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Evidence links anemia drugs with leukemic transformation in patients with primary myelofibrosis

ATLANTA -- Mayo Clinic researchers today reported the discovery of a link between erythropoiesis-stimulating agents (ESAs) and leukemic transformation (conversion to leukemia) of the blood disorder myelofibrosis. The results of the retrospective study, which sought to quantify the risk factors for leukemic transformation, were presented by lead author Jocelin Huang, M.D., at the American Society of Hematologys annual meeting.

We believe this to be the first large systematic evaluation of the risk factors leading to leukemic transformation in primary myelofibrosis, says Dr. Huang, 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 (immature leukemia cells) levels greater than or equal to 3 percent; and a platelet count of less than 100x109/liter (L). The more surprising findings were that specific treatments also appeared to be related to leukemic transformation. Use of ESAs or danazol (a hormone with anemia-countering properties) were linked to later development of leukemia, independent of the blast or platelet levels.

Ayalew Tefferi, M.D., principal investigator of the study, and a Mayo Clinic hematologist, cautions 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, says Dr. Tefferi. Treatment decisions regarding the use of ESAs in patients with primary myelofibrosis should carefully be evaluated.

He also points out that ESA treatment in patients with primary myelofibrosis has the potential to cause further enlargement of the spleen (a known complication of the disease).

The study evaluated the records of 311 Mayo Clinic patients, seen with primary myelofibrosis between 1976 and 2006. Of these patients, at an average follow-up of 27 months, 27 cases (9 percent) of leukemic transformation were documented.

Other factors appeared to contribute to the development of leukemia, including anemia, leukocytosis and peripheral blood monocyte count greater than or equal to 1x109/L (both are measures of elevated white blood cells), hypercatabolic symptoms (results of excess metabolism), a splenectomy and treatment with androgens (a type of hormones). However, they were not independent predictors.


Contact: Elizabeth Zimmermann
Mayo Clinic

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