LOW-DOSE ARA-C IN MYELODYSPLASTIC SYNDROMES (MDS) AND ACUTE-LEUKEMIA FOLLOWING MDS - PROPOSAL FOR A PREDICTIVE MODEL

Patients with myelodysplastic syndromes (MDS) comprise an extremely he terogenous group. There is a need for decision models both for predict ing the natural course of the disease and the outcomes of different tr eatment alternatives. In 102 consecutive patients with MDS or acute my elogenous leukemia (AML) following MDS, pre-treatment variables were s tudied in relation to the response to treatment with low-dose ara-C. T hirty patients (29%) responded with either a complete remission or a s ignificant rise in the hemoglobin level. For the remaining 71%, the tr eatment was ineffective and in some cases hazardous. The factors assoc iated with a poor response to treatment could be divided into two grou ps: one included low platelet counts and the presence of chromosomal a berrations, both signs of progressive MDS with a short survival, and t he other comprised morphological findings, indicating ineffective hemo poiesis. Patients with platelet counts > 150 x 10(9)/l had a response rate of 55%, compared to 24% in patients with subnormal platelet count s. Logistic regression identified low bone marrow cellularity, absence of ring sideroblasts and <2 chromosomal aberrations as predictors of a favourable response in patients with platelet counts < 150 x 10(9)/l . These factors and the platelet count were combined in a predictive m odel which divided patients into dime groups with different probabilit ies of response: one favourable (38% of the patients), with a response rate of >50%; a second, intermediate group (33% of the patients), wit h a response rate of 24%; and a third, unfavourable group (29% of the patients) with only 3% responses. While low-dose ara-C is an effective treatment for some patients, it is ineffective and hazardous for othe rs. We propose a model that can facilitate therapeutic decision-making in 2/3 of patients with MDS and MDS-AML by identifying diose who shou ld not be treated with low-dose ara-C as well as those with a relative ly high probability of response.