title: Hematopoietic stem cell transplantation (HSCT) with a conditioning regimen of busulfan, cyclophosphamide, and etoposide for children with acute myelogenous leukemia (AML): a phase I study of the Pediatric Blood and Marrow Transplant Consortium.
abstract: BACKGROUND
  Hematopoietic stem cell transplantation (HSCT) is an important treatment modality for children with AML. The optimal conditioning regimen is unknown. The aim of this study was to determine the appropriate dosing of etoposide in combination with busulfan and cyclophosphamide in this setting.
  
  
  METHODS
  Twenty patients with a diagnosis of AML in first or second remission, or myelodysplasia scheduled for bone marrow transplantation, were included in this study. Patients received busulfan 640 mg/m(2) in 16 doses, cyclophosphamide 120 to 150 mg/kg in two doses, and etoposide from 40-60 mg/kg as a single dose. Extensive toxicity data was collected.
  
  
  RESULTS
  Nineteen patients were evaluable for toxicity. Mucositis was seen in all patients. Four patients developed bacteremia and one patient died from overwhelming sepsis on day +3. Four patients developed moderate to severe skin toxicity. The major dose-limiting +3 toxicity was hepatic toxicity, which occurred in 14 of 19 patients. Eight patients developed clinical veno-occlusive disease, including three patients at dose level 4, two of whom had life-threatening disease. This hepatic toxicity defined the MTD of 640 mg/m(2) busulfan, 120 mg/kg of cyclophosphamide, and 60 mg/kg of etoposide. Overall, 9 of 20 patients enrolled in the study survive in remission, 8/14 allogeneic (median follow-up 44 months), and one of six autologous patients (follow-up, 54 months).
  
  
  CONCLUSIONS
  We conclude that the combination of busulfan, cyclophosphamide, and etoposide at the doses defined above has activity in the treatment of children with high-risk AML/MDS undergoing allogeneic HSCT. Whether it offers an advantage over other conditioning regimens will require a randomized trial with a larger cohort of patients.
authors.affiliation: UT Southwestern Medical School and Children's Hospital of Dallas, Dallas, Texas, USA. esandler@nemours.org
authors.forename: E S
authors.initials: ES
authors.lastname: Sandler
authors.forename: R
authors.initials: R
authors.lastname: Hagg
authors.forename: M J
authors.initials: MJ
authors.lastname: Coppes
authors.forename: M M
authors.initials: MM
authors.lastname: Mustafa
authors.forename: A
authors.initials: A
authors.lastname: Gamis
authors.forename: N
authors.initials: N
authors.lastname: Kamani
authors.forename: D
authors.initials: D
authors.lastname: Wall
mesh_terms: D000293:Adolescent; D000416:Alberta; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D008297:Male; D008923:Missouri; D013781:Texas; D019172:Transplantation Conditioning; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide; D002066:Busulfan