title: Phase 2 study of low-dose clofarabine plus cytarabine for patients with higher-risk myelodysplastic syndrome who have relapsed or are refractory to hypomethylating agents.
abstract: BACKGROUND
  The outcome of patients with higher-risk myelodysplastic syndromes (MDS) after hypomethylating agent (HMA) failure is poor. This study evaluated the safety and activity of a combination of low-dose clofarabine and cytarabine for these patients.
  
  
  METHODS
  Seventy patients with higher-risk MDS who had no response, progressed, or relapsed after at least 4 cycles of HMA therapy were treated.
  
  
  RESULTS
  The median age was 72 years. Thirty-nine percent of the patients had high-risk disease according to the International Prognostic Scoring System, and 50% of the patients had poor-risk cytogenetics. Twenty-three percent of the patients had therapy-related MDS. The median number of prior cycles of HMA was 6 (range, 4-45). The overall response rate was 44%. The 6-week mortality rate was 9%. Grade 3 and higher nonhematologic toxicities were rare, but infections occurred in 52% of the patients, and fever of unknown origin occurred in 33%. The median overall survival (OS) was 10 months (95% confidence interval, 1-37 months). Thirteen percent of the patients underwent allogeneic stem cell transplantation. The responding patients had a median OS of 22 months, whereas the nonresponding patients had a median OS of 4 months. A complex karyotype was associated with worse response rates and OS.
  
  
  CONCLUSIONS
  The combination of low-dose clofarabine and cytarabine is clinically active in these patients with few treatment options. Cancer 2017;123:629-637. © 2016 American Cancer Society.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Koji
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Tapan
authors.initials: T
authors.lastname: Kadia
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Naval
authors.initials: N
authors.lastname: Daver
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Naveen
authors.initials: N
authors.lastname: Pemmaraju
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Khoury
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bueso-Ramos
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Bohannan
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Darla
authors.initials: D
authors.lastname: Miller
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Rita
authors.initials: R
authors.lastname: Maduike
authors.affiliation: Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Chitra
authors.initials: C
authors.lastname: Hosing
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
mesh_terms: D000227:Adenine Nucleotides / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001087:Arabinonucleosides / Q000009:adverse effects*; D000077866:Clofarabine; D003561:Cytarabine / Q000009:adverse effects*; D019175:DNA Methylation / Q000187:drug effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D009363:Neoplasm Proteins; D003561:Cytarabine; D000077866:Clofarabine
keywords: clofarabine; cytarabine; hypomethylating agents; myelodysplastic syndromes; treatment failure