Allogeneic bone marrow transplantation for children with acute leukemia: cytoreduction with fractionated total body irradiation, high-dose etoposide and cyclophosphamide.
Marrow-ablative chemo-radiotherapy followed by hematopoietic stem cell rescue from an allogeneic source improves outcomes for children with high-risk acute leukemia. The first effective pre-transplant preparative regimens consisted of high-dose cyclophosphamide (CY) and total body irradiation (TBI). Subsequent attempts have been made to improve leukemia-free survival, by adding other chemotherapy agents to these agents. In previous clinical studies of total body irradiation, etoposide, cyclophosphamide (TBI-VP-16-Cy) in adult allogeneic bone marrow transplantation, there has been a high incidence of severe regimen-related toxicity. In this study, we investigated the safety and efficacy of this combination in 41 children who received TBI (12-14 Gy), VP-16 (30 mg/kg), and CY (60 mg/kg x 2) and then either matched sibling or alternative donor transplants for acute leukemia. There was only one case of fatal regimen-related toxicity. The estimated 3-year event-free survival for patients with early or intermediate stage disease was 68% (53-88%). The estimated event-free survival of patients with advanced disease was 17% (5-59%). TBI-VP16-CY is safe in pediatric transplantation, and it has good efficacy for transplant recipients with less advanced disease. Bone Marrow Transplantation (2000) 25, 489-494.
Duerst
R E
RE
Department of Pediatrics, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642, USA.
Horan
J T
JT
Liesveld
J L
JL
Abboud
C N
CN
Zwetsch
L M
LM
Senf
E S
ES
Constine
L S
LS
Raubertas
R F
RF
Passarell
J A
JA
DiPersio
J F
JF
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D001788:Blood Grouping and Crossmatching; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D064420:Drug-Related Side Effects and Adverse Reactions; D005047:Etoposide / Q000008:administration & dosage / Q000633:toxicity; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000628:therapy*; D019653:Myeloablative Agonists / Q000627:therapeutic use / Q000633:toxicity; D009679:Nuclear Family; D012008:Recurrence; D013280:Stomatitis / Q000139:chemically induced; D015996:Survival Rate; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D019653:Myeloablative Agonists; D005047:Etoposide; D003520:Cyclophosphamide