title: Treatment with very low-dose GM-CSF in myelodysplastic syndromes with neutropenia. A report on 28 cases.
abstract: We treated 28 cases of myelodysplastic syndrome (MDS) with neutropenia by very low-dose GM-CSF (0.25 or 0.5 micrograms/kg/day). Median age was 69 years. Nine patients had RA, 18 had RAEB, and one had RARS. Eighteen patients had absolute neutrophil counts (ANC) < or = 0.5 x 10(9)/l, and ten had ANC between 0.5 and 1.0 x 10(9)/l. Ten patients had experienced > or = WHO grade II infection(s) during the preceding 3 months. Eighteen patients (64%) had a response (i.e. ANC at least doubled and > or = 1 x 10(9)/l after 1 month), including 4/8 patients treated at 0.25 mu/kg/day, and 14/20 treated at 0.5 microgram/kg/day (difference not significant). Two of the non-responders obtained a response after dose escalation to 0.5 and 1 microgram/kg/day, respectively. The only prognostic factor of response was FAB subtype (10/11 responses in patients with RA or RARS, vs. 8/17 in RAEB, p = 0.04). Patients with ANC < or = 0.5 x 10(9)/l had a 55% (10/18) response rate, which was not significantly lower than the 80% (8/10) response rate observed in patients with ANC > 0.5 x 10(9)/l. Side-effects were generally moderate, except in three patients where the drug had to be discontinued, including the only patient who progressed to AML. In responders, GM-CSF was continued during 2 to 14 months (median 6), and the response persisted in all but one case, who relapsed after 60 days of treatment. During follow-up, only one responder had > or = WHO grade II infections, as compared to five of the non-responders (of whom two had fatal infectious episodes). In conclusion, very low-dose GM-CSF can durably increase ANC in about two thirds of MDS with neutropenia. Although it remains to be shown in randomized trials that it can reduce the incidence of infections and improve survival in MDS, very low-dose GM-CSF may be an interesting approach in MDS, associated to reasonable cost.
authors.affiliation: Service des Maladies du Sang, Centre Hospitalier Universitaire, Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Rose
authors.forename: E
authors.initials: E
authors.lastname: Wattel
authors.forename: Y
authors.initials: Y
authors.lastname: Bastion
authors.forename: E
authors.initials: E
authors.lastname: Berger
authors.forename: F
authors.initials: F
authors.lastname: Bauters
authors.forename: B
authors.initials: B
authors.lastname: Coiffier
authors.forename: P
authors.initials: P
authors.lastname: Fenaux
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004890:Erythema / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications*; D009503:Neutropenia / Q000209:etiology / Q000628:therapy*; D009504:Neutrophils; D011379:Prognosis
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor