Megakaryocytic growth in patients with refractory anemia is suppressed by treatment with interferon alpha

IFN alpha alone or in combination with retinoids or haematopoietic growth f actors has been used to treat patients with early MDS because of its proper ties as a differentiation inducing agent. We investigated whether treatment of patients with refractory anemia (RA) with IFN alpha (1.5x10(6) IU twice a week) and intermittent all-trans retinoic acid (ATRA, 25 mg/m(2)/d) infl uences in-vitro megakaryocytic (MK) proliferation and differentiation stimu lated by PEG-rHuMGDF. Low density non-adherent bone marrow (BM) cells from 8 patients with RA were assayed prior to any treatment other than supportiv e and after a period of 6 months of treatment. MK development was assayed i n suspension cultures in the presence of PEG-rHuMGDF and SCF for 7 d using morphological criteria and flowcytometric analysis of CD42b (GP1b) positive cells. BM-cells from 10 healthy individuals served as control. Following s timulation with PEG-rHuMGDF 23+/-7% and 16+/-4% of control cells were CD42b positive after 5 and 7 d of cultures, respectively. In cultures of cells f rom MDS patients prior to treatment 8+/-2% and 7+/-3% of cells were CD42bon days 5 and 7. In the course of IFN alpha treatment cultures of all BM sa mples from these MDS patients revealed a significant reduction of MK precur sor cells (3+/-2% CD42b+, p=0.03 and 0.04). In conclusion, treatment with I FN alpha and ATRA did not result in improved megakaryocytopoiesis as assess ed by in-vitro cultures. On the contrary, low-dose IFN alpha appears to sup press cell proliferation as well as MK development.