title: Efficacy and feasibility of cyclophosphamide combined with intermediate- dose or high-dose cytarabine for relapsed and refractory acute myeloid leukemia (AML).
abstract: BACKGROUND
  Approximately, 70 % of adult patients with de novo acute myeloid leukemia (AML) achieve a complete remission (CR) while 10-20 % of AML are refractory to induction chemotherapy. Furthermore, a significant proportion of AML patients in CR will relapse during or after consolidation treatment. There is no evidence for a standard salvage regimen and most centers use a combination of an anthracycline and cytarabine (AraC). The aim of this study was to investigate the impact of two age-adjusted regimens containing AraC and cyclophosphamide applied for the treatment of relapsed or refractory AML.
  
  
  METHODS
  We retrospectively analyzed 60 patients (24 male, 36 female; median age 56 years) with relapsed or refractory AML who were treated with a combination of AraC and cyclophosphamide monocentrically between October 2000 and January 2013. Two different protocols containing either high-dose (hAC) or intermediate-dose cytarabin (iAC) have been applied dependent on age and performance status.
  
  
  RESULTS
  We demonstrate an overall response rate (CR + PR) induced by hAC and iAC of 56.7 %. Importantly, a complete remission rate (CR + CRp) of 52.2 % was found in patients who received the hAC regimen while only 8.8 % of patients achieved a CR following the iAC protocol (p < 0.001). The rate of refractory disease was 26.1 and 47.1 %, respectively. High-risk cytogenetics, i.e., a complex aberrant or monosomal karyotype had no effect on achievement of CR after hAC. In addition, there was no impact of activating FLT3 mutations on response to treatment according to the hAC regimen. In the cohort of patients treated with the iAC protocol, treatment-related mortality of 11.8 % within 60 days was observed but none of the patients who received the hAC regimen died within the first 2 months following chemotherapy. The toxicity profile was acceptable at both cytarabine dose levels. Importantly, 19 patients (82.6 %) of the hAC cohort underwent allogeneic hematopoietic stem cell transplantation (HSCT) as consecutive treatment.
  
  
  CONCLUSIONS
  The hAC regimen represents a promising therapeutic approach to induce a second CR in younger patients with relapsed or refractory AML prior to HSCT without using anthracyclines.
authors.affiliation: Abteilung Hämatologie und Internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Schnetzke
authors.forename: Peter
authors.initials: P
authors.lastname: Fix
authors.forename: Baerbel
authors.initials: B
authors.lastname: Spies-Weisshart
authors.forename: Karin
authors.initials: K
authors.lastname: Schrenk
authors.forename: Anita
authors.initials: A
authors.lastname: Glaser
authors.forename: Hans-Joerg
authors.initials: HJ
authors.lastname: Fricke
authors.forename: Paul
authors.initials: P
authors.lastname: La Rosée
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Sebastian
authors.initials: S
authors.lastname: Scholl
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012189:Retrospective Studies; D016879:Salvage Therapy; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D003561:Cytarabine; D003520:Cyclophosphamide; C497970:FLT3 protein, human; D019009:Proto-Oncogene Proteins c-kit; D051941:fms-Like Tyrosine Kinase 3
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