A phase-II trial of all trans retinoic acid and low-dose cytosine arabinoside for the treatment of high-risk myelodysplastic syndromes

Twenty-two patients with high-risk myelodysplastic syndrome (HRMDS) were tr eated with a 10-day course of oral all trans retinoic acid (45 mg/m(2)) and s.c. low-dose cytosine arabinoside (LDARAc) given at the dose of 20 mg twi ce per day. The courses were repeated monthly until response or progression ; in the case of response, the therapy was administered until relapse. Morp hologic diagnoses were refractory anemia with excess blasts (RAEB) in nine, RAEB in transformation (RAEB-t) in nine, and chronic myelomonocytic leukem ia (CMMoL) in four patients: in all cases, bone-marrow blast: infiltration was greater than 10% (median 20%, range 12-30%). When the international pro gnostic scoring system was applied, all the cases qualified as intermediate /high-risk categories. Nineteen patients were males and three were females: the median age was 69 years (range 25-90 years); three patients had previo usly been treated with conventional chemotherapy, and one of them had also undergone autologous bone-marrow transplantation. The: criteria of response were defined as follows: (1) complete response: normalization of blood cou nts and bone-marrow blasts (< 5%), and (2) partial response: decrease in bo ne-marrow blast infiltration by 50%, and two of the following parameters - improvement in hemoglobin level by 1.5 g/dl or decrease by 50% in transfusi onal requirement, increase by 50% in absolute neutrophil count, and increas e by 50% in platelet count. Overall. 7 (32%) of 22 patients achieved a resp onse, with 5 (23%) being classified as complete responders and 2 (9%) as pa rtial responders. Fifteen (68%) patients did not achieve any response, and 14 died of progressive disease or infectious disease. The overall median su rvival was 8 months (range 1-27 months), whereas the median survival of res ponders was 16 months (range 8-27 months); the median duration of response was 11 months (range 2-21 months). Moderate to severe hematological toxicit y and infections were the most common side effects. In conclusion, it seems that the association of ATRA and LDARA-C may be effective in approximately 30% of HRMDS patients. Optimizing this approach might be pursued by select ing, on a biological basis, those cases more likely to respond or by incorp orating other differentiating agents or growth factors.