title: Successful haploidentical PBSCT with subsequent T-cell addbacks in a boy with HyperIgM syndrome presenting as severe congenital neutropenia.
abstract: HIGM syndrome is a group of primary immunodeficiency disorders characterized by recurrent bacterial and opportunistic infections; it is also associated with normal to elevated serum IgM levels and a concomitant deficiency of IgG, IgA, and IgE. In this report, we give account of a boy with X-linked HIGM and a novel Y172C mutation within his CD40LG gene. He presented with severe neutropenia as the dominating symptom. His bone marrow showed maturation arrest at the promyelocyte/myelocyte stage, typical of congenital neutropenia. This boy suffered from life-threatening infections and required high doses of rhG-CSF, and a haploidentical PBSCT was also successfully performed, thus leading to reconstitution of CD40L expression on activated CD4+ T cells (as assessed with flow cytometry six months after the procedure). Two low-dose T-cell addbacks were required to re-establish full donor chimerism and clear CMV reactivation. The report demonstrates that in select cases, alternative donor allogeneic HSCT supported by DLI may be effective in correcting the defect in X-linked HIGM, and HSCT in HIGM children is not necessarily limited to matched sibling donor transplantation.
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jasinska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kalwak
authors.forename: Joanna
authors.initials: J
authors.lastname: Trelinska
authors.forename: Maciej
authors.initials: M
authors.lastname: Borowiec
authors.forename: Barbara
authors.initials: B
authors.lastname: Piatosa
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Zeman
authors.forename: Wojciech
authors.initials: W
authors.lastname: Mlynarski
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D023201:CD40 Ligand / Q000235:genetics*; D000080984:Congenital Bone Marrow Failure Syndromes; D003937:Diagnosis, Differential; D005260:Female; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006579:Heterozygote; D006801:Humans; D053306:Hyper-IgM Immunodeficiency Syndrome / Q000628:therapy*; D007223:Infant; D008297:Male; D009154:Mutation; D009503:Neutropenia / Q000151:congenital* / Q000175:diagnosis; D010375:Pedigree; D035781:Siblings; D014184:Transplantation, Homologous / Q000379:methods
chemical_list: D023201:CD40 Ligand