A trial of recombinant alpha 2 interferon in the myelodysplastic syndrome: II. Characterization and response of granulocyte and platelet dysfunction

Because qualitative neutrophil and platelet dysfunction is an important concomitant of the myelodysplastic syndrome, functional studies were performed prospectively of cells from eight patients with myelodysplastic syndrome undergoing treatment with recombinant alpha 2 interferon. Neutrophil studies performed included myeloperoxidase release and superoxide anion generation, measured spectrophotometrically, in response to stimulation by phorbol-12-myristate-13-acetate, opsonized zymosan, and the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP), respectively. The most consistently abnormal of these tests was the fMLP-stimulated superoxide anion generation, which was low in six of seven patients tested. Mean results with this test were significantly lower than controls (mean +/- SD = 5.11 +/- 2.41 nmol/10(6) patient cells vs. 10.14 +/- 3.02 with normal cells, p less than 0.001). No significant change was noted following 2 or 8 weeks of interferon therapy. Because of the severe thrombocytopenia prevalent in myelodysplastic syndrome, fewer platelet studies were feasible. One patient, however, exhibited normal platelet numbers but markedly decreased aggregation in response to arachidonic acid, epinephrine, and collagen. After 4 weeks of treatment, this patient's platelet aggregation was noted to be normal. Platelets from two patients were purified by gel filtration, and the ATP/ADP ratios were determined by HPLC. Pretreatment ATP/ADP ratio of one patient was 4.85 (normal = 1.85 +/- 0.28) which declined to 3.27 on treatment and then returned to 4.80 following a 14-day period off treatment. Another patient, also with elevated ATP/ADP, exhibited a smaller decline during a treatment cycle. From these studies it was concluded that fMLP-stimulated superoxide generation may be a sensitive marker for neutrophil dysfunction in the myelodysplastic syndrome. No evidence was found for improvement of neutrophil dysfunction following alpha 2 interferon treatment. alpha 2 interferon, however, may sometimes have beneficial effects upon platelet dysfunction.