title: Granulocyte-macrophage colony stimulating factor (GM-CSF) priming in the treatment of elderly patients with acute myelogenous leukemia.
abstract: Standard intensive induction therapy is tolerated poorly by elderly patients with acute myeloblastic leukemia (AML). We treated 19 elderly patients with AML, including seven with a prior myelodysplastic syndrome (MDS) with a combination of low dose cytarabine, hydroxyurea, and GM-CSF. The percentage of blasts in S-phase was evaluated prior to and 24 hr after starting the GM-CSF infusion. Cell cycle analysis was performed by flow cytometry using propidium iodine staining with fluorescein isothiocyanate-conjugated monoclonal antibody to the myeloid antigen CD 33. Seven out of nineteen (37%) achieved a complete remission (CR) and six (31%) a partial remission (PR) for an overall response rate of 68% (13/19). There were three early deaths from infectious complications or organ failure. One patient died from disseminated fungal infection after attaining a PR. The medial overall survival was 9.5 months with a range of 1 to 23+ months. The projected median survival for the patients with de novo AML is greater than 23 months. The percentage of CD 33+ cells in S-phase increased from a mean of 11.6+/-2.7 (SEM) pre GM-CSF to 19.0+/-3.7 (SEM) post GM-CSF (P < 0.001). Patients with prior MDS demonstrated a greater increment (post-pre) in S-phase activity after GM-CSF administration (P = 0.02). There was a correlation between the increase in percent of CD 33+ cells in S-phase and the degree of cytoreduction as determined by the day 14 bone marrow biopsy (r = .78). The toxicity of the regimen was limited to the hematopoietic system. Sixteen out of nineteen patients (84%) and 12/13 (92%) of the responding patients had bone marrow aplasia on day 14. No patients experienced > grade 2 gastrointestinal toxicity. There was no neurologic or cardiac toxicity. These data suggest that the combination of hydroxyurea, GM-CSF, and cytarabine is an effective remission-induction regimen in elderly patients with AML.
authors.affiliation: Department of Medicine, New England Medical Center, Boston, MA 02111, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Frenette
authors.forename: J F
authors.initials: JF
authors.lastname: Desforges
authors.forename: D P
authors.initials: DP
authors.lastname: Schenkein
authors.forename: A
authors.initials: A
authors.lastname: Rabson
authors.forename: C A
authors.initials: CA
authors.lastname: Slapack
authors.forename: K B
authors.initials: KB
authors.lastname: Miller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D002453:Cell Cycle; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D015996:Survival Rate
chemical_list: D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006918:Hydroxyurea