title: Risk factors for leukemic transformation in patients with primary myelofibrosis.
abstract: BACKGROUND
  Previous prognostic studies in primary myelofibrosis have focused on risk factors for overall survival and have resulted in the establishment of several prognostic scoring systems. However, to the authors' knowledge, information regarding risk factors for leukemic transformation in primary myelofibrosis is limited.
  
  
  METHODS
  The current retrospective study examined clinical variables at the time of diagnosis and specific treatment modalities for their effect on leukemic transformation in 311 patients with primary myelofibrosis who were seen at the Mayo Clinic.
  
  
  RESULTS
  Univariate analysis of parameters at the time of diagnosis revealed a significant association between inferior leukemia-free survival and a peripheral blood blast percentage>or=3 (P<.0001), a platelet count<100x10(9)/L (P=.004), a monocyte count>or=1x10(9)/L (P=.02), the presence of hypercatabolic symptoms (P=.03), a low hemoglobin level (P=.04), and a high leukocyte count (P=.04). The first 2 parameters were found to maintain their statistical significance during multivariate analysis. Neither leukemia-free nor overall survival was found to be affected by the presence of <3% peripheral blood blasts or JAK2V617F mutation. The evaluation of treatment effect on leukemic transformation unexpectedly revealed a significant and independent association with previous therapy with either erythropoiesis-stimulating agents (P=.004) or danazol (P=.007), even when the aforementioned prognostic indicators at the time of diagnosis were added as covariates to the multivariate model. In contrast, leukemia-free survival was not found to be affected by a treatment history with hydroxyurea, thalidomide, or other drugs.
  
  
  CONCLUSIONS
  A peripheral blood blast percentage>or=3 and/or a platelet count<100x10(9)/L at the time of diagnosis were found to be strong and independent predictors of leukemic transformation in patients with primary myelofibrosis. The unexpected association between leukemic transformation and a history of treatment with erythropoiesis-stimulating agents or danazol requires validation by prospective studies.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Jocelin
authors.initials: J
authors.lastname: Huang
authors.forename: Chin-Yang
authors.initials: CY
authors.lastname: Li
authors.forename: Ruben A
authors.initials: RA
authors.lastname: Mesa
authors.forename: Wentling
authors.initials: W
authors.lastname: Wu
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.forename: Animesh
authors.initials: A
authors.lastname: Pardanani
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D002471:Cell Transformation, Neoplastic; D003613:Danazol / Q000009:adverse effects; D004921:Erythropoietin / Q000009:adverse effects; D005260:Female; D006801:Humans; D007938:Leukemia / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D055728:Primary Myelofibrosis / Q000150:complications* / Q000188:drug therapy; D012307:Risk Factors
chemical_list: D004921:Erythropoietin; D003613:Danazol