Leukemic transformation among 1306 patients with primary myelofibrosis: risk factors and development of a predictive model

Rangit R. Vallapureddy, Mythri Mudireddy, Domenico Penna, Terra L. Lasho, Christy M. Finke, Curtis A. Hanson, Rhett P. Ketterling, Kebede H. Begna, Naseema Gangat, Animesh Pardanani, Ayalew Tefferi

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Among 1306 patients with primary myelofibrosis (PMF), we sought to identify risk factors that predicted leukemic transformation (LT) in the first 5 years of disease and also over the course of the disease. 149 (11%) LT were documented; patients who subsequently developed LT (n = 149), compared to those who remained in chronic phase disease (n = 1,157), were more likely to be males (p = 0.02) and display higher circulating blasts (p = 0.03), ASXL1 (p = 0.01), SRSF2 (p = 0.001) and IDH1 (p = 0.02) mutations. Logistic regression analysis identified IDH1, ASXL1 and SRSF2 mutations, very high-risk karyotype, age > 70 years, male sex, circulating blasts ≥ 3%, presence of moderate or severe anemia and constitutional symptoms, as predictors of LT in the first 5 years of diagnosis. Time-to-event Cox analysis confirmed LT prediction for IDH1 mutation (HR 4.3), circulating blasts ≥ 3% (HR 3.3), SRSF2 mutation (HR 3.0), age > 70 years (HR 2.1), ASXL1 mutation (HR 2.0) and presence of moderate or severe anemia (HR 1.9). HR-based risk point allocation resulted in a three-tiered LT risk model: high-risk (LT incidence 57%; HR 39.3, 95% CI 10.8–114), intermediate-risk (LT incidence 17%; HR 4.1, 95% CI 2.4–7.3) and low-risk (LT incidence 8%). The current study provides a highly discriminating LT predictive model for PMF.

Original languageEnglish (US)
Article number12
JournalBlood cancer journal
Volume9
Issue number2
DOIs
StatePublished - Feb 1 2019

ASJC Scopus subject areas

  • Hematology
  • Oncology

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