{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:14:34Z","timestamp":1785413674793,"version":"3.56.0"},"reference-count":18,"publisher":"Rockefeller University Press","issue":"5","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9,7]]},"abstract":"<jats:p>Mendelian susceptibility to mycobacterial disease (MSMD) is a rare group of inborn errors of immunity associated with significant morbidity due to mycobacterial infections. Hematopoietic stem cell transplantation (HSCT) is a curative option; however, persistent infections and high levels of interferon-\u03b3 (IFN-\u03b3) create a hostile environment for stem cell proliferation and can mediate graft rejection. We describe the outcome of children with MSMD due to IFN-\u03b3 receptor and interleukin-12 (IL-12) defects who underwent HSCT in our unit from December 2015 to December 2023. We collected the data retrospectively from a review of patient charts and analyzed the outcomes. Seven children underwent eight procedures, including four with IFN-\u03b3 defects and three with IL-12 defects. The male-to-female ratio was 1.6:1, and the median age at HSCT was 4.5 years. Five received haploidentical HSCT, and two underwent matched family donor transplants; 75% used peripheral blood stem cells. IL-12\u2013deficient cases engrafted well with fludarabine\/treosulfan\u2013based conditioning, whereas IFN-\u03b3\u2013deficient cases fared better with fludarabine\/treosulfan\/thiotepa-based conditioning due to a higher rejection risk. Acute graft-versus-host disease (GVHD) (grade 1\u20132, skin\/gut) occurred in two children: one developed chronic liver GVHD after donor lymphocyte infusion. Cytomegalovirus reactivation occurred in four cases, which responded to ganciclovir or cidofovir. One primary graft failure was rescued with a second HSCT; one secondary graft failure led to death from invasive fungal infection. At a median follow-up of 8 years, the overall survival was 87%. One survivor has ongoing seizures, aggressive behavior, and endocrine dysfunctions requiring supportive care. HSCT is a curative option for children with MSMD. However, we need to understand gene mutation and individualize the approach to preparation and conditioning regimens to help optimize the outcome.<\/jats:p>","DOI":"10.70962\/jhi.20250264","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:21:53Z","timestamp":1782195713000},"update-policy":"https:\/\/doi.org\/10.70962\/jhi.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Tailored conditioning for hematopoietic stem cell transplantation in children with Mendelian susceptibility to mycobacterial disease: A tale of two pathways for IFN-\u03b3 and IL-12 defects"],"prefix":"10.70962","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9486-7219","authenticated-orcid":true,"given":"Kavitha","family":"Ganesan","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ew45630","id-type":"ROR","asserted-by":"publisher"}],"name":"Blood and Marrow Transplantation Unit, Apollo Hospitals 1 Department of Pediatric 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