Should ATRA be held in a patient with acute promyelocytic leukemia and a high WBC count?

Associate professor of medicine at the Washington University School of Medicine in St. Louis, Missouri

This month, Geoffrey L. Uy, MD, answers a question about white blood cell counts in a patient being treated for acute promyelocytic leukemia.

CLINICAL DILEMMA

A 52-year-old man with low-risk acute promyelocytic leukemia (APL) presenting with a white blood cell (WBC) count of 3,200 and a platelet count of 70,000 was started on all-trans-retinoic acid (ATRA) + arsenic trioxide. The patient experienced a rise in WBC count from 16,000 on day 12 to 25,000 on day 20 – despite starting dexamethasone on day 15. The patient experienced bilateral swelling in the lower extremities with no effusion. I am concerned about differentiation syndrome and the continued rise in WBC count, despite treatment with 10 mg dexamethasone delivered every 12 hours.

Should ATRA be held until WBC count improves, or should the patient be started on idarubicin or another agent?

EXPERTS MAKE THE CALL

 In this setting, steroids like dexamethasone are thought to reduce the risk of complications from differentiation syndrome; however, they really do not have any effect on the leukocytosis associated with ATRA + arsenic trioxide.

If the patient is clinically stable, our practice is to continue treatment. We would only hold treatment in cases of severe differentiation syndrome, i.e. the patient was significantly hypoxic, experiencing pericardial/pleural effusions, or was hypotensive.

For the leukocytosis, we generally treat the patient with hydroxyurea, in a regimen outlined in The New England Journal of Medicine. Their treatment guidelines are as follows: In patients developing leukocytosis after treatment initiation, hydroxyurea is administered at the dosage of 500 mg once-daily for WBC between 10 and 50 x 109/L, and 1.0 g once-daily for WBC >50 x 109/L. Hydroxyurea was discontinued when WBC count was again <10 x 109/L.

Reference

Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369:111-21.

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