PMID- 2823014 OWN - NLM STAT- MEDLINE DCOM- 19871207 LR - 20131121 IS - 0887-6924 (Print) IS - 0887-6924 (Linking) VI - 1 IP - 2 DP - 1987 Feb TI - A trial of recombinant alpha 2 interferon in the myelodysplastic syndrome: II. Characterization and response of granulocyte and platelet dysfunction. PG - 111-5 AB - 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. FAU - Elias, L AU - Elias L AD - Cancer Center, University of New Mexico School of Medicine, Albuquerque. FAU - Van Epps, D E AU - Van Epps DE FAU - Smith, K J AU - Smith KJ FAU - Savage, B AU - Savage B LA - eng GR - 3 MO1 RR00997/RR/NCRR NIH HHS/United States GR - HL24336/HL/NHLBI NIH HHS/United States GR - HL31950/HL/NHLBI NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Leukemia JT - Leukemia JID - 8704895 RN - 0 (Interferon Type I) RN - 0 (Receptors, Formyl Peptide) RN - 0 (Receptors, Immunologic) RN - 11062-77-4 (Superoxides) RN - 61D2G4IYVH (Adenosine Diphosphate) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - EC 1.11.1.7 (Peroxidase) SB - IM MH - Adenosine Diphosphate/blood MH - Adenosine Triphosphate/blood MH - Blood Platelets/*physiology MH - Chemotaxis, Leukocyte MH - Granulocytes/*physiology MH - Humans MH - Interferon Type I/*therapeutic use MH - Myelodysplastic Syndromes/physiopathology/*therapy MH - Peroxidase/metabolism MH - Platelet Aggregation MH - Prospective Studies MH - Receptors, Formyl Peptide MH - Receptors, Immunologic/physiology MH - Superoxides/metabolism EDAT- 1987/02/01 00:00 MHDA- 1987/02/01 00:01 CRDT- 1987/02/01 00:00 PHST- 1987/02/01 00:00 [pubmed] PHST- 1987/02/01 00:01 [medline] PHST- 1987/02/01 00:00 [entrez] PST - ppublish SO - Leukemia. 1987 Feb;1(2):111-5.