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  • Title: Granulocyte-macrophage colony stimulating factor (GM-CSF) priming in the treatment of elderly patients with acute myelogenous leukemia.
    Author: Frenette PS, Desforges JF, Schenkein DP, Rabson A, Slapack CA, Miller KB.
    Journal: Am J Hematol; 1995 May; 49(1):48-55. PubMed ID: 7741138.
    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.
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