title: Long-term follow-up results of the combination of topotecan and cytarabine and other intensive chemotherapy regimens in myelodysplastic syndrome.
abstract: BACKGROUND
  Progressive or higher-risk myelodysplastic syndrome (MDS) is often treated with intensive chemotherapy regimens used for acute myelogenous leukemia (AML). Patients with MDS are often older and may have contraindications to anthracycline-based regimens. Topotecan-cytarabine regimens have shown encouraging results in higher-risk MDS. The aim of this study was to analyze the long-term results with topotecan-cytarabine versus other intensive chemotherapy regimens in higher-risk MDS.
  
  
  METHODS
  Five hundred ten patients with higher-risk MDS treated with intensive chemotherapy were reviewed. Their median age was 63 years; 82% had intermediate 2 or high-risk MDS; 32% had secondary MDS; 40% had chromosome 5 or 7 abnormalities. Therapy was: topotecan-cytarabine in 77; idarubicin-cytarabine regimens in 270; topotecan-cytarabine and cyclophosphamide in 67; fludarabine-cytarabine in 96. Univariate and multivariate analyses were conducted to evaluate the independent associations of different variables, and most important, the treatment regimen, with complete response, induction mortality, and survival.
  
  
  RESULTS
  The overall complete response (CR) rate was 55%, induction mortality 17%, and 5-year survival rate 8%. The 5-year survival rate was 11% for patients younger than 65 years old and 17% for patients with a normal karyotype. Among 82 patients younger than 65 years with a normal karyotype, the CR rate was 67%, 5-year survival rate 27%, and 5-year CR duration rate 33%. Topotecan-cytarabine regimens were equivalent to idarubicin-cytarabine regimens in relation to CR rates and survival rates, but were associated with a lower induction mortality. Multivariate analysis confirmed that treatment regimens were not associated with independent significant differences in CR rates or survival. However, topotecan-cytarabine regimens were still selected to be associated with lower induction mortality rates.
  
  
  CONCLUSIONS
  This analysis suggests that topotecan-cytarabine regimens are equally effective to other AML regimens in higher-risk MDS and may be less toxic. Topotecan-cytarabine may be considered a reasonable alternative to idarubicin-cytarabine in higher-risk MDS, particularly in older patients with contraindications to anthracyclines.
authors.affiliation: Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77230, USA. hkantarj@mdanderson.org
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Miloslav
authors.initials: M
authors.lastname: Beran
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.forename: Jianqin
authors.initials: J
authors.lastname: Shan
authors.forename: William
authors.initials: W
authors.lastname: Plunkett
authors.forename: Michael
authors.initials: M
authors.lastname: Keating
authors.forename: Elihu
authors.initials: E
authors.lastname: Estey
mesh_terms: D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D019772:Topotecan / Q000008:administration & dosage; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D003561:Cytarabine; D019772:Topotecan; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D015255:Idarubicin