title: A comparison of immune reconstitution and graft-versus-host disease following myeloablative conditioning versus reduced toxicity conditioning and umbilical cord blood transplantation in paediatric recipients.
abstract: Immune reconstitution appears to be delayed following myeloablative conditioning (MAC) and umbilical cord blood transplantation (UCBT) in paediatric recipients. Although reduced toxicity conditioning (RTC) versus MAC prior to allogeneic stem cell transplantation is associated with decreased transplant-related mortality, the effects of RTC versus MAC prior to UCBT on immune reconstitution and risk of graft-versus-host disease (GVHD) are unknown. In 88 consecutive paediatric recipients of UCBT, we assessed immune cell recovery and immunoglobulin reconstitution at days +100, 180 and 365 and analysed risk factors associated with acute and chronic GVHD. Immune cell subset recovery, immunoglobulin reconstitution, and the incidence of opportunistic infections did not differ significantly between MAC versus RTC groups. In a Cox model, MAC versus RTC recipients had significantly higher risk of grade II-IV acute GVHD [Hazard Ratio (HR) 6·1, P = 0·002] as did recipients of 4/6 vs. 5-6/6 HLA-matched UCBT (HR 3·1, P = 0·03), who also had significantly increased risk of chronic GVHD (HR 18·5, P = 0·04). In multivariate analyses, MAC versus RTC was furthermore associated with significantly increased transplant-related (Odds Ratio 26·8, P = 0·008) and overall mortality (HR = 4·1, P = 0·0001). The use of adoptive cellular immunotherapy to accelerate immune reconstitution and prevent and treat opportunistic infections and malignant relapse following UCBT warrants further investigation.
authors.affiliation: Department of Pediatrics, NewYork-Presbyterian Morgan Stanley Children's Hospital, Columbia University, New York, NY, USA.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Geyer
authors.forename: Judith S
authors.initials: JS
authors.lastname: Jacobson
authors.forename: Jason
authors.initials: J
authors.lastname: Freedman
authors.forename: Diane
authors.initials: D
authors.lastname: George
authors.forename: Virginia
authors.initials: V
authors.lastname: Moore
authors.forename: Carmella
authors.initials: C
authors.lastname: van de Ven
authors.forename: Prakash
authors.initials: P
authors.lastname: Satwani
authors.forename: Monica
authors.initials: M
authors.lastname: Bhatia
authors.forename: James H
authors.initials: JH
authors.lastname: Garvin
authors.forename: Mary Brigid
authors.initials: MB
authors.lastname: Bradley
authors.forename: Lauren
authors.initials: L
authors.lastname: Harrison
authors.forename: Erin
authors.initials: E
authors.lastname: Morris
authors.forename: Phyllis
authors.initials: P
authors.lastname: Della-Latta
authors.forename: Joseph
authors.initials: J
authors.lastname: Schwartz
authors.forename: Lee A
authors.initials: LA
authors.lastname: Baxter-Lowe
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Cairo
mesh_terms: D000074323:Alemtuzumab; D019072:Antibiotic Prophylaxis; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000627:therapeutic use; D000961:Antilymphocyte Serum; D002066:Busulfan / Q000008:administration & dosage / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D030342:Genetic Diseases, Inborn / Q000601:surgery; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000627:therapeutic use; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D009369:Neoplasms / Q000601:surgery; D009504:Neutrophils; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D013601:T-Lymphocytes; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D014916:Whole-Body Irradiation
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000961:Antilymphocyte Serum; D019653:Myeloablative Agonists; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000074323:Alemtuzumab; C081222:sargramostim; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008558:Melphalan