title: 13-cis retinoic acid treatment for myelodysplastic syndromes.
abstract: To test the biologic activity of 13-cis retinoic acid (13-CRA) in patients with myelodysplastic states (MDS), we administered 13-CRA orally (2.5 mg/kg/d initially, escalated to 4 mg/kg/d) for 8 weeks to 15 consecutive patients. Eight of 15 patients (53%) experienced an increase in peripheral granulocyte counts of greater than 20% (range, 22% to 700%). In five patients, the absolute increase in peripheral granulocyte count was greater than 500 cells/microL. Two of 15 patients experienced a decrease in the circulating granulocyte count of greater than or equal to 20%. Comparable values for peripheral platelet counts were 27% (4/15 patients) greater than 20% increase and 33% (5/15 patients) greater than 20% decrease. No patient experienced a major change in erythrocyte transfusion requirement while receiving 13-CRA in comparison with pretreatment status. Thirteen patients had morphologic and cytogenetic evaluation of marrow cells before 13-CRA treatment, and with one exception, marrow morphologic and cytogenetic abnormalities persisted following 13-CRA administration. The exception occurred in the patient with the most dramatic response, whose granulocyte count increased from 400 to 2,800 cells/microL along with a normalization of the leukocyte alkaline phosphatase score, a morphologic improvement in granulocyte maturation, and a disappearance of the initial chromosome abnormality. These changes did not persist after cessation of 13-CRA administration, but were reproduced following drug readministration. No patients experienced serious decrements in peripheral blood counts or leukemic transformation while receiving 13-CRA. All patients had mild to marked dermatologic toxicity (cheilosis, skin dryness). No other major toxicity was encountered. We conclude that 13-CRA may be safely administered and may increase peripheral granulocyte counts in a proportion of patients with MDS.
mesh_terms: D000328:Adult; D000368:Aged; D001803:Blood Transfusion; D001853:Bone Marrow / Q000473:pathology; D002986:Clinical Trials as Topic; D005260:Female; D006098:Granulocytes / Q000166:cytology; D006801:Humans; D015474:Isotretinoin; D007621:Karyotyping; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D010976:Platelet Count; D014212:Tretinoin / Q000627:therapeutic use*
chemical_list: D014212:Tretinoin; D015474:Isotretinoin