diagnostic classification, prefibrotic myelofibrosis (pre-MF) is included in the category of primary myelofibrosis (PMF). However, strong evidence for this position is lacking.
  
  
  METHODS
  We investigated whether pre-MF may be aligned along a clinical and biological continuum in 683 consecutive patients who received a WHO diagnosis of PMF.
  
  
  RESULTS
  As compared with PMF-fibrotic type, pre-MF (132 cases) showed female dominance, younger age, higher hemoglobin, higher platelet count, lower white blood cell count, smaller spleen index and higher incidence of splanchnic vein thrombosis. Female to male ratio and hemoglobin steadily decreased, while age increased from pre-MF to PMF- fibrotic type with early and to advanced bone marrow (BM) fibrosis. Likely, circulating CD34+ cells, LDH levels, and frequency of chromosomal abnormalities increased, while CXCR4 expression on CD34+ cells and serum cholesterol decreased along the continuum of BM fibrosis. Median survival of the entire cohort of PMF cases was 21 years. Ninety-eight, eighty-one and fifty-six percent of patients with pre-MF, PMF-fibrotic type with early and with advanced BM fibrosis, respectively, were alive at 10 years from diagnosis.
  
  
  CONCLUSIONS
  Pre-MF is a presentation mode of PMF with a very indolent phenotype. The major consequences of this contention is a new clinical vision of PMF, and the need to improve prognosis prediction of the disease.
authors.affiliation: Laboratory of Clinical Epidemiology and Centre for the Study of Myelofibrosis, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy. barosig@smatteo.pv.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barosi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rosti
authors.forename: Elisa
authors.initials: E
authors.lastname: Bonetti
authors.forename: Rita
authors.initials: R
authors.lastname: Campanelli
authors.forename: Adriana
authors.initials: A
authors.lastname: Carolei
authors.forename: Paolo
authors.initials: P
authors.lastname: Catarsi
authors.forename: Antonina M
authors.initials: AM
authors.lastname: Isgrò
authors.forename: Letizia
authors.initials: L
authors.lastname: Lupo
authors.forename: Margherita
authors.initials: M
authors.lastname: Massa
authors.forename: Valentina
authors.initials: V
authors.lastname: Poletto
authors.forename: Gianluca
authors.initials: G
authors.lastname: Viarengo
authors.forename: Laura
authors.initials: L
authors.lastname: Villani
authors.forename: Umberto
authors.initials: U
authors.lastname: Magrini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D055728:Primary Myelofibrosis / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D014944:World Health Organization; D055815:Young Adult
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2