Disappearance of cytogenetic abnormalities and clinical remission during therapy with 13-cis-retinoic acid in a patient with myelodysplastic syndrome: inhibition of growth of the patient's malignant monocytoid clone.

Median survival is as little as 6 months for patients with refractory anemia with excess blasts who demonstrate an abnormal karyotype in the majority of marrow cells. We treated a patient who presented with 29% marrow blasts and 90% abnormal metaphases with 13-cis-retinoic acid. He achieved a complete clinical and cytogenetic remission during therapy. To determine the mechanism of the response, serial studies were done of the effects of 13-cis-retinoic acid and dexamethasone on in vitro growth of his marrow cells. During clinical remission, when the drug was not administered, marrow growth remained significantly depressed. During relapse, the remission growth pattern was replaced by overgrowth of the karyotypically abnormal monocytoid clone. Clonal growth occurred in cultures containing colony-stimulating activity or dexamethasone but was absent in cultures containing concentrations of 13-cis-retinoic acid achieved in vivo. After the drug was reinstituted, a second clinical stabilization developed. Since 13-cis-retinoic acid inhibits normal monocyte colony growth, we postulate that the patient's unusual clinical responses to the drug were due to in vivo growth inhibition of the malignant monocytoid clone.