title: Treatment of chronic granulomatous disease with myeloablative conditioning and an unmodified hemopoietic allograft: a survey of the European experience, 1985-2000.
abstract: Treatment of chronic granulomatous disease (CGD) with myeloablative bone marrow transplantation is considered risky. This study investigated complications and survival according to different risk factors present at transplantation. The outcomes of 27 transplantations for CGD, from 1985 to 2000, reported to the European Bone Marrow Transplant Registry for primary immunodeficiencies were assessed. Most transplant recipients were children (n = 25), received a myeloablative busulphan-based regimen (n = 23), and had unmodified marrow allografts (n = 23) from human leukocyte antigen (HLA)-identical sibling donors (n = 25). After myeloablative conditioning, all patients fully engrafted with donor cells; after myelosuppressive regimens, 2 of 4 patients fully engrafted. Severe (grade 3 or 4) graft-versus-host disease (GVHD) disease developed in 4 patients: 3 of 9 with pre-existing overt infection, 1 of 2 with acute inflammatory disease. Exacerbation of infection during aplasia was observed in 3 patients; inflammatory flare at the infection site during neutrophil engraftment in 2: all 5 patients belonged to the subgroup of 9 with pre-existing infection. Overall survival was 23 of 27, with 22 of 23 cured of CGD (median follow-up, 2 years). Survival was especially good in patients without infection at the moment of transplantation (18 of 18). Pre-existing infections and inflammatory lesions have cleared in all survivors (except in one with autologous reconstitution). Myeloablative conditioning followed by transplantation of unmodified hemopoietic stem cells, if performed at the first signs of a severe course of the disease, is a valid therapeutic option for children with CGD having an HLA-identical donor.
authors.affiliation: European Group for Blood and Marrow Transplantation (EBMT) and the European Society for Immunodeficiencies (ESID), Division of Immunology/Hematology, University Children's Hospital, Zurich, Switzerland. reinhard.seger@kispi.unizh.ch
authors.forename: Reinhard A
authors.initials: RA
authors.lastname: Seger
authors.forename: Tayfun
authors.initials: T
authors.lastname: Gungor
authors.forename: Bernd H
authors.initials: BH
authors.lastname: Belohradsky
authors.forename: Stephane
authors.initials: S
authors.lastname: Blanche
authors.forename: Pierre
authors.initials: P
authors.lastname: Bordigoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Bartolomeo
authors.forename: Terence
authors.initials: T
authors.lastname: Flood
authors.forename: Paul
authors.initials: P
authors.lastname: Landais
authors.forename: Susanna
authors.initials: S
authors.lastname: Müller
authors.forename: Hulya
authors.initials: H
authors.lastname: Ozsahin
authors.forename: Justen H
authors.initials: JH
authors.lastname: Passwell
authors.forename: Fulvio
authors.initials: F
authors.lastname: Porta
authors.forename: Shimon
authors.initials: S
authors.lastname: Slavin
authors.forename: Nico
authors.initials: N
authors.lastname: Wulffraat
authors.forename: Felix
authors.initials: F
authors.lastname: Zintl
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Andrew
authors.initials: A
authors.lastname: Cant
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
mesh_terms: D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000961:Antilymphocyte Serum; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D002066:Busulfan; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide; D005060:Europe; D005260:Female; D018740:Genetic Heterogeneity; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology; D006105:Granulomatous Disease, Chronic / Q000235:genetics / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000706:statistics & numerical data*; D006801:Humans; D017053:Infection Control; D007239:Infections / Q000150:complications; D007249:Inflammation; D008297:Male; D008558:Melphalan; D009504:Neutrophils / Q000502:physiology; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000706:statistics & numerical data*; D014184:Transplantation, Homologous / Q000009:adverse effects; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000961:Antilymphocyte Serum; D000074323:Alemtuzumab; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008558:Melphalan