Recombinant human erythropoietin for the treatment of anemia in the myelodysplastic syndromes: A clinical and erythrokinetic assessment
- 28 Downloads
The clinical and ferrokinetic effects of escalating doses of subcutaneously administered recombinant human erythropoietin (rh-EPO) were studied in ten patients with myelodysplastic syndromes and severe transfusion-dependent anemia. Red blood cell transfusion requirements diminished in four patients, and one of the patients eventually became transfusion independent with an EPO-induced rise of Hb from 7.7 g/dl to 12.3 g/dl. Endogenous serum levels of EPO were significantly increased in all patients (100–5700 mU/ml), but three of four responders had a relatively low baseline level. The effective red cell iron turnover (RCIT) improved in two responding patients and even normalized in one patient. This increase in RCIT was accompanied with a decline in the ineffective red cell iron turnover (IIT). The other responding patients had a relatively preserved RCIT before EPO treatment. EPO therapy further increased the fraction of IIT in the latter patients. Red cell survival time did not increase during EPO therapy, even in the responding patients. One transient and one maintained increase in platelet count were observed. Disease progression with a sustained increase in blast cells in one patient and a transient elevation of blasts in another patient was seen. No other side effects of EPO therapy were observed. These results suggest that anemic MDS patients with low serum EPO levels and relatively spared effective erythropoiesis as measured by ferrokinetic studies may be the best candidates for treatment with recombinant human EPO.
Key wordsMyelodysplastic syndrome rh-Erythropoietin Ferrokinetic effects
Unable to display preview. Download preview PDF.
- 16.Hirashima K, Bessho M, Susaki L, Miyazawa K, Nagashima M (1989) Improvement of anaemia by intravenous injection of recombinant erythropoietin in patients with myelodysplastic syndrome and aplastic anaemia. Exp Haematol 17: 385Google Scholar
- 17.International Committee for Standardization in Haematology (1971) Recommended methods for radioisotope red cell survival. Blood 38: 378–386Google Scholar
- 23.Mitjavila MT, Villeval JL, Cramer P, Henri A, Gasson J, Krystal G, Tulliez M, Berger R, Breton-Gorius J, Vainchenker W (1987) Effects of granulocyte-macrophage colony-stimulating factor and erythropoietin on leukemic erythroid colony formation in human early erythroblastic leukemias. Blood 70: 965–973PubMedGoogle Scholar
- 29.Roodman GD, Bird A, Hutzler D, Montgomery W (1987) Tumor necrosis factor-alpha and haematopoietic progenitors: effects of tumor necrosis factor on the growth of erythroid progenitors CFU-E and BFU-E and the haematopoietic cell lines K 562, HL 60, and HEL cells. Exp Haematol 15: 928Google Scholar
- 31.Stebler C, Tichelli A, Dazzi H, Gratwohl A, Nissen C, Speck B (1990) High-dose recombinant human erythropoietin for treatment of anemia in myelodysplastic syndromes and paroxysmal nocturnal hemoglobinuria: a pilot study. Exp Haematol 18: 1204–1208Google Scholar
- 32.Urabe A, Kitamura T, Takaku F (1988) Clinical application of erythropoietin. Acta Haematol (Japonica) 51: 1355–1359Google Scholar
- 33.Vadhan-Raj S, Hittelman WN, Lepe-Zuniga JL, Gutterman JU, Broxmeyer HE (1990) Regulation of endogenous erythropoietin levels in anemia associated with myelodysplastic syndromes. N Engl J Med 75: 1749–1750Google Scholar
- 35.Witte T, Zwaan F, Hermans J, Vernant J, Kolb H, Vossen J, Lönqvist B, Beelen D, Ferrant A, Gmur J, Liu Yin J, Troussard X, Cahn J, Van Lint M, Gratwohl A (1990) Allogeneic bone marrow transplantation for secondary leukaemia and myelo-dysplastic syndrome: a survey by the Leukaemia Working Party of the European Bone Marrow Transplantation Group (EBMTG). Br J Haematol 74: 151–155PubMedGoogle Scholar