Treatment of Del(5q) Myelodysplastic Syndrome with All-Trans-Retinoic Acid and Tocopherol-α.

All-trans-retinoic acid (ATRA) alone or in combination with cytokines and vitamins has shown erythroid remitting capacities in low-grade myelodysplastic syndromes (MDS). We performed a phase II study on 29 patients with MDS and isolated del(5q) including bands 5q31–5q33 to determine the efficacy and safety of ATRA in combination with tocopherol-α. All patients had low/intermediate-1 risk MDS according to the international prognostic scoring system. Inclusion criteria were isolated del(5q), medullary blast count of <10%, hemoglobin <10g/dl or transfusion dependent anemia, and ECOG performance score <3. Included were 18 women and 11 men. Median age of patients was 64 years. FAB subtypes were 25 refractory anemias, 1 refractory anemia with ring sideroblasts, 3 refractory anemias with excess of blasts. Median MDS duration before ATRA treatmnet was 31.7 months. Median hemoglobin level was 8.4 g/dl at study entry. Patients received 45 mg/m² ATRA day 1 to 90, and 90 mg/m² day 91 to 180. Tocopherol dosage was 600 IU three times daily. 24 patients completed dose level I, 12 patients dose level II. 86% of patients experienced side effects. 13 interrupted study drug treatment due to adverse events: Skin reactions (NCI grade 3), conjunctivitis (grade 3), headache and joint pain (grade 3) were the worst recorded. Other adverse events included hair loss, CNS symptoms, cheilitis, stomatitis, creatinine elevation, hypertriglyceridemia, hypercholesterinemia, nausea and vomiting, and elevation of liver function tests. 3 patients were admitted to hospital for side effects and these were therefore qualified as serious. Response criteria were qualified as recommended by the international working group for MDS. One patient (3%) achieved a major erythroid response resulting in transfusion independence throughout the study. He became transfusion dependent again within one month after study termination. 4 patients (14%) achieved a minor erythroid response with reduction of >50% of transfusion needs. No patient had a cytogenetic response. Responders did not show a reduction in del(5q) as determined in interphase fluorescence in-situ hybridization. There was no significant improvement in quality of life in responding patients as measured by the EORTC quality of life questionnaire. We conclude that the combination of ATRA and tocopherol-α is not recommended for the treatment of del(5q) MDS.