Timed sequential chemotherapy with concomitant granulocyte colony-stimulating factor for high-risk acute myelogenous leukemia: a single arm clinical trial.
BACKGROUND
The timed-sequential chemotherapy regimen consisting of etoposide, mitoxantrone and cytarabine (EMA) is an effective therapy for relapsed or refractory acute myelogenous leukemia (AML). We postulated that granulocyte colony-stimulating factor (G-CSF) might enhance the cytotoxicity of EMA by increasing the proportion of leukemic blasts in S-phase. We added G-CSF to EMA (EMA-G) for therapy of advanced high-risk AML patients.


METHODS
High-risk AML was defined as refractory, relapsed or secondary to either an antecedent hematologic disorder or exposure to cytotoxic agents. The patients were treated with one course of EMA-G consisting of mitoxantrone and cytarabine on days 1-3, and etoposide and cytarabine on days 8-10. G-CSF was started on day 4 and continued until absolute neutrophil count recovered.


RESULTS
Thirty patients were enrolled. The median age was 51 years (range, 25-75). Seventeen (61%) patients had unfavorable cytogenetic karyotypes. Twenty (69%) patients had secondary AML. Ten (34%) had relapsed disease. Four (14%) had refractory AML. Three (10%) patients died from febrile neutropenia and sepsis. Major non-hematologic toxicity included hyperbilirubimenia, renal insufficiency, mucositis, diarrhea, nausea and vomiting, skin rash. A complete remission was achieved in 13 (46%) patients. Median overall survival was 9 months (range, 0.5-66). Median relapse-free survival (RFS) for those who had a CR was 3 months (range, 0.5-63) with RFS censored at the time of allogeneic bone marrow transplantation or peripheral stem cell transplantation for 6 of the patients.


CONCLUSIONS
EMA-G is a safe and efficacious option for induction chemotherapy in advanced, high-risk AML patients. The activity of EMA may be increased if applied in patients with less advanced disease.
He
Xing-Yue
XY
Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, Cleveland, Ohio USA. hes@ccf.org
Elson
Paul
P
Pohlman
Brad
B
Lichtin
Alan
A
Hussein
Mohamad
M
Andresen
Steve
S
Kalaycio
Matt
M
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002452:Cell Count; D003561:Cytarabine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009504:Neutrophils / Q000187:drug effects; D010976:Platelet Count; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D008942:Mitoxantrone