MORPHOLOGICAL-CHANGES AND APOPTOSIS IN BONE-MARROW FROM PATIENTS WITHMYELODYSPLASTIC SYNDROMES TREATED WITH GRANULOCYTE-CSF AND ERYTHROPOIETIN

A study of bone marrow morphology and apoptosis was undertaken in 51 p atients with myelodysplastic syndromes (MDS) treated with granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO). In 19 of t hese patients (37%), a significant improvement in the hemoglobin level was found after treatment. Apoptosis was measured using a nick-end la beling (TUNEL) technique. Patients with MDS had a significantly higher percentage of labelled (apoptotic) cells in the bone marrow compared to healthy individuals (56.3 +/- 3.8% vs. 16.2 +/- 1.4%, p = 0.0001). Patients with RAS showed a lower percentage of apoptotic cells than pa tients with RA (68.5 +/- 9% vs. 46.5 +/- 4.8%, p < 0.05), while patien ts with RAEB did not differ significantly from either RA or RAS. In th e patients who responded to treatment, the bone marrow samples display ed significant morphological changes. The percentages of erythroid pre cursors and myeloblasts were reduced after treatment, and patients who had ring sideroblasts before treatment also showed a reduction in the percentage of these cells. Total erythroid index also decreased in re sponding patients. The percentage of apoptotic cells decreased signifi cantly in responding patients (58.8 +/- 4.8% before treatment vs. 44.5 +/- 5.5% after treatment, mean reduction 18.3%, p = 0.0003), whereas no significant change was found in non-responding patients. Our result s suggest that one important mechanism behind the positive effects of treatment with G-CSF and EPO is a reduction in the degree of ineffecti ve hematopoiesis in MDS. (C) 1997 Elsevier Science Ltd.