title: Favorable outcome of hematopoietic stem cell transplantation using a targeted once-daily intravenous busulfan-fludarabine-etoposide regimen in pediatric and infant acute lymphoblastic leukemia patients.
abstract: Conditioning regimens for pediatric acute lymphoblastic leukemia (ALL) usually include total body irradiation (TBI), but TBI may result in serious sequelae. Busulfan and cyclophosphamide have been used as an alternative to TBI. Etoposide also has been widely used to enhance antileukemic effect. However, toxicities have been reported in some studies using busulfan, cyclophosphamide, and etoposide regimen. A reduced toxicity myeloablative regimen using busulfan and fludarabine showed promising results. Also, therapeutic drug monitoring (TDM) and administration of targeted doses of busulfan have been recommended to improve the outcome of hematopoietic stem cell transplantation (HSCT). In this study, we evaluated the outcome of HSCT using a targeted once-daily i.v. busulfan-fludarabine-etoposide (BuFluVP) regimen in pediatric and infant ALL. Busulfan (age ≥ 1 year, 120 mg/m(2); age < 1 year, 80 mg/m(2)) was administered once daily as the first dose on day -8, and a targeted dose of busulfan was used according to the TDM results on days -7 to -5. Forty-four patients were evaluated. Donor-type neutrophil engraftment was achieved in all patients. Veno-occlusive disease occurred in 7 patients (15.9%), but all patients were successfully treated. Cumulative incidence of treatment-related mortality and relapse were 9.1% and 9.9%, respectively. One-year overall survival and event-free survival rates of all patients were 86.2% and 83.8%, respectively. Twelve patients (27.3%) were infants at diagnosis, and their 1-year overall survival rate was 83.3%. Our study demonstrated that HSCT using a targeted once-daily i.v. BuFluVP regimen showed favorable outcomes and could be an option for HSCT in pediatric and infant ALL.
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: kanghj@snu.ac.kr.
authors.forename: Hyoung Jin
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sungjin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung-Sang
authors.initials: KS
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Nam Hee
authors.initials: NH
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Jang
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyery
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Song
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: June Dong
authors.initials: JD
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung Duk
authors.initials: KD
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Shin
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyo Seop
authors.initials: HS
authors.lastname: Ahn
mesh_terms: D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007275:Injections, Intravenous; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012008:Recurrence; D012189:Retrospective Studies; D035781:Siblings; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D005047:Etoposide; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine
keywords: Acute lymphoblastic leukemia; Busulfan; Fludarabine; Stem cell transplantation; Therapeutic drug monitoring