Clofarabine, cyclophosphamide and etoposide as single-course re-induction therapy for children with refractory/multiple relapsed acute lymphoblastic leukaemia

Br J Haematol. 2009 Nov;147(3):371-8. doi: 10.1111/j.1365-2141.2009.07882.x. Epub 2009 Aug 29.

Abstract

The safety and efficacy of the combination clofarabine/cyclophosphamide/etoposide were evaluated in children with advanced acute lymphoblastic leukaemia (ALL). The study enrolled 25 paediatric patients (median age 12.5 years) with either refractory (n = 17; 68%) or multiple relapsed (n = 8; 32%) ALL to receive clofarabine 40 mg/m(2), cyclophosphamide 400 mg/m(2) and etoposide 150 mg/m(2), daily for 5 consecutive days. No patient died from treatment-related complications. The most common adverse events were febrile neutropenia, mucositis and reversible liver toxicity; no case of liver veno-occlusive disease was reported. The overall remission rate was 56%: 13 patients (52%) achieved complete remission (CR) and one (4%) CR without platelet recovery (CRp). In seven of the 13 (54%) patients achieving CR, remissions were of sufficient duration to allow patients to receive allogeneic haematopoietic stem cell transplantation. The probability of CR/CRp was greater in the 17 patients with B cell precursor ALL than in the eight with T-ALL (76% vs. 12%, respectively, P < 0.01). The 18-month overall survival probability was 39% and 0% in patients who did or did not respond to the treatment, respectively (P < 0.01). These data suggest that the clofarabine/cyclophosphamide/etoposide regimen is well tolerated and can induce clinical response in a relevant proportion of children with refractory/multiple relapsed ALL.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine Nucleotides / administration & dosage
  • Adenine Nucleotides / adverse effects
  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Arabinonucleosides / administration & dosage
  • Arabinonucleosides / adverse effects
  • Child
  • Child, Preschool
  • Clofarabine
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Infant
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Recurrence
  • Remission Induction
  • Survival Analysis
  • Treatment Outcome

Substances

  • Adenine Nucleotides
  • Arabinonucleosides
  • Etoposide
  • Clofarabine
  • Cyclophosphamide