Effects of recombinant human interleukin-3 in patients with myelodysplastic syndromes

Abstract

In a phase I-II study, nine patients with myelodysplastic syndromes and concomitant severe transfusion-dependent cytopenias were treated with recombinant human interleukin-3 (rhIL-3) to improve hematopoietic function. Doses of rhIL-3 ranged from 250 micrograms/m2 to 500 micrograms/m2 and were given as daily subcutaneous bolus injections for 15 days. Blood leucocyte counts increased 1.3- to 3.6-fold in all nine patients, including neutrophils, eosinophils, lymphocytes, basophils, and monocytes. The mean absolute neutrophil counts increased from 1,350/microL (range, 150 to 2,420) to 2,660/microL (range, 300 to 9,380) (P less than .05) immediately after the end of rhIL-3 therapy and to a maximum count of 4,096/microL (range, 350 to 10,820) (P less than .01). Platelet responses were seen in two of four profoundly thrombocytopenic patients, resulting in discontinuation of platelet transfusion. The requirements for red blood cell transfusion temporarily improved in one patient. Stimulation of plasma cells was evident by a significant increase in serum IgM and IgA levels. Mild side effects (fever, headache, local erythema, and bone pain) were observed in some patients, while transient thrombocytopenia developed in two patients. Disease progression with an increase in blast cells was seen in one patient. These results suggest that rhIL-3 is effective in stimulating hematopoiesis of all lineages in patients with myelodysplastic syndromes and may produce at least short-term hematologic improvement.

The myelodysplastic syndromes: an analysis of prognostic factors in 226 cases from a single institution

“…There are several recent therapeutic approaches aiming at clonal differentiation of abnormal stem cells with minimal toxicity and without the risk of increasing the incidence of acute leukaemia (Ganser et al, 1990;Kurzrock et al, 1991: Hogge et al, 1991Ganser & Hoelzer, 1992b;Hirst & Mufti, 1993). The haemopoietic growth factors (granulocytemacrophage colony-stimulating factor, granulocyte colony-stimulating factor, interleukin-3 and erythropoietin) seem the most promising.…”

Changes in erythroid progenitor cell and accessory cell compartments in patients with myelodysplastic syndromes during treatment with all‐trans retinoic acid and haemopoietic growth factors

“…Cytokine secretion from LPS-stimulated monoc@s Increased amounts of inhibitory cytokines, especially TNFa, appear to be responsible for progressive anaemia in MDS (Verhoef et al, 1992). In addition, the induction of secondary cytokines with inhibitory activity seems to account for lack of platelet increase after treatment with interleukin-3 (Ganser et al, 1993b;Seipelt et al, 1993). Since ATRA has a pronounced effect on monocytes/macrophages (Tachibana et al, 1984;Turpin et al, 1990), the priming effect of ATRA and growth factor therapy on monocytes was analysed by measuring the mean LPS-inducible cytokine secretion of ILlP, IL-6, IL-8 and TNFa from peripheral blood monocytes during the course of study 1 in eight patients (patients 2.…”

Effects of myeloid cell growth factors on alkaline phosphatase, myeloperoxidase, defensin and granulocyte colony‐stimulating factor receptor mRNA expression in haemopoietic cells of normal individuals and myeloid disorders

“…Among them, G-CSF is well known for its neutrophil-specific activity, whereas both GM-CSF and IL-3 are also known to stimulate other bone marrow cells, including megakaryocytes and erythroid cells (Clark & Kamen, 1987;Metcalf, 1989). These growth factors have already been demonstrated to be useful for cyclic neutropenia (Hammond et al, 1989), congenital agranulocytosis (Bonilla et al, 1989), aplastic anaemia (Antin et al, 1988), MDS (Vadhan-Raj et al, 1987;Kobayashi et al, 1989;Ganser et al, 1990Ganser et al, , 1992Verhoef & Boogaerts, 1991;Nand et al, 1994) and acute myelogenous leukaemia (AML) (Teshima et al, 1989;Bettelheim et al, 1991), especially for the purpose of increasing and activating neutrophils. However, the exact roles of these three growth factors on neutrophil activation have not yet been fully elucidated.…”