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Titolo:
Adding growth factors or interleukin-3 to erythropoietin has limited effects on anemia of transfusion-dependent patients with myelodysplastic syndromes unresponsive to erythropoietin alone
Autore:
Musto, P; Sanpaolo, G; DArena, G; Scalzulli, PR; Matera, R; Falcone, A; Bodenizza, C; Perla, G; Carotenuto, M;
Indirizzi:
IRCCS Casa Sollievo Sofferenza, Dept Onco Hematol, Hematol Unit, I-71013 San Giovanni Rotondo, Italy IRCCS Casa Sollievo Sofferenza San Giovanni Rotondo Italy I-71013 Italy
Titolo Testata:
HAEMATOLOGICA
fascicolo: 1, volume: 86, anno: 2001,
pagine: 44 - 51
SICI:
0390-6078(200101)86:1<44:AGFOIT>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECOMBINANT-HUMAN-ERYTHROPOIETIN; COLONY-STIMULATING FACTOR; FACTOR PLUS ERYTHROPOIETIN; SERUM ERYTHROPOIETIN; REFRACTORY-ANEMIA; APLASTIC-ANEMIA; COMBINATION THERAPY; GM-CSF; CLASSIFICATION; ERYTHROCYTES;
Keywords:
erythropoietin; G-CSF; GM-CSF; interleukin-3; anemia; myelodysplastic syndromes;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
76
Recensione:
Indirizzi per estratti:
Indirizzo: Musto, P IRCCS Casa Sollievo Sofferenza, Dept Onco Hematol, Hematol Unit, I-71013 San Giovanni Rotondo, Italy IRCCS Casa Sollievo Sofferenza San Giovanni Rotondo Italy I-71013
Citazione:
P. Musto et al., "Adding growth factors or interleukin-3 to erythropoietin has limited effects on anemia of transfusion-dependent patients with myelodysplastic syndromes unresponsive to erythropoietin alone", HAEMATOLOG, 86(1), 2001, pp. 44-51

Abstract

Background and Objectives. Recombinant erythropoietin (r-EPO) induces erythroid responses in patients affected by myelodsplastic syndromes (MDS). However, the response rate declines to 10-15% in MDS with substantial transfusion needs. Both in vitro and in vivo studies have suggested that the addition of growth factors (G-CSF, GM-CSF) or interleukin-3 (IL-3) may potentiatethe effect of r-EPO on dysplastic erythropoiesis. The aim of this study was to evaluate the effects of the combination of r-EPO with G-CSF, GM-CSF orIL-3 on the anemia of heavily transfusion-dependent MDS patients, previously unresponsive to r-EPO alone. Patients and Methods. Sixty patients with transfusion-dependent MDS, already treated without significant erythroid response with r-EPO alone, were scheduled to receive, for at least 8 weeks, r-EPO subcutaneously at the dose of 300 U/kg t.i.w. in combination with G-CSF (300 mu cg s.c. t.i.w., 27 patients), or GM-CSF (300 mu cg s.c. t.i.w., 23 patients), or IL-3 (5 mu cg/kgs.c. t.i.w., 10 patients), after a two-week pre-phase during which G-CSF, GM-CSF and IL-3 were administered daily at the same dose, as single drugs. Results. Ten patients were not evaluable for erythroid response because ofrelevant side effects related to GMCSF or IL-3 administration. Overall, among 50 patients who completed the study, there were 3 erythroid responses las determined by complete abolition of red-cell transfusions): 1 (4%) in the G-CSF + r-EPO and 2 (10.5%) in the GM-CSF + r-EPO treated groups. No patient responded to the combination of r-EPO + IL-3, Ail responders had inappropriate serum levels of endogenous EPO and a relatively short disease duration. Both responders to GMCSF + r-EPO developed acute myeloid leukemia 2-9 months after the start of the combined therapy. A third elderly patient, treated with the same association, developed marrow hypoplasia. A significantincrease in leukocyte count occurred in 96% of patients who received r-EPO+ G-CSF, 78.9% of those treated with r-EPO + GM-CSF and 66% of subjects receiving r-EPO + IL-3. A significant increase in platelet count was observedin a single patient receiving r-EPO and GM-CSF, while a slight decrease inplatelet count with respect to baseline levels occurred in about 20% of patients. Interpretation and Conclusions. Our results suggest that the combination of r-EPO with G-CSF, GM-CSF or IL-3, at least at the doses and schedules employed in the present study, has limited efficacy on the anemia of heavily transfusion-dependent MDS patients previously unresponsive to r-EPO alone. However, in this setting of patients, the combination of G-CSF or GM-CSF + r-EPO may occasionally be effective in subjects with low circulating levels of serum EPO and short disease duration. (C) 2001, Ferrata Storti Foundation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 00:47:21