The Therapeutic Effect of Recombinant Human Cytokines (GM-CSF, Interleukin-3, Erythropoietin) in Patients with Myelodysplastic Syndromes

Ganser, Arnold; Eder, Matthias; G, Geissler; Hess, U; Ottmann, O. G.; Seipelt, G.; Vogt, Hans-Rudolf; Hoelzer, Dieter

doi:10.1007/978-3-642-77074-6_37

Cited by 15 publications

(24 citation statements)

References 13 publications

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“…The molecule has an impact on the prevention of chemotherapy-induced neutropenia and in the treatment of cytopeniae associated with myelodysplastic syndrome and aplastic anemia (25,26). It would seem that IL-3 represents a novel and unique hemopoietic growth factor that, according to the results obtained-in this study, may be effective in the prevention of fetal loss in APLS.…”

Section: Discussionmentioning

confidence: 62%

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Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3.

Fishman

Falach-Vaknine²,

Zigelman³

et al. 1993

J. Clin. Invest.

135

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Antiphospholipid antibodies are strongly associated with arterial and venous thrombosis and with fetal loss. Recently an experimental model for antiphospholipid syndrome (APLS) was established in our laboratory. In this model, mice are immunized passively or actively with anticardiolipin antibodies and acquire the syndrome, which is characterized by prolonged activated partial thromboplastin time (APTT), thrombocytopenia, low fecundity rate, and fetal loss.In a normal process of pregnancy, lymphokines affect fetal implantation and development. Cytokines from the colony stimulating factor family, like GM-CSF and IL-3, were shown to be positive signals for implantation and to promote placental development and fetal growth.Given our preliminary findings of low IL-3 in mice with APLS and the efficacy of IL-3 in preventing fetal loss in a strain of mice prone to fetal resorption, our aim in the present study was to examine the effect of murine recombinant IL-3 (mrIL-3) on pregnant mice induced with experimental APLS. Mice were passively transfused to the tail vein, 24 h following mating, with anticardiolipin antibodies. The mice were divided into two groups: one group was injected intraperitoneally with mrIL-3 on days 6.5, 8.5, and 10.5 after mating, while the control group was injected with PBS. When the mice were killed on day 15 of pregnancy a 32%±4.2 resorption rate was observed in the anti-cardiolipin-immunized group, which was reduced to 4%±0.3 following treatment with mrIL-3. The thrombocytopenia associated with the experimental APLS was also corrected following lymphokine administration. IL-3 may be effective in prevention of recurrent fetal loss in APLS. (J. Clin.

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Section: Discussionmentioning

confidence: 62%

“…Human recombinant IL-3, introduced in clinical trials in the last three years, has been shown to exert minimal toxicity and side effects (25)(26)(27). The molecule has an impact on the prevention of chemotherapy-induced neutropenia and in the treatment of cytopeniae associated with myelodysplastic syndrome and aplastic anemia (25,26).…”

Section: Discussionmentioning

confidence: 99%

Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3.

Fishman

Falach-Vaknine²,

Zigelman³

et al. 1993

J. Clin. Invest.

135

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“…12 Furthermore, it may also increase erythropoiesis and megakaryopoiesis in MDS in vivo and thus exert a multilineage response. 13 Since no data were available regarding the feasibility of such an approach, the EORTC Leukemia Cooperative Group (LCG) has performed a phase I/II dose escalation study of IL-3 in combination with LD-AraC 14 as a pilot. It was shown that the combination was well tolerated and that stable responses can be achieved.…”

Section: Introductionmentioning

confidence: 99%

Low-dose cytosine arabinoside (LD-AraC) vs LD-AraC plus granulocyte/macrophage colony stimulating factor vs LD-AraC plus Interleukin-3 for myelodysplastic syndrome patients with a high risk of developing acute leukemia: final results of a randomized phase III study (06903) of the EORTC Leukemia Cooperative Group

et al. 2005

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In this randomized phase III study of the EORTC Leukemia Cooperative Group, patients with myelodysplastic syndromes (MDS) with 10-30% bone marrow blasts and hematopoietic failure were treated with low-dose cytosine arabinoside (LDAraC) (2 Â 10 mg/m 2 /day subcutaneously (s.c.) days 1-14) either alone or in combination with rhGM-CSF or interleukin-3 (IL-3) both given s.c. at a dose of 150 lg/day from day 8 to 21. A total of 180 evaluable patients with a median age of 65 years and refractory anemia with an excess of blasts (RAEB, n ¼ 107) or RAEB in transformation (RAEBt, n ¼ 73) were randomized. There were no differences among the three treatment regimens with respect to numbers of courses applied or treatment delays. Hemorrhage occurred in approximately 40% in all arms, whereas infection rates were higher in the granulocyte/macrophage colony stimulating factor (GM-CSF)-or IL3-containing arm. The overall response rate was 38.6% with no statistically significant difference among the three arms. In summary, a substantial proportion of patients had achieved relatively durable responses in all the three arms. No influence of either growth factor was detected on the grade of cytopenia. Thus, the combination of LD-AraC with GM-CSF or IL-3 cannot be recommended for routine use in a high-risk MDS population.

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“…Several studies with rhIL-3 have been reported, including studies in patients with advanced malignancies (Ganser et al, 1990a;Kurzrock et al, 1991), myelodysplastic syndromes (Ganser et al, 1990c), and aplastic anaemia (Ganser et al, 1990b). Only a few studies have reported rhIL-3 administration in patients with chemotherapy-induced myelosuppression (Kurzrock et al, 1991;Biesma et al, 1992).…”

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confidence: 99%

Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours

Dercksen

Hoekman²,

Huinink³

et al. 1993

Br J Cancer

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Summary Two clinical studies were undertaken to study the toxicity profile and effects of interleukin-3 (rhIL-3) on chemotherapy-induced myelosuppression.Fifteen patients with recurrent ovarian carcinoma were treated with high dose carboplatin (800 mg m-2). All patients received 5.0 fig/kg/d rhIL-3 subcutaneously but timing and duration of rhIL-3 treatment differed.Constitutional symptoms were the major toxicity and in addition to the carboplatin-induced nausea and vomiting the combination was poorly tolerated. In 5/15 patients receiving high dose carboplatin rhIL-3 administration was discontinued due to nephrotoxicity (2 x ), hypotension, severe malaise and bone pain. In this study, rhIL-3 ameliorated chemotherapy-induced neutropenia as well as thrombocytopenia and reduced the requirement for platelet transfusions in the second cycle of chemotherapy. However, rhlL-3 failed to prevent cumulative platelet toxicity. In the second study 12 patients with small cell undifferentiated cancers were treated with carboplatin, etoposide and ifosfamide. Three dose levels of rhIL-3 were explored (0.125, 5.0 and 7.5 pg/kg/d). In this study, toxicity of the treatment was mild, however, no beneficial haematologic effects of rhIL-3 could be demonstrated.In conclusion, the haematological effects of rhIL-3 were modest and dependent on the chemotherapeutic regimen, timing and duration of rhIL-3 treatment (in relation to the expected nadir). In general rhIL-3-induced toxicity was mild, but combination with high dose carboplatin could be hazardous if rhIL-3 is initiated at 24 h after the cytostatic agent.

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The Therapeutic Effect of Recombinant Human Cytokines (GM-CSF, Interleukin-3, Erythropoietin) in Patients with Myelodysplastic Syndromes

Cited by 15 publications

References 13 publications

Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3.

Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3.

Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours

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