Prognostic factors in adult de novo myelodysplastic syndromes treated by intensive chemotherapy

We treated 47 adult patients with de novo myelodysplastic syndrome (MDS) by an anthracycline-AraC regimen. Median age was 54, and M/F 1.3. At diagnosis, 26 patients had refractory anaemia with an excess of blasts in transformation (RAEB-T) three had refractory anaemia (RA), 11 had refractory anaemia with excessive blasts (RAEB) and seven had chronic myelomonocytic leukaemia (CMML). Treatment was started within 3 months of diagnosis in 30 patients, and after more than 3 months in the 17 remaining patients. At the onset of treatment, 16 patients had progressed to acute myeloid leukaemia (AML). Twenty-two patients (47%) reached complete remission (CR), 10 (21%) had hypoplastic death and 15 (32%) had resistant disease. Median actuarial disease-free interval was 11 months. Median actuarial survival was 14 months from diagnosis and 10 months from the onset of treatment. A significantly higher CR rate was found in patients with RAEB-T at diagnosis (69% v 19% in patients with other FAB subtypes: P = 0.008), and in patients treated within 3 months of diagnosis. Using multivariate analysis, RAEB-T at diagnosis emerged as the most powerful prognostic factor of CR achievement. Karyotype was the only significant prognostic factor of disease-free interval, with a median of 16.5 months in patients with normal karyotype versus 4 months in patients with normal findings (P = 0.018). A subgroup of 15 patients with RAEB-T at diagnosis and normal karyotype, who had a CR rate of 80% and a median actuarial disease-free interval of 18 months, could be identified. Our results confirm that, overall, intensive chemotherapy has limited efficacy in MDS, especially when compared with allogeneic bone marrow transplantation (BMT). Relatively favourable results were obtained in our patients with RAEB-T at diagnosis, however, particularly those with normal karyotype. In that subgroup, intensive chemotherapy may be recommended, especially before BMT, as a high risk of relapse after BMT in patients with RAEB-T allografted as first line therapy has been reported.