title: Substitution of cyclophosphamide and busulfan by fludarabine, treosulfan and melphalan in a preparative regimen for children and adolescents with Shwachman-Diamond syndrome.
abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only definitive treatment for severe bone marrow dysfunction and clonal disorders in patients diagnosed with Shwachman-Diamond syndrome (SDS). In an attempt to minimize regimen-related toxicity (RRT), we have initiated a fludarabine/treosulfan/melphalan-based pilot protocol avoiding the combination of busulfan and cyclophosphamide. Median age at transplantation was 9.6 years (range 1.5-17 years). All three patients received conditioning with fludarabine (30 mg/m2/day x 6), treosulfan (12 g/m2/day x 3) and melphalan (140 mg/m2/day x 1). CAMPATH-1H (0.1 mg/kg x 2) was added in two cases, while rabbit ATG (Genzyme; 3 x 2.5 mg/kg) was given to the cord blood recipient. One patient was transplanted with a non-manipulated marrow graft from an HLA-identical sibling, one with a marrow graft from a 10/10 matched unrelated donor, and one with a 9/10 matched unrelated umbilical cord blood (UCB) unit. Mean cell doses given were 3.6 x 10(8) nucleated cells/kg BW for the bone marrow recipients and 4.2 x 10(7) nucleated cells/kg BW for UCB recipient. Overall, two of three patients are alive and display 100% donor chimerism. Acute graft-versus-host disease grade II was seen in one patient, while no GVHD exceeding grade I occurred in the remaining two.
authors.affiliation: Department of Pediatric Hematology - Oncology, Hannover Medical University, Hannover, Germany. sauer.martin@mh-hannover.de
authors.forename: M
authors.initials: M
authors.lastname: Sauer
authors.forename: C
authors.initials: C
authors.lastname: Zeidler
authors.forename: B
authors.initials: B
authors.lastname: Meissner
authors.forename: K
authors.initials: K
authors.lastname: Rehe
authors.forename: A
authors.initials: A
authors.lastname: Hanke
authors.forename: K
authors.initials: K
authors.lastname: Welte
authors.forename: P
authors.initials: P
authors.lastname: Lohse
authors.forename: K-W
authors.initials: KW
authors.lastname: Sykora
mesh_terms: D000015:Abnormalities, Multiple / Q000188:drug therapy; D000293:Adolescent; D001855:Bone Marrow Diseases / Q000188:drug therapy*; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide; D004359:Drug Therapy, Combination; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D007223:Infant; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D010865:Pilot Projects; D013577:Syndrome; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D003520:Cyclophosphamide; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008558:Melphalan