Treatment of chronic granulomatous disease with myeloablative conditioning and an unmodified hemopoietic allograft: a survey of the European experience, 1985-2000.
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.
Seger
Reinhard A
RA
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
Gungor
Tayfun
T
Belohradsky
Bernd H
BH
Blanche
Stephane
S
Bordigoni
Pierre
P
Di Bartolomeo
Paolo
P
Flood
Terence
T
Landais
Paul
P
Müller
Susanna
S
Ozsahin
Hulya
H
Passwell
Justen H
JH
Porta
Fulvio
F
Slavin
Shimon
S
Wulffraat
Nico
N
Zintl
Felix
F
Nagler
Arnon
A
Cant
Andrew
A
Fischer
Alain
A
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*
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