title: Timed-sequential chemotherapy with concomitant granulocyte colony-stimulating factor for newly diagnosed de novo acute myelogenous leukemia.
abstract: EMA, consisting of etoposide, mitoxantrone, and cytarabine, is a timed-sequential chemotherapy (TSC) regimen and an efficacious option for induction treatment of acute myelogenous leukemia (AML). Hematopoietic growth factors (HGFs) have been shown to recruit leukemic blasts into cell cycle. We postulated the addition of granulocyte colony-stimulating factor (G-CSF) to EMA (EMA-G) might enhance treatment efficacy. EMA-G consisted of mitoxantrone on days 1-3, cytarabine on days 1-3 and 8-10, etoposide on days 8-10, and G-CSF from day 4 until absolute neutrophil count (ANC) >500/microl. In total, 28 patients were enrolled. All patients had newly diagnosed de novo AML. The median age was 42 years. Of the 27 patients with cytogenetic analysis, six had favorable karyotype, 18 intermediate karyotype, and three unfavorable karyotype. The median follow-up was 37.5 months. The median time for both ANC recovery and last platelet transfusion was 26 days. The toxicities associated with this regimen were no more than those expected with the standard chemotherapy. In all, 24 (86%) patients achieved complete remission (CR), three (11%) patients had no response, and one patient died within 24 h of induction therapy before response could be evaluated. Of the 24 patients who achieved CR, 22 received high-dose cytosine arabinoside and two received allogeneic bone marrow transplant as initial postremission therapy. For the whole cohort, the estimated 3-year survival rate was 67%. The median relapse-free survival was 30.5 months. We conclude that EMA-G regimen is a safe regimen and administration of G-CSF during and after induction treatment is not associated with prolongation of marrow aplasia or acceleration of leukemia relapse. It is efficacious for induction therapy for newly diagnosed de novo AML. A high CR rate can be achieved with only one course of this chemotherapy.
authors.affiliation: Department of Hematology and Medical Oncology, 9500 Euclid Avenue, R35, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: X-Y
authors.initials: XY
authors.lastname: He
authors.forename: B
authors.initials: B
authors.lastname: Pohlman
authors.forename: A
authors.initials: A
authors.lastname: Lichtin
authors.forename: L
authors.initials: L
authors.lastname: Rybicki
authors.forename: M
authors.initials: M
authors.lastname: Kalaycio
mesh_terms: D000208:Acute Disease; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; 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* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D010166:Palliative Care; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D008942:Mitoxantrone