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 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.
Frenette
P S
PS
Department of Medicine, New England Medical Center, Boston, MA 02111, USA.
Desforges
J F
JF
Schenkein
D P
DP
Rabson
A
A
Slapack
C A
CA
Miller
K B
KB
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
D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006918:Hydroxyurea