ALL-Trans Retinoic Acid (ATRA) in the Treatment of Myelodysplastic Syndromes: Results in 5 Cases

Abstract

<i>Background</i>: Isotretinoin has been used in the past as a differentiation-inducing agent in myelodysplastic syndrome (MDS). ATRA is another retinoic acid derivative and a main therapeutic option in the treatment of acute promyelocytic leukemia (APL). We report the results with ATRA on 5 patients with MDS. <i>Patients and Results</i>: Five patients, 54 to 82 years of age, have been treated with ATRA at a dose level of 45 mg/m² for a period of 3 up to 9 weeks. Diagnosis according to the FAB classification was refractory anemia (RA; 1 case), refractory anemia with excess of blasts (RAEB; 3 cases), and refractory anemia with excess of blasts in transformation (RAEB-t; 1 case). In the preleukemic cases with blast excess, cyto-toxic chemotherapy had been withheld according to age and/or comorbidity. Three patients were treated in a phase II multicenter trial with recombinant human erythropoietin (rh-EPO), 2 of these prior to ATRA therapy, another patient after failure of ATRA therapy. Alltogether these 3 patients failed to respond to rh-EPO. Because of severe granulocytopenia and intermittent infectious complications a simultaneous administration of granulocyte colony-stimulating factor (G-CSF) was necessary in 3 patients. However, ATRA treatment did not show any benefit in case of RAEB, RAEB-t such as prolongation of the transfusion interval for red blood cells or increase of peripheral cell count of any lineage. In one patient with RA we observed a marginal therapeutic activity of ATRA. A prolongation of the transfusion interval with red blood cells (RBC) from 7.1 to 17.2 days has been documented, and an increase in platelet count from 59/nl to a maximum of 158/nl as well. The major side effects in all patients we observed were moderate hypertriglyceridemia, muco-cutaneous dryness, and pruritus. In the partial responding female patient, ATRA treatment had to be cessated because of severe arthralgias and ophthalmic keratitis. <i>Conclusion</i>: In contrast to the remarkable activity in the treatment of APL, in our 5 MDS cases ATRA exhibited no major therapeutic activity, particularly in the 4 preleukemic RAEB cases.