Ps. Frenette et al., GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) PRIMING IN THE TREATMENT OF ELDERLY PATIENTS WITH ACUTE MYELOGENOUS LEUKEMIA, American journal of hematology, 49(1), 1995, pp. 48-55
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.