Improved transplant survival and long-term disease outcome in children with MHC class II deficiency
Su Han Lum 1, Claire Anderson 1, Peter McNaughton 1, Karin Regine Engelhardt 2, Brigid MacKenzie 1, Helen Watson 3, Hamoud Al-Mousa 4, Waleed Al-Herz 5, Bandar Al-Saud 4, Reem Mohammed 4, Daifulah M Al-Zahrani 6 7, Hamza Ali Alghamdi 8, Loie Goronfolah 7, Zohreh Nademi 1 2, Sahar Habibollah 1, Aisling M Flinn 1, Benjamin Shillitoe 1, Stephen Owens 1, Eleri Williams 1, Marieke Emonts 1 2, Sophie Hambleton 1 2, Mario Abinun 1 2, Terrence Flood 1, Andrew Cant 1, Andrew R Gennery 1 2, Mary Slatter 1 2
Affiliations
Affiliations
- Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
- Blood Sciences, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
- Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
- Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
- Department of Pediatrics, King Abdulaziz Medical City, Jeddah, Saudi Arabia.
- Pediatric Allergy and Immunology, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia; and.
- Pediatric Allergy and Immunology Section, King Fahad Medical City, Riyadh, Saudi Arabia.
Abstract
MHC class II deficiency is a rare, but life-threatening, primary combined immunodeficiency. Hematopoietic cell transplantation (HCT) remains the only curative treatment for this condition, but transplant survival in the previously published result was poor. We analyzed the outcome of 25 patients with MHC class II deficiency undergoing first HCT at Great North Children's Hospital between 1995 and 2018. Median age at diagnosis was 6.5 months (birth to 7.5 years). Median age at transplant was 21.4 months (0.1-7.8 years). Donors were matched family donors (MFDs; n = 6), unrelated donors (UDs; n = 12), and haploidentical donors (HIDs; n = 7). Peripheral blood stem cells were the stem cell source in 68% of patients. Conditioning was treosulfanbased in 84% of patients; 84% received alemtuzumab (n = 14) or anti-thymocyte globulin (n = 8) as serotherapy. With a 2.9-year median follow-up, OS improved from 33% (46-68%) for HCT before 2008 (n = 6) to 94% (66-99%) for HCT after 2008 (n = 19; P = .003). For HCT after 2008, OS according to donor was 100% for MFDs and UDs and 85% for HIDs (P = .40). None had grade III-IV acute or chronic graft-versus-host disease. Latest median donor myeloid and lymphocyte chimerism were 100% (range, 0-100) and 100% (range, 64-100), respectively. Latest CD4+ T-lymphocyte number was significantly lower in transplant survivors (n = 14) compared with posttransplant disease controls (P = .01). All survivors were off immunoglobulin replacement and had protective vaccine responses to tetanus and Haemophilus influenzae. None had any significant infection or autoimmunity. Changing transplant strategy in Great North Children's Hospital has significantly improved outcomes for MHC class II deficiency.
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