Use of erythropoiesis-stimulating agents by patients with primary myelofibrosis appears to be an independent risk factor for leukemic transformation, according to a presentation at the annual meeting of the American Society of Hematology.

Mayo Clinic researchers evaluated the records of 311 Clinic patients with primary myelofibrosis treated between 1976 and 2006. At an average follow-up of 27 months, 27 cases (9 percent) of leukemic transformation were documented.

"We believe this to be the first large systematic evaluation of the risk factors leading to leukemic transformation in primary myelofibrosis," said Jocelin Huang, MD, hematology researcher at Mayo Clinic. "And in the process, we discovered some unexpected results."

The researchers confirmed a number of clinical and laboratory variables that appeared to correlate with leukemic transformation. Independent risk factors for development of leukemia included peripheral blood blast levels greater than or equal to 3 percent and a platelet count of less than 100x109/liter. The more surprising findings were that specific treatments also appeared to be related to leukemic transformation. Use of erythrocyte-stimulating agents or Danazol (danocrine, a weak androgen that has anemia-countering properties) were linked to later development of leukemia independent of the blast or platelet levels.

Ayalew Tefferi, MD, principal investigator of the study, and a Mayo Clinic hematologist, cautioned that the current findings are based on retrospective observation and need to be validated in properly designed prospective studies. "While we cannot take these findings as an absolute, at the same time, they cannot be ignored," said Tefferi. "Treatment decisions regarding the use of erythrocyte-stimulating agents in patients with primary myelofibrosis should carefully be evaluated."

Other factors that appeared to contribute to development of leukemia included anemia, leukocytosis and peripheral blood monocyte count greater than or equal to 1x109/L, hypercatabolic symptoms, splenectomy and treatment with androgens. However, they were not independent predictors.