title: Granulocyte-macrophage colony-stimulating factor (GM-CSF) priming with successive concomitant low-dose Ara-C for elderly patients with secondary/refractory acute myeloid leukemia or advanced myelodysplastic syndrome.
abstract: Patients with advanced MDS and secondary AML respond poorly to chemotherapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) can stimulate proliferation of leukemic blasts and sensitize these cells to the cytotoxic effects of S-phase-specific drugs. This is the first report of safety and efficacy of GM-CSF prior to and during cytarabine in a low-dose, intermittent regimen for elderly patients with poor risk acute myelogenous leukemia or myelodysplastic syndrome. Twenty patients, age 68 to 86 years, each received 250 microg/m2 of GM-CSF (Sargramostatin; Immunex, Seattle, WA, USA) subcutaneously (s.c.) or intravenously (i.v.) for 3 days followed by GM-CSF at the same dose and cytarabine 100 mg/m2 i.v. for 3 days. GM-CSF and cytarabine were both administered for 3 days during weeks 2 and 3 followed by a 3-week rest period. Rates of CR and PR were 20% and 40%, respectively. These included clinically significant resolution of cytopenias and transfusion requirements. Many of the responding patients had been heavily pretreated prior to enrollment. One- and 2-year survival estimates are 44% and 19%, respectively. Myelosuppression was the most significant toxicity. Our findings suggest that this novel combination of GM-CSF with sequential and concomitant low-dose cytarabine can benefit patients with poor risk myeloid malignancies.
authors.affiliation: Division of Hematology and Oncology, University of Massachusetts Medical Center, Worcester, MA, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Rossi
authors.forename: J
authors.initials: J
authors.lastname: O'Donnell
authors.forename: F
authors.initials: F
authors.lastname: Sarcinelli
authors.forename: F M
authors.initials: FM
authors.lastname: Stewart
authors.forename: P J
authors.initials: PJ
authors.lastname: Quesenberry
authors.forename: P S
authors.initials: PS
authors.lastname: Becker
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor