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

    loading  Checking for direct PDF access through Ovid



IFNα alone or in combination with retinoids or haematopoietic growth factors has been used to treat patients with early MDS because of its properties as a differentiation inducing agent. We investigated whether treatment of patients with refractory anemia (RA) with IFNα (1.5×106 IU twice a week) and intermittent all-trans retinoic acid (ATRA, 25 mg/m2/d) influences in-vitro megakaryocytic (MK) proliferation and differentiation stimulated by PEG-rHuMGDF. Low-density non-adherent bone marrow (BM) cells from 8 patients with RA were assayed prior to any treatment other than supportive and after a period of 6 months of treatment. MK development was assayed in 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 stimulation 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 from MDS patients prior to treatment 8±2% and 7±3% of cells were CD42b+ on days 5 and 7. In the course of IFNα treatment cultures of all BM samples from these MDS patients revealed a significant reduction of MK precursor cells (3±2% CD42b+, p=0.03 and 0.04). In conclusion, treatment with IFNα and ATRA did not result in improved megakaryocytopoiesis as assessed by in-vitro cultures. On the contrary, low-dose IFNα appears to suppress cell proliferation as well as MK development.

Related Topics

    loading  Loading Related Articles