Unrelated Hematopoietic Cell Transplantation in a Patient with Combined Immunodeficiency with Granulomatous Disease and Autoimmunity Secondary to RAG Deficiency
- 333 Downloads
The use of HLA-identical hematopoietic stem cell transplantation (HSCT) demonstrates overall survival rates greater than 75 % for T-B-NK+ severe combined immunodeficiency secondary to pathogenic mutation of recombinase activating genes 1 and 2 (RAG1/2). Limited data exist regarding the use of HSCT in patients with hypomorphic RAG variants marked by greater preservation of RAG activity and associated phenotypes such as granulomatous disease in combination with autoimmunity. We describe a 17-year-old with combined immunodeficiency and immune dysregulation characterized by granulomatous lung disease and autoimmunity secondary to compound heterozygous RAG mutations. A myeloablative reduced toxicity HSCT was completed using an unrelated bone marrow donor. With the increasing cases of immune dysregulation being discovered with hypomorphic RAG variants, the use of HSCT may advance to the forefront of treatment. This case serves to discuss indications of HSCT, approaches to preparative therapy, and the potential complications in this growing cohort of patients with immune dysregulation and RAG deficiency.
KeywordsRAG deficiency primary immunodeficiency immune dysregulation autoimmunity bone marrow transplantation
Compliance with Ethical Standards
Written consent was obtained from the patient for participation in an NIAID IRB-approved research protocol. Written consent was obtained from the patient for participation in CHOC Children’s Hospital IRB-approved research protocols.
Conflict of Interest
The authors declare that they have no competing interests.
This work was supported in part by funds from the Intramural Research Program of the National Institute of Allergy and Infectious Disease (NIAID), National Institute of Health (NIH).
- 3.Dvorak CC, Hassan A, Slatter MA, Honig M, Lankester AC, Buckley RH, et al. Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency. J Allergy Clin Immunol. 2014;134(4):935–43. e15.CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Dominietto A, Raiola AM, van Lint MT, Lamparelli T, Gualandi F, Berisso G, et al. Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft-versus-host disease, donor type, cytomegalovirus infections and cell dose. Br J Haematol. 2001;112(1):219–27.CrossRefPubMedGoogle Scholar
- 19.Haen SP, Schumm M, Faul C, Kanz L, Bethge WA, Vogel W. Poor graft function can be durably and safely improved by CD34 + −selected stem cell boosts after allogeneic unrelated matched or mismatched hematopoietic cell transplantation. J Cancer Res Clin Oncol. 2015;141(12):2241–51.CrossRefPubMedGoogle Scholar
- 24.Morillo-Gutierrez B, Beier R, Rao K, Burroughs L, Schulz A, Ewins AM, et al. Treosulfan based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicenter experience. Blood 2016.Google Scholar