GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) PRIMING IN THE TREATMENT OF ELDERLY PATIENTS WITH ACUTE MYELOGENOUS LEUKEMIA

Standard intensive induction therapy is tolerated poorly by elderly pa tients with acute myeloblastic leukemia (AML). We treated 19 elderly p atients with AML, including seven with a prior myelodysplastic syndrom e (MDS) with a combination of low dose cytarabine, hydroxyurea, and GM -CSF. The percentage of blasts in S-phase was evaluated prior to and 2 4 hr after starting the GM-CSF infusion. Cell cycle analysis was perfo rmed by flow cytometry using propidium iodine staining with fluorescei n 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 o f 68% (13/19), There were three early deaths from infectious complicat ions or organ filure, One patient died from disseminated fungal infect ion after attaining a PR, The medial overall survival was 9.5 months w ith 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 pri or MDS demonstrated a greater increment (post-pre) in S-phase activity after GM-CSF administration (P = 0.02), There was a correlation betwe en 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 syst em, Sixteen out of nineteen patients (84%) and 12/13 (92%) of the resp onding patients had bone marrow aplasia on day 14, No patients experie nced >grade 2 gastrointestinal toxicity. Them was no neurologic or car diac toxicity. These data suggest that the combination of hydroxyurea, GM-CSF, and cytarabine is an effective remission-induction regimen in elderly patients with AML. (C) 1995 Wiley-Liss, Inc.