title: Total body irradiation, fludarabine, melphalan, and allogeneic hematopoietic stem cell transplantation for advanced pediatric hematologic malignancies.
abstract: We evaluated the efficacy and toxicity of adding 9 Gy of total body irradiation (TBI), in three single daily fractions of 3 Gy, to the reduced intensity regimen of fludarabine 30 mg/m2 i.v. x 4 days and melphalan 140 mg/m2 i.v. x 1 day in advanced pediatric hematologic malignancies. Twenty-two acute lymphoblastic leukemia (ALL), six acute myeloid leukemia (AML), and one non-Hodgkin lymphoma patients were transplanted. Of these, 13 were beyond second remission, and five had prior hematopoietic stem cell transplant (HSCT). Twenty-one donors were unrelated, of which 19 were from cord blood (CB) units. Three of the eight related donors were genotypically disparate. Oral mucositis and diarrhea were the most common toxicities. Twenty-seven patients achieved neutrophil engraftment (median 16 days), and 23 had platelet engraftment (median 42 days). One patient had primary graft failure. Seven patients died of non-relapse causes in the first 100 days. With a median follow-up of 52 months, seven of 22 ALL, five of six AML, and one of one lymphoma patients are alive and in remission. The regimen of TBI, fludarabine, and melphalan allows the engraftment of allogeneic hematopoietic stem cells (including mismatched CB). It was fairly well tolerated in pediatric patients, even for second transplants. Its efficacy requires further evaluation.
authors.affiliation: Department of Pediatrics, M.D. Anderson Cancer Center Houston, TX, USA.
authors.forename: D
authors.initials: D
authors.lastname: Petropoulos
authors.forename: L L
authors.initials: LL
authors.lastname: Worth
authors.forename: C A
authors.initials: CA
authors.lastname: Mullen
authors.forename: R
authors.initials: R
authors.lastname: Madden
authors.forename: A
authors.initials: A
authors.lastname: Mahajan
authors.forename: M
authors.initials: M
authors.lastname: Choroszy
authors.forename: C S
authors.initials: CS
authors.lastname: Ha
authors.forename: R C
authors.initials: RC
authors.lastname: Champlin
authors.forename: K W
authors.initials: KW
authors.lastname: Chan
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000401:mortality; D003967:Diarrhea / Q000209:etiology; D005260:Female; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D009061:Mouth Mucosa; D013280:Stomatitis / Q000209:etiology; D015996:Survival Rate; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014916:Whole-Body Irradiation
chemical_list: D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan