title: Hematopoietic stem cell transplantation for childhood myeloid malignancies after high-dose thiotepa, busulfan and cyclophosphamide.
abstract: Seventeen children with advanced myeloid malignancies (induction failure, relapse, myelodysplasia, secondary AML, or CR >1) received thiotepa 750 mg/m2 i.v., busulfan 12 mg/kg or 640 mg/m2 p.o., and cyclophosphamide 120 mg/kg i.v. as a preparative regimen for allogeneic or autologous hematopoietic stem cell (HSC) transplantation. Of the 15 allogeneic transplants, eight were from matched siblings, one was from a mismatched sibling, and six were from unrelated donors. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine or tacrolimus and methotrexate. Regimen-related toxicity was common but tolerable, affecting mainly the skin and gastrointestinal tract. Three patients died early and were not evaluable for engraftment; engraftment occurred in the remaining patients. Nine patients with active disease at the time of transplant were evaluable for response; all achieved remission. With a median follow-up of 40 months (range, 10-71 months), nine patients are alive and disease-free. The 3-year actuarial event-free survival was 51% (95% confidence interval (CI) 27-76%). Seven patients died of transplant-related complications: infection (n = 4), chronic GVHD (n = 1), veno-occlusive disease, VOD, (n= 1) and pulmonary alveolar hemorrhage (n = 1). Only one patient had leukemia relapse and died. We conclude that the use of high-dose thiotepa, busulfan and cyclophosphamide is an effective conditioning regimen for childhood myeloid malignancies and may be tested in patients with less advanced disease (eg CR1).
authors.affiliation: Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: L
authors.initials: L
authors.lastname: Worth
authors.forename: H
authors.initials: H
authors.lastname: Tran
authors.forename: D
authors.initials: D
authors.lastname: Petropoulos
authors.forename: S
authors.initials: S
authors.lastname: Culbert
authors.forename: C
authors.initials: C
authors.lastname: Mullen
authors.forename: W
authors.initials: W
authors.lastname: Roberts
authors.forename: D
authors.initials: D
authors.lastname: Przepiorka
authors.forename: K
authors.initials: K
authors.lastname: Chan
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002066:Busulfan / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000628:therapy*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000628:therapy*; D013852:Thiotepa / Q000008:administration & dosage; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
chemical_list: D003520:Cyclophosphamide; D013852:Thiotepa; D002066:Busulfan