ALL-TRANS-RETINOIC ACID IN THE TREATMENT OF MYELODYSPLASTIC SYNDROMES

Myelodysplastic syndromes (MDS) are a group of hematopoietic disorders characterized by uni- or multilineage maturation defects of the bone marrow. Controversial therapeutic results have been obtained using gro wth factors or differentiating agents such as 13-cis retinoic acid. In this pilot study we evaluated the effects of all-trans retinoic acid (ATRA) in 10 MDS patients (5 male, 5 female). Six patients had refract ory anemia (RA), I had refractory anemia with excess of blasts (RAEB), and 3 had refractory anemia with excess of blasts in transformation ( RAEB-t). All patients received the same dose of ATRA (45 mg/sqm/day) o rally for 6 weeks. A rise in hemoglobin concentration >1 g/dl was obse rved in 3/10 patients, while 5/10 patients showed an increase in granu locyte count >0.5 x 10(9)/l without concomitant increase in the percen tage of blast cells in the bone marrow. A rise in the platelet count > 50 x 10(9)/l was observed in 1/10 patients. All the effects were trans ient and maximal responses were obtained by the fourth week of treatme nt. Thereafter, the peripheral blood counts started to drop again, rea ching pre-therapy values by the end of the treatment. This phenomenon could be attributed either to the exhaustion of an ATRA-responding cel l pool, the development of cellular resistance to ATRA or to a reducti on of plasma ATRA levels after prolonged treatment. According to our r esults, it seems that ATRA might have therapeutic efficacy in MDS, par ticularly if its effect could be improved by combinations with other d ifferentiating agents or growth factors.