title: Diagnosis according to World Health Organization determines the long-term prognosis in patients with myeloproliferative neoplasms treated with anagrelide: results of a prospective long-term follow-up.
abstract: OBJECTIVE
  During long term follow-up of a cohort of patients with essential thrombocythemia (ET) and polycythemia vera (PV) a higher than expected incidence of myelofibrosis (MF) was noted. In order to test if the explanation could be found in the diagnostic criteria a re-evaluation  of diagnosis using the 2008 WHO diagnostic criteria for ET and MF was performed.
  
  
  METHODS
  This prospective study of 60 patients with ET and PV was set up in 1998 to evaluate the long-term efficacy and tolerability of anagrelide treatment. Bone marrow trephine biopsies were  requested from study start, after 2 and 7 years of follow-up. A blinded re-evaluation of the bone marrow trephines was performed. The 2008 WHO bone marrow criteria were used for diagnosis and fibrosis grading.
  
  
  RESULTS
  Of 40 patients with an initial diagnosis of ET, 21 were  confirmed as 'true ET' whereas 17 were reclassified as primary myelofibrosis (PMF) (12 PMF-0, 3 PMF-1, 2 PMF-2) and 2 as myeloproliferative neoplasms of uncertain origin. After 7 years of follow-up, 19 of 21 patients with 'true ET' were alive, none had transformed to  MF, leukemia, or myelodysplastic syndrome. In contrast, 4/17 patients reclassified as PMF had died, two patients transformed to myelodysplastic syndrome and 7 patients progressed to overt MF.
  
  
  CONCLUSIONS
  We conclude that a blinded re-evaluation of bone marrow trephines from  study start and after 7 years of follow-up using 2008 World Health Organization criteria was able to differentiate between true ET and PMF with a marked difference in follow-up outcome.
authors.affiliation: Department of Hematology, Uppsala University, Sweden. elisabeth.ejerblad@akademiska.se
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ejerblad
authors.forename: Hans M
authors.initials: HM
authors.lastname: Kvasnicka
authors.forename: Jürgen
authors.initials: J
authors.lastname: Thiele
authors.forename: Björn
authors.initials: B
authors.lastname: Andreasson
authors.forename: Magnus
authors.initials: M
authors.lastname: Björkholm
authors.forename: Eva
authors.initials: E
authors.lastname: Löfvenberg
authors.forename: Berit
authors.initials: B
authors.lastname: Markevärn
authors.forename: Mats
authors.initials: M
authors.lastname: Merup
authors.forename: Lars
authors.initials: L
authors.lastname: Nilssson
authors.forename: Jan
authors.initials: J
authors.lastname: Palmblad
authors.forename: Jan
authors.initials: J
authors.lastname: Samuelsson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Birgegård
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000175:diagnosis* / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011379:Prognosis; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D014944:World Health Organization
chemical_list: D010975:Platelet Aggregation Inhibitors; D011799:Quinazolines; C021139:anagrelide