title: Clofarabine does not negatively impact the outcomes of patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation.
abstract: We evaluated whether clofarabine-containing chemotherapy predisposed patients to hepatic toxicity (particularly venoocclusive disease [VOD]) after allogeneic stem cell transplantation (allo-SCT). In the group who received clofarabine and subsequent transplantation, there were no cases of VOD, and liver toxicity was comparable to a control group who received standard acute myeloid leukemia (AML) chemotherapy. Other transplant-specific outcomes, including overall survival (OS), were also similar when compared with the control group.
  
  
  BACKGROUND
  Clofarabine is actively being investigated as a component of frontline chemotherapy for acute myeloid leukemia (AML). Hepatotoxicity is 1 of the primary adverse events associated with clofarabine and can occasionally can include severe venoocclusive disease (VOD).
  
  
  METHODS
  Many patients with AML undergo allogeneic stem cell transplantation (allo-SCT), a procedure that is also associated with hepatotoxicity. We identified AML patients undergoing allo-SCT and stratified them according to whether they received clofarabine-containing (clofarabine, idarubicin, and cytarabine [CIA]) or non-clofarabine-containing cytarabine-based induction/consolidation chemotherapy (idarubicin and cytarabine [ara-C] [IA]). We compared both groups for differences in posttransplantation hepatotoxicity, VOD, and other transplantation outcomes. Forty-two patients were identified (20 receiving CIA and 22 receiving IA). Patient and transplant characteristics were similar. All patients receiving clofarabine-based treatment received CIA within 2.5 months of their allo-SCT.
  
  
  RESULTS
  There was no difference in the incidence of VOD in the 30 days after transplantation (0 CIA, 1 IA; P = 1.0). Rates of grade 3/4 hepatotoxicity also did not differ between groups. Acute graft-versus-host disease (GVHD), early relapse, and survival were also not significantly different.
  
  
  CONCLUSIONS
  We conclude that clofarabine-containing chemotherapy does not adversely impact the outcome of allo-SCT. Specifically, it does not predispose patients to an increased risk of hepatotoxicity, VOD, GVHD, or relapse.
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, Houston, TX 77005, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Mathisen
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintás-Cardama
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001087:Arabinonucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077866:Clofarabine; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D008107:Liver Diseases / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D000077866:Clofarabine