title: Outcomes of donor lymphocyte infusion for treatment of mixed donor chimerism after a reduced-intensity preparative regimen for pediatric patients with nonmalignant diseases.
abstract: Mixed donor chimerism is increasingly common in the pediatric hematopoietic stem cell transplantation (HSCT) setting because of the increased use of reduced-intensity preparative regimens for nonmalignant diseases. Donor lymphocyte infusion (DLI) is potentially useful in the treatment of mixed donor chimerism, but little are data available on the use of DLI in this setting. We conducted a retrospective review of 27 pediatric patients who received DLI for mixed donor chimerism between January 2006 and December 2010 after receiving a preparative regimen of alemtuzumab, fludarabine, and melphalan. Twenty-one patients (78%) were alive at a median of 35 months post-transplant. Seven patients (26%) sustained full donor chimerism after DLI only at a median of 35 months post-HSCT. Nine patients (33%) continued with mixed donor chimerism (median, 38% [range, 18% to 70%]) at a median of 37 months after DLI only. Five patients underwent unconditioned stem cell boosts or second conditioned transplants after no improvement in donor chimerism was seen following DLI. Donor source appeared to contribute to outcomes after DLI; patients with mismatched unrelated donors had earlier first decline in chimerism and timing of first DLI, a higher response rate to DLI, and an increased rate of graft-versus-host disease (GVHD). There was no response to DLI in patients with matched sibling donors. Ten patients, all with improvement in chimerism after DLI, developed acute GVHD after DLI, with 3 having grade III GVHD. Three patients developed chronic GVHD after DLI. These data illustrate the potential efficacy of DLI in the treatment of mixed donor chimerism after a reduced-intensity preparative regimen.
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Alabama Birmingham, Birmingham, Alabama.
authors.forename: Hilary L
authors.initials: HL
authors.lastname: Haines
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Bleesing
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
authors.affiliation: Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Hornung
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Jordan
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Marsh
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: lisa.filipovich@cchmc.org.
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
mesh_terms: D000293:Adolescent; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D046528:Chimerism; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D017710:Lymphocyte Transfusion; D051359:Lymphohistiocytosis, Hemophagocytic / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D009083:Mucopolysaccharidoses / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D019653:Myeloablative Agonists / Q000627:therapeutic use; D012189:Retrospective Studies; D016511:Severe Combined Immunodeficiency / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D035781:Siblings; 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; D019653:Myeloablative Agonists; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan
keywords: Donor lymphocyte infusion (DLI); Mixed donor chimerism; Nonmalignant disease; Pediatrics; Reduced-intensity conditioning