Published online March 2, 2009
PEDIATRICS Vol. 123 No. 3 March 2009, pp. 836-840 (doi:10.1542/peds.2008-1191)

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ARTICLE

Allogeneic Hematopoietic Stem-Cell Transplantation for Leukocyte Adhesion Deficiency

Waseem Qasim, PhD, MBBS^a, Marina Cavazzana-Calvo, MD, PhD^b, E. Graham Davies, MBBChir^a, Jeffery Davis, MD^c, Michel Duval, MD^d, Gretchen Eames, MD^e, Nuno Farinha, MD^f, Alexandra Filopovich, MD^g, Alain Fischer, MD, PhD^b, Wilhelm Friedrich, MD^h, Andrew Gennery, MD, MBChBⁱ, Carsten Heilmann, MD^j, Paul Landais, MD^b, Mitchell Horwitz, MD^k, Fulvio Porta, MD^l, Petr Sedlacek, MD, PhD^m, Reinhard Seger, MDⁿ, Mary Slatten, MBBSrⁱ, Lochie Teague, MD^o, Mary Eapen, MBBS^p and Paul Veys, MBBS^a

^a Department of Immunology, Great Ormond Street Hospital, London, United Kingdom
^b Department of Immunology, Hôpital Necker Enfants Malades, Paris, France
^c Department of Pediatrics, British Columbia Children's Hospital, Vancouver, British Columbia, Canada
^d Service d'Hemato-Oncologie, Hopital Sainte Justine, Montreal, Quebec, Canada
^e Department of Blood and Marrow Transplantation, Cook Children's Medical Center, Fort Worth, Texas
^f Hematology and Oncology Unit, Hospital de S. Joao, Porto, Portugal
^g Department of Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
^h Department of Blood and Marrow Transplantation, Universitaet Ulm, Ulm, Germany
ⁱ Department of Immunology, Newcastle General Hospital, Newcastle-Upon-Tyne, United Kingdom
^j Department of Blood and Marrow Transplantation, Rigshospitalet, Copenhagen, Denmark
^k Division of Cellular Therapy, Duke University Medical Center, Durham, North Carolina
^l Clinica Pediatrica, Universitá Degli Studi di Brescia, Brescia, Italy
^m Department of Paediatric Haematology and Oncology, University Hospital Motol, Prague, Czech Republic
ⁿ Division of Immunology, Hematology, and Oncology, University Children's Hospital, Zürich, Switzerland
^o Paediatric Haematology and Oncology, Starship Children's Hospital, Auckland, New Zealand
^p Center for International Blood and Marrow Transplant Research Statistical Center, Medical College of Wisconsin, Milwaukee, Wisconsin

OBJECTIVES. Leukocyte adhesion deficiency is a rare primary immune disorder caused by defects of the CD18 β-integrin molecule on immune cells. The condition usually presents in early infancy and is characterized by deep tissue infections, leukocytosis with impaired formation of pus, and delayed wound healing. Allogeneic hematopoietic stem-cell transplantation offers the possibility of curative therapy, and with patient numbers at any individual center being limited, we surveyed the transplant experience at 14 centers worldwide.

METHODS. The course of 36 children with a confirmed diagnosis of leukocyte adhesion deficiency who underwent hematopoietic stem-cell transplantation between 1993 and 2007 was retrospectively analyzed. Data were collected by the registries of the European Society for Immunodeficiencies/European Group for Blood and Marrow Transplantation, and the Center for International Blood and Marrow Transplant Research.

RESULTS. At a median follow-up of 62 months (extending to 14 years), the overall survival rate was 75%. Myeloablative conditioning regimens were used in 28 patients, and reduced-intensity conditioning in 8 patients, with no deaths in this subgroup. Survival rates after matched family donor and unrelated donor transplants were similar, with 11 of 14 matched family donor and 12 of 14 unrelated donor recipients alive; mortality was greatest after haploidentical transplants, after which 4 of 8 children did not survive. Twenty-seven transplant recipients were alive, with full donor engraftment in 17 cases, mixed multilineage chimerism in 7 patients, and mononuclear cell-restricted chimerism in an additional 3 cases.

CONCLUSIONS. Hematopoietic stem-cell transplantation offers long-term benefit in leukocyte adhesion deficiency and should be considered as an early therapeutic option if a suitable HLA-matched stem-cell donation is available. Reduced-intensity conditioning was particularly safe, and mixed-donor chimerism seems sufficient to prevent significant symptoms, although careful long-term monitoring will be required for these patients.

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Key Words: leukocyte adhesion deficiency • stem-cell transplantation • reduced-intensity conditioning

Abbreviations: ATG—antithymocyte globulin • CLAD—canine leukocyte adhesion deficiency • CMV—cytomegalovirus • EBV—Epstein-Barr virus • GVHD—graft-versus-host disease • HSCT—hematopoietic stem-cell transplantation • LAD—leukocyte adhesion deficiency • LFA-1—lymphocyte function associated antigen-1 • MFD—matched family donor • PBSC—peripheral blood stem-cell collection • RIC—reduced-intensity conditioning

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Accepted Jun 30, 2008.

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HSCT for leukocyte adhesion deficiency

Geoffrey A. Weinberg, MD, et al.

Pediatrics Online, 11 Sep 2009 [Full text]