Clofarabine, cyclophosphamide and etoposide for the treatment of relapsed or resistant acute leukemia in pediatric patients

• Published in: Leukemia & lymphoma 2012-09, Vol.53 (9), p.1693-1698
• Main Authors: Miano, Maurizio, Pistorio, Angela, Putti, Maria C., Dufour, Carlo, Messina, Chiara, Barisone, Elena, Ziino, Ottavio, Parasole, Rosanna, Luciani, Matteo, Lo Nigro, Luca, Rossi, Giulio De, Varotto, Stefania, Bertorello, Nicoletta, Petruzziello, Fara, Calvillo, Michaela, Micalizzi, Concetta
• Format: Article
• Language: English
• Subjects: Acute Disease; 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; Chemical and Drug Induced Liver Injury - etiology; Child; Child, Preschool; Clofarabine; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Drug Administration Schedule; Etoposide - administration & dosage; Etoposide - adverse effects; Female; Gastrointestinal Diseases - chemically induced; hematopoietic stem cell transplant; Humans; Infant; Kaplan-Meier Estimate; Leukemia, Myeloid - drug therapy; Leukemia, Myeloid - pathology; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Prospective Studies; Recurrence; relapsed/resistant pediatric leukemia; Remission Induction; Treatment Outcome
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428194.2012.663915

Abstract Clofarabine is a promising new chemotherapeutic agent that is active in the treatment of pediatric acute leukemia. Forty children (16 with acute myeloid leukemia [AML], 24 with acute lymphoblastic leukemia [ALL]), aged 1-20 years (median 7.6 years) with relapsed or refractory ALL or AML were treated because of resistance to first-line treatment (n =5), or for first (n =22), second (n =11) or third relapse (n =2). They received clofarabine (40 mg/m2/day) associated with etoposide (100 mg/m2/day) and cyclophosphamide (440 mg/m2/day) administered as one or two induction cycles (5 days of chemotherapy) in an attempt to reach complete remission (CR) or CR without platelet recovery (CRp). This was followed by 1-3 consolidation cycles (4 days of chemotherapy) for a maximum of four cycles. Seven (44%) out of 16 and 10 (42%) out of 24 evaluable children with AML and ALL, respectively, responded to treatment. The most common adverse events were infections and gastrointestinal and hepatic toxicity. Thirteen (76%) out of 17 responders underwent hematopoietic stem cell transplant. The 24-month overall survival was 25%, while it was 59% among patients who responded to the first induction cycle. Our study suggests that this drug regimen is well tolerated and can be effective in heavily pretreated pediatric patients with relapsed or refractory acute leukemia.