title: High dose cytarabine and mitoxantrone: an effective induction regimen for high-risk acute myeloid leukemia (AML).
abstract: Patients with high-risk AML, defined as those with advanced age, relapsed/refractory disease, unfavorable molecular and cytogenetic abnormalities, therapy-related myeloid neoplasm (t-MN) and multiple medical co-morbidities tend to respond poorly to standard cytarabine and daunorubicin induction therapy and have a poor prognosis. We performed a retrospective analysis of an alternative induction regimen using high dose cytarabine (HiDAC) and mitoxantrone (MITO) administered to 78 high-risk patients with AML at The University of Chicago from 2001 to 2008. The primary endpoints of the study were complete remission (CR) rate and death within 30 days of initiation of treatment. The median age was 63 years (range:23-85); 27% of these patients had a Charlson co-morbidity index (CCI) > 2. Forty-three (56%) patients had unfavorable cytogenetics, 28 (37%) had intermediate-risk cytogenetics and 5 (7%) had favorable cytogenetics. The CR rate was 45% and the CRi rate 10%; 7 patients (9%) died during induction. Notably, t-MN and relapsed/refractory patients had CR and induction death rates equivalent to de novo AML patients within this series. In this high risk AML population, HiDAC/MITO induction demonstrated an overall response rate of 55% with a low induction death rate of 9% and allowed 32 (41%) patients to proceed to allogeneic stem cell transplant.
authors.affiliation: Section of Hematology/Oncology, University of Chicago Hospitals, Chicago, IL 60637, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Larson
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Campbell
authors.forename: Dezheng
authors.initials: D
authors.lastname: Huo
authors.forename: Andrew
authors.initials: A
authors.lastname: Artz
authors.forename: Yanming
authors.initials: Y
authors.lastname: Zhang
authors.forename: Devika
authors.initials: D
authors.lastname: Gajria
authors.forename: Margaret
authors.initials: M
authors.lastname: Green
authors.forename: Howie
authors.initials: H
authors.lastname: Weiner
authors.forename: Christopher
authors.initials: C
authors.lastname: Daugherty
authors.forename: Olatoyosi
authors.initials: O
authors.lastname: Odenike
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Godley
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hyjek
authors.forename: Sandeep
authors.initials: S
authors.lastname: Gurbuxani
authors.forename: Michael
authors.initials: M
authors.lastname: Thirman
authors.forename: Dorothy
authors.initials: D
authors.lastname: Sipkins
authors.forename: Koen
authors.initials: K
authors.lastname: Van Besien
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Wendy
authors.initials: W
authors.lastname: Stock
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002869:Chromosome Aberrations; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007239:Infections / Q000209:etiology; D053208:Kaplan-Meier Estimate; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D009363:Neoplasm Proteins / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000188:drug therapy / Q000235:genetics / Q000601:surgery; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D012306:Risk; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins; D003561:Cytarabine; D008942:Mitoxantrone; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3