Darbepoetin 500 mcg Q3W, Alone or in Combination with Peg-Filgrastim, in Low/Int1 IPSS Risk Myelodysplastic Syndromes Unresponsive to Recombinant Erythropoietin

التفاصيل البيبلوغرافية
العنوان: Darbepoetin 500 mcg Q3W, Alone or in Combination with Peg-Filgrastim, in Low/Int1 IPSS Risk Myelodysplastic Syndromes Unresponsive to Recombinant Erythropoietin
المؤلفون: Maria Carmen Martorelli, Roberto Guariglia, Fiorella D'Auria, Laura Campioni, Oreste Villani, Carla Papa, Francesco Lanza, Rosa Lerose, Pellegrino Musto, Giuseppe Pietrantuono
المصدر: Blood. 110:4606-4606
بيانات النشر: American Society of Hematology, 2007.
سنة النشر: 2007
مصطلحات موضوعية: medicine.medical_specialty, Myeloid, business.industry, Myelodysplastic syndromes, Immunology, Alpha (ethology), Cell Biology, Hematology, Neutropenia, medicine.disease, Biochemistry, Gastroenterology, Granulocyte colony-stimulating factor, medicine.anatomical_structure, Internal medicine, Concomitant, medicine, Erythropoiesis, Adverse effect, business
الوصف: Darbepoetin (DPO), a long acting erythropoiesis stimulating protein, is effective in inducing erythroid responses in 40–71% of anemic patients with myelodysplastic syndromes (MDS) when given at fixed doses of 150–300 mcg once-a-week. Of interest, some of these responses have been reported in MDS patients previously treated with (and occasionally unresponsive to) recombinant erythropoietin (r-EPO). We aimed to explore, on a compassionate basis, the effects of a higher DPO dose, administered with longer intervals, specifically in this last setting of patients. A single s.c. injection of DPO at the dose of 500 mcg s.c. was given every 3 weeks (Q3W) in fifteen anemic MDS patients, who had a history of an unsuccessful prior treatment with alpha or beta r-EPO (total weekly doses of r-EPO received: 30.000–80.000 U, for at least 8 weeks), both primary resistant or with loss of efficacy after an initial response. Informed consent was obtained in all cases. Nine patients were male, six female; mean age was 71 years (range 62–82). According to WHO classification, there were 5 RA, 3 RARS, 6 RCMD and 1 RCMD-RS. IPSS score was low in 6 patients and intermediate-1 in the remaining 9 subjects. Baseline Hb levels ranged from 6.2 to 9.1 g/dl, twelve patients being transfusion-dependent. All patients were treated with at least 3 DPO doses (nine weeks of therapy) and were evaluable for short term response and safety. No relevant adverse effect attributable to DPO was recorded. According to recently revised IWG criteria, three patients (20%) achieved an erythroid response. Transfusion-independence was obtained in one of two transfusion-dependent responders. All responses occurred after 2 doses of DPO in patients with baseline endogenous EPO below 200 miu/ml, two of whom previously treated with r-EPO 10.000 U s.c. t.i.w, while one had received 40.000 U s.c. b.i.w. Erythroid responses were maintained prolonging intervals between two DPO administrations up to 6 weeks. Based on the previously described possible synergism between r-EPO and myeloid growth-factors in MDS and to the concomitant presence of symptomatic neutropenia, five patients non-responding to DPO alone received Peg-filgrastim, a novel, pegylated form of granulocyte-colony stimulating factor (G-CSF) with prolonged terminal half-life, at the dose of 6 mg s.c. every 3 weeks, in combination with DPO, for an additional period of 9 weeks. The treatment was well tolerated, but no improvement in Hb levels or reduction in transfusional support was observed. A significant increase in peripheral blood WBC count occurred in all patients treated with Peg-filgrastim. In this preliminary experience, DPO given at the fixed dose of 500 mcg Q3W was effective in some anemic MDS patients considered unresponsive to r-EPO. However, it should be taken into account the fact that at least two of responders had probably previously received r-EPO at sub-optimal doses (less than 40.000 U per week). The adjunct of Peg-filgrastim in this setting of patients resulted in an improvement of neutropenia, without effects on Hb levels.
تدمد: 1528-0020
0006-4971
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::80b6d02e5eb2a687a1d098dccc32d43c
https://doi.org/10.1182/blood.v110.11.4606.4606
رقم الأكسشن: edsair.doi...........80b6d02e5eb2a687a1d098dccc32d43c
قاعدة البيانات: OpenAIRE