Hematopoietic stem cell transplantation for CTLA4 deficiency

• Published in: Journal of allergy and clinical immunology Vol. 138; no. 2; pp. 615 - 619.e1
• Main Authors: Slatter, Mary A., MD, Engelhardt, Karin R., PhD, Burroughs, Lauri M., MD, Arkwright, Peter D., DPhil, Nademi, Zohreh, PhD, Skoda-Smith, Suzanne, MD, Hagin, David, PhD, Kennedy, Alan, PhD, Barge, Dawn, PhD, Flood, Terence, MD, Abinun, Mario, PhD, Wynn, Robert F., MD, Gennery, Andrew R., MD, Cant, Andrew J., MD, Sansom, David, PhD, Hambleton, Sophie, DPhil, Torgerson, Troy R., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 01.08.2016
• Subjects: Adolescent; Adult; Age; Allergy and Immunology; Amino Acid Substitution; Arthritis; Bone marrow; Child; Children & youth; CTLA-4 Antigen - deficiency; CTLA-4 Antigen - genetics; CTLA-4 Antigen - immunology; Diabetes; Female; Frameshift Mutation; Haploinsufficiency - genetics; Haploinsufficiency - immunology; Hematopoietic Stem Cell Transplantation; Humans; Immune System Diseases - genetics; Immune System Diseases - immunology; Immune System Diseases - therapy; Immunoglobulins; Inflammatory bowel disease; Ligands; Lung diseases; Lymphoma; Male; Mortality; Mutation; Mutation, Missense; Neutropenia; Parenteral nutrition; Patients; Pediatrics; Skin; Stem cells; Steroids; Transplants & implants; Treatment Outcome; United Kingdom > UK
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2016.01.045

Patient 4 (sibling to patient 3) was well until he presented with inflammatory colitis and Hodgkin lymphoma (inguinal and para-aortic region) at age 16 years. Because of his sibling's history, CTLA4 haploinsufficiency was confirmed by both genetic and protein level testing, the only patient in this cohort to have an identified mutation before HSCT. In summary, 4 of 8 patients experienced GvHD despite having well-matched donors and receiving alemtuzumab in 3 out of 4 cases.\n9 (5.4-16.8)IgA 0.27 (0.74-2.61)IgM 0.84 (0.40-1.95)Preimmunoglobulin therapyPre-RTX 23 y Interstitial lung disease ("nodular lymphoid hyperplasia") Transverse myelitis Recurrent white matter and brainstem lesions with oligoclonal bands and elevated IgG index Arthritis Father:ITPSister:Patient no. 7 Table I Patients' characteristics ABVD, Adriamcyin (Doxorubicin), bleomycin, vinblastine, dacarbazine; naive CD4, CD3+CD4+CD27+CD45RA+; naive CD8, CD3+CD4-CD27+CD45RA+; Euronet PHL-C1, Euronet pediatric Hodgkin lymphoma-C1; F, female; IDDM, insulin-dependent diabetes mellitus; ITP, idiopathic thrombocytopenic purpura; M, male; NK, natural killer; PN, parenteral nutrition; RTX, rituximab.