title: French "real life" experience of clofarabine in children with refractory or relapsed acute lymphoblastic leukaemia.
abstract: BACKGROUND
  Clofarabine alone or in combination with cyclophosphamide and etoposide has shown a good efficacy and a tolerable toxicity profile in previous studies of children with relapsed or refractory leukaemia. This report describes a retrospective study of 38 French patients who received clofarabine as a monotherapy or in combination for relapsed or refractory acute lymphoblastic leukaemia (ALL) outside of clinical trials after marketing authorization.
  
  
  METHODS
  We retrospectively analysed data for 38 patients, up to 21 years old, attending 17 French centres. Thirty patients received clofarabine alone or in combination for a bone marrow relapse of acute lymphoblastic leukaemia (ALL) or refractory disease and eight patients for a high level of minimal residual disease (MRD). Survival and response durations were estimated by the Kaplan-Meier method.
  
  
  RESULTS
  For the 30 patients who received clofarabine for a bone marrow relapse of ALL (number of relapse, 1-3; median, 1), the overall remission rate (ORR) was 37%: eight complete remission (CR) and three complete remission without platelet recovery (CRp). Ten of the 11 responding patients subsequently underwent haematopoietic stem cell transplantation (HSCT).Only four of the eight patients who received clofarabine while in remission for a high level of MRD, showed a moderate improvement of MRD. Seven of these eight patients received HSCT and six of them were alive at the end of the study. One other patient was alive without receiving HSCT.However, clofarabine treatment was associated with a high risk of infection and hepatotoxicity. Febrile neutropenia grade ≥ 3 was reported in 79% of patients and documented infections grade ≥ 3 occurred in nine patients (24%). Hepatotoxicity grade 3 was reported in nine patients (24%). We observed four deaths related to treatment.
  
  
  CONCLUSIONS
  In our experience, the efficacy of clofarabine is poorer than previously reported. Its toxicity is high and can be life threatening. Prospective studies on clofarabine used during earlier phases of the disease may help to define how best this new drug can be exploited for childhood and adolescent ALL.
authors.affiliation: Department of Pediatric, APHP, Hôpital Antoine Béclère, Service de Pédiatrie, 157 rue de la porte de Trivaux, 92141 Clamart Cedex, France. pascale.trioche@abc.aphp.fr.
authors.forename: Pascale
authors.initials: P
authors.lastname: Trioche
authors.forename: Brigitte
authors.initials: B
authors.lastname: Nelken
authors.forename: Gérard
authors.initials: G
authors.lastname: Michel
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pellier
authors.forename: Arnaud
authors.initials: A
authors.lastname: Petit
authors.forename: Yves
authors.initials: Y
authors.lastname: Bertrand
authors.forename: Pierre
authors.initials: P
authors.lastname: Rohrlich
authors.forename: Claudine
authors.initials: C
authors.lastname: Schmitt
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sirvent
authors.forename: Patrick
authors.initials: P
authors.lastname: Boutard
authors.forename: Geneviève
authors.initials: G
authors.lastname: Margueritte
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pautard
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ducassou
authors.forename: Dominique
authors.initials: D
authors.lastname: Plantaz
authors.forename: Alain
authors.initials: A
authors.lastname: Robert
authors.forename: Caroline
authors.initials: C
authors.lastname: Thomas
authors.forename: Kristell
authors.initials: K
authors.lastname: Desseaux
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.forename: André
authors.initials: A
authors.lastname: Baruchel