title: Treosulfan-based preparative regimens for allo-HSCT in childhood hematological malignancies: a retrospective study on behalf of the EBMT pediatric diseases working party.
abstract: This retrospective analysis evaluated 51 children (0.7-17 years; median eight) with high-risk or advanced hematological malignancies, including 18 (35%) patients undergoing second/third hematopoietic SCT (allo-HSCT), not eligible for standard myeloablative regimens and transplanted from matched sibling (MSD) (n=24) or matched unrelated (MUD) (n=27) donors. Preparative regimens were based on treosulfan (TREO) i.v., a structural analog of BU, given at total dose of 30 g/m(2) (n=21) or 36-42 g/m(2) (n=30) in combination with, fludarabine, cyclophosphamide, melphalan and/or VP-16 according to diagnosis, and risk factors. Deaths due to early regimen-related toxicity (RRT) did not occur. Nonrelapse mortality was 8% at 1 year and 16% after 4 years. Myeloid engraftment was achieved in 94%, complete donor chimerism in 90% of patients. A 4-year incidence of relapse was 24%, and was significantly lower after MUD-HSCT (8%) than after MSD-HSCT (39%), but similar in children undergoing first (28%) or second/third HSCT (17%). A 4-year disease-free survival was 61%, but it was significantly better in myeloid (73%), than in lymphoid malignancies (41%). Thus, children with high-risk and advanced hematological malignancies and high-risk of life-threatening RRT can be transplanted effectively and safely using TREO-based regimens. Particularly favorable results were achieved in myeloid malignancies and in children undergoing second HSCT.
authors.affiliation: Department of Pediatric Oncology, Hematology and HSCT, University of Medical Sciences, Poznan, Poland. jacek.wachowiak@plusnet.pl
authors.forename: J
authors.initials: J
authors.lastname: Wachowiak
authors.forename: K-W
authors.initials: KW
authors.lastname: Sykora
authors.forename: J
authors.initials: J
authors.lastname: Cornish
authors.forename: A
authors.initials: A
authors.lastname: Chybicka
authors.forename: J R
authors.initials: JR
authors.lastname: Kowalczyk
authors.forename: E
authors.initials: E
authors.lastname: Gorczyńska
authors.forename: M
authors.initials: M
authors.lastname: Choma
authors.forename: G
authors.initials: G
authors.lastname: Grund
authors.forename: C
authors.initials: C
authors.lastname: Peters
mesh_terms: D000293:Adolescent; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002330:Carmustine / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D019337:Hematologic Neoplasms / Q000401:mortality* / Q000628:therapy*; D006801:Humans; D007223:Infant; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D012189:Retrospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D018906:Antineoplastic Agents, Alkylating; D005047:Etoposide; D003520:Cyclophosphamide; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008558:Melphalan; D002330:Carmustine