title: CD40 ligand deficiency with grade III liver fibrosis, transplanted by a treosulphan-based conditioning regimen.
abstract: X-linked Hyper IgM is characterized by an absence of the CD40 ligand on activated T lymphocytes resulting in defects of both cellular and humoral immunity. Patients usually present with recurrent bacterial and opportunistic infections. Chronic liver disease is seen in about 75% of patients as a complication. Here, we report a 3.5-year-old boy with X-linked Hyper IgM referred to our clinic for bone marrow transplant. He was transplanted from an HLA-identical sibling donor using a new conditioning agent, treosulphan, together with cyclophosphamide. Since 6 months of age, he has had recurrent respiratory infections, and his XHIGM was diagnosed when he was 1.5 years old. The diagnosis was confirmed by sequence analysis of the CD40L gene. On physical examination, growth failure, bilateral fine crackles in both lungs, and hepatosplenomegaly were detected. The results of his liver function tests were abnormal, and a liver biopsy showed grade III fibrosis and compensated cirrhosis. After conditioning with treosulphan (12 g/m(2)/d x 3 d) and cyclophosphamide (50 mg/kg/d x 4 d), bone marrow from his HLA-identical sister was infused. CD40L expression on activated lymphocytes of the patient was 84% on day +21. His posttransplant period was uneventful. He is now at posttransplant 2 years, with full donor chimerism, and mild, chronic, graft-versus-host disease on his tongue. In conclusion, treosulphan is a new agent for conditioning regimen with less toxicity in patients with severe liver disease.
authors.affiliation: Ankara University, School of Medicine, Department of Pediatric Immunology-Allergy, Ankara, Turkey.
authors.forename: Figen
authors.initials: F
authors.lastname: Dogu
authors.forename: Funda Erol
authors.initials: FE
authors.lastname: Cipe
authors.forename: Ismail
authors.initials: I
authors.lastname: Reisli
authors.forename: Esra
authors.initials: E
authors.lastname: Erden
authors.forename: Aydan
authors.initials: A
authors.lastname: Ikinciogullari
mesh_terms: D001706:Biopsy; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002066:Busulfan / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D023201:CD40 Ligand / Q000172:deficiency*; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use; D006650:Histocompatibility Testing; D006801:Humans; D053307:Hyper-IgM Immunodeficiency Syndrome, Type 1 / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D008103:Liver Cirrhosis / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D008297:Male; D019653:Myeloablative Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D019653:Myeloablative Agonists; D023201:CD40 Ligand; D003520:Cyclophosphamide; C018404:treosulfan; D002066:Busulfan