title: Hematopoietic Cell Transplantation Using Reduced-Intensity Conditioning Is Successful in Children with Hematologic Cytopenias of Genetic Origin.
abstract: Genetically derived hematologic cytopenias are a rare heterogeneous group of disorders. Allogeneic hematopoietic cell transplantation (HCT) is curative but offset by organ toxicities from the preparative regimen, graft rejection, graft-versus-host disease (GVHD), or mortality. Because of these possibilities, consideration of HCT can be delayed, especially in the unrelated donor setting. We report a prospective multicenter trial of reduced-intensity conditioning (RIC) with alemtuzumab, fludarabine, and melphalan and HCT in 11 children with marrow failure of genetic origin (excluding Fanconi anemia) using the best available donor source (82% from unrelated donors). The median age at transplantation was 23 months (range, 2 months to 14 years). The median times to neutrophil (>500 × 10(6)/L) and platelet (>50 × 10(9)/L) engraftment were 13 (range, 12 to 24) and 30 (range, 7 to 55) days, respectively. The day +100 probability of grade II to IV acute GVHD and the 1-year probability of limited and extensive GVHD were 9% and 27%, respectively. The probability of 5-year overall and event-free survival was 82%; 9 patients were alive with normal blood counts at last follow-up and all were successfully off systemic immunosuppression. In patients with genetically derived severe hematologic cytopenias, allogeneic HCT with this RIC regimen was successful in achieving a cure. This experience supports consideration of HCT early in such patients even in the absence of suitable related donors.
authors.affiliation: Department of Pediatrics, Washington University, St. Louis, Missouri.
authors.forename: Alok
authors.initials: A
authors.lastname: Kothari
authors.affiliation: Department of Pediatrics, Washington University, St. Louis, Missouri.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ngwube
authors.affiliation: Department of Pediatrics, Washington University, St. Louis, Missouri.
authors.forename: Robert
authors.initials: R
authors.lastname: Hayashi
authors.affiliation: Department of Pediatrics, Washington University, St. Louis, Missouri.
authors.forename: Lisa
authors.initials: L
authors.lastname: Murray
authors.affiliation: Department of Pediatrics, Children's and Women's Health Centre of BC, Vancouver, BC, Canada.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Davis
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Paul
authors.initials: P
authors.lastname: Haut
authors.affiliation: Department of Pediatrics, Children's National Medical Center, Washington, D.C.
authors.forename: Brett J
authors.initials: BJ
authors.lastname: Loechelt
authors.affiliation: Department of Pediatrics, Washington University, St. Louis, Missouri. Electronic address: shenoy@wustl.edu.
authors.forename: Shalini
authors.initials: S
authors.lastname: Shenoy
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D009503:Neutropenia / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D011446:Prospective Studies; D012306:Risk; D035781:Siblings; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan
keywords: Congenital hematologic cytopenias; Hematopoietic cell transplantation; Reduced-intensity conditioning