Hematopoietic Stem Cell Transplantation for CD40 Ligand Deficiency: Single Institution Experience.
BACKGROUND
X-linked hyper-IgM syndrome (X-HIGM) due to mutations in the gene encoding CD40 ligand results in failure of Ig class switching and an increased propensity for recurrent sinopulmonary and other infections, and thus decreased life expectancy. Allogeneic hematopoietic stem cell transplantation (HSCT) is curative, but long-term follow-up data are limited.


METHODS
We conducted a retrospective analysis of seven patients who have undergone allogeneic HSCT for HIGM syndrome at Duke University Medical Center.


RESULTS
Median age at transplant was 5.2 years (range 0.7-19.3). None of the patients had active hepatic or pulmonary disease immediately prior to transplant, but all had a history of serious infections. Five patients received myeloablative conditioning, and two patients received reduced intensity conditioning. Graft sources included bone marrow, peripheral blood, and unrelated umbilical cord blood. Post-transplantation complications included veno-occlusive disease, hemorrhagic cystitis, adenoviremia, and cryptosporidium recurrence in one patient each. Two patients developed acute GVHD grades II-IV that resolved promptly with treatment and none developed extensive chronic GVHD. All patients are intravenous IgG-independent and 6/7 have normal antibody titers. Immunoglobulin (Ig) A levels normalized in all but one patient and T and B cell numbers and function are otherwise normal in all. All patients are alive at a median follow-up of 9.7 (range 9.7-16.1) years post-transplantation with predominantly donor chimerism and no recurrent infections.


CONCLUSIONS
Allogeneic HSCT results in excellent survival and sustained immune reconstitution in patients with CD40 ligand deficiency using both myeloablative and reduced intensity conditioning approaches and various graft sources, including bone marrow, peripheral blood, and umbilical cord blood.
Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
Heather
H
Allewelt
Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
Paul L
PL
Martin
Division of Blood and Marrow Transplantation and Cellular Therapies, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
Paul
P
Szabolcs
Division of Hematologic Malignancies and Cellular Therapy/BMT, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Nelson
N
Chao
Division of Immunology, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
Rebecca
R
Buckley
Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
Suhag
S
Parikh
D000257:Adenoviridae Infections / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000401:mortality; D000293:Adolescent; D000328:Adult; D064591:Allografts; D023201:CD40 Ligand / Q000172:deficiency*; D002648:Child; D002675:Child, Preschool; D003457:Cryptosporidiosis / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000401:mortality; D003556:Cystitis / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053307:Hyper-IgM Immunodeficiency Syndrome, Type 1 / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage; D007223:Infant; D008297:Male; D011668:Pulmonary Veno-Occlusive Disease / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000401:mortality; D020127:Recovery of Function / Q000276:immunology*; D012189:Retrospective Studies; D019172:Transplantation Conditioning
D016756:Immunoglobulins, Intravenous; D023201:CD40 Ligand
CD40 ligand deficiency; bone marrow transplantation; hyper-IgM syndrome; reduced intensity conditioning; umbilical cord blood transplantation