title: Efficacy of fractionated gemtuzumab ozogamicin combined with cytarabine in advanced childhood myeloid leukaemia.
abstract: Gemtuzumab ozogamicin (GO) monotherapy is reported to yield a 20-30% response rate in advanced acute myeloid leukaemia (AML). This study examined the efficacy and tolerability of GO combined with cytarabine (GOCYT) in children with refractory/relapsed CD33(+) AML. Seventeen children received GO 3 mg/m(2) on days 1, 4 and 7 plus cytarabine 100 mg/m(2)/d for 7 d on a compassionate-use basis. Seven patients then received GO-based consolidation. At the outset of GOCYT, two patients were refractory; eight patients were in refractory first relapse; six patients had relapsed after stem cell transplantation (SCT); and one patient [del(5q) therapy-related AML (t-AML)] had not yet been treated. Mean follow-up was 17 months (8-33 months). Ten responses were obtained after GOCYT induction, including complete remission (CR) or CR without complete recovery of platelets (CRp) in six patients (35%). The responses improved in three children who received GOCYT consolidation, increasing the CR + CRp rate to 53%. SCT was subsequently performed in eight responders. Grade 3-4 adverse events consisted of haematological disorders (n = 17, 100%) and documented infections (n = 5, 29%). No cases of sinusoidal obstructive syndrome occurred. Three patients were alive at the cut-off date for this analysis, all of whom had responded to GOCYT. GOCYT combination therapy yielded a high response rate (53%) and showed acceptable toxicity in heavily pretreated children with refractory/relapsed AML. These results warrant a larger prospective study.
authors.affiliation: Hématologie Pédiatrique, Hôpital Saint-Louis, APHP, Paris, France. benoit.brethon@sls.aphp.fr
authors.forename: Benoit
authors.initials: B
authors.lastname: Brethon
authors.forename: Karima
authors.initials: K
authors.lastname: Yakouben
authors.forename: Caroline
authors.initials: C
authors.lastname: Oudot
authors.forename: Patrick
authors.initials: P
authors.lastname: Boutard
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Bruno
authors.forename: Cécile
authors.initials: C
authors.lastname: Jérome
authors.forename: Brigitte
authors.initials: B
authors.lastname: Nelken
authors.forename: Lionel
authors.initials: L
authors.lastname: de Lumley
authors.forename: Yves
authors.initials: Y
authors.lastname: Bertrand
authors.forename: Jean-Hugues
authors.initials: JH
authors.lastname: Dalle
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.forename: Thierry
authors.initials: T
authors.lastname: Leblanc
authors.forename: André
authors.initials: A
authors.lastname: Baruchel