title: Clofarabine, cyclophosphamide and etoposide as single-course re-induction therapy for children with refractory/multiple relapsed acute lymphoblastic leukaemia.
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.
authors.affiliation: Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Università di Pavia, Italy. f.locatelli@smatteo.pv.it
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Anna M
authors.initials: AM
authors.lastname: Testi
authors.forename: Maria Ester
authors.initials: ME
authors.lastname: Bernardo
authors.forename: Carmelo
authors.initials: C
authors.lastname: Rizzari
authors.forename: Alice
authors.initials: A
authors.lastname: Bertaina
authors.forename: Pietro
authors.initials: P
authors.lastname: Merli
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.forename: Eugenia
authors.initials: E
authors.lastname: Giraldi
authors.forename: Rosanna
authors.initials: R
authors.lastname: Parasole
authors.forename: Walter
authors.initials: W
authors.lastname: Barberi
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage / Q000009:adverse effects; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D000077866:Clofarabine; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D005047:Etoposide; D000077866:Clofarabine; D003520:Cyclophosphamide