Low-dose cytosine arabinoside (LD-AraC) vs LD-AraC plus granulocyte/ macrophage colony stimulating factor vs LD-AraC plus Interleukin-3 for myelodysplastic syndrome patients with a high risk of developing acute leukemia: Final results of a randomized phase III study (06903) of the EORTC Leukemia Cooperative Group

In this randomized phase III study of the EORTC Leukemia Cooperative Group, patients with myelodysplastic syndromes (MDS) with 10-30% bone marrow blasts and hematopoietic failure were treated with low-dose cytosine arabinoside (LD-AraC) (2 x 10mg/m(2)/day subcutaneously (s.c.) days 1 - 14) either alone or in combination with rhGM-CSF or interleukin-3 (IL- 3) both given s.c. at a dose of 150 mu g/ day from day 8 to 21. A total of 180 evaluable patients with a median age of 65 years and refractory anemia with an excess of blasts (RAEB, n = 107) or RAEB in transformation (RAEBt, n = 73) were randomized. There were no differences among the three treatment regimens with respect to numbers of courses applied or treatment delays. Hemorrhage occurred in approximately 40% in all arms, whereas infection rates were higher in the granulocyte/macrophage colony stimulating factor (GM-CSF)- or IL3-containing arm. The overall response rate was 38.6% with no statistically significant difference among the three arms. In summary, a substantial proportion of patients had achieved relatively durable responses in all the three arms. No influence of either growth factor was detected on the grade of cytopenia. Thus, the combination of LD-AraC with GM-CSF or IL- 3 cannot be recommended for routine use in a high-risk MDS population.