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Supportive care alone is linked to unfavorable outcomes, necessitating allogeneic hematopoietic cell transplantation (HCT) as a curative option. Although myeloablative conditioning is recommended for HCT, concerns remain regarding its toxicity. We reviewed ten patients with XHIGM who underwent HCT using reduced-toxicity conditioning (RTC) at our institution between 2010 and 2024. All patients underwent HCT by 5\u00a0years of age (range: 2\u20135\u00a0years; median: 3\u00a0years). Donor sources included unrelated bone marrow, unrelated cord blood, and haploidentical-related donors. Conditioning primarily consisted of fludarabine and busulfan (target area under the curve: 60\u201365\u00a0mg\/L\u00b7h), with low-dose total body irradiation (TBI) administered in five patients. Two patients experienced graft failure, requiring a second transplantation, and one died from post-transplant complications. The remaining nine patients survived. The 5-year overall survival rate was 88.9%; the 5-year graft-versus-host disease-free, relapse-free, and second transplantation-free survival rate was 67.5%. The addition of low-dose TBI to fludarabine\/busulfan was associated with favorable long-term donor chimerism, although this finding should be considered hypothesis-generating. RTC may represent a feasible conditioning strategy for XHIGM.\n                  <\/jats:p>","DOI":"10.1007\/s12185-026-04245-8","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:43:05Z","timestamp":1783420985000},"page":"704-712","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Allogeneic hematopoietic cell transplantation with reduced-toxicity conditioning for X-linked hyper-IgM syndrome"],"prefix":"10.1007","volume":"124","author":[{"given":"Ryosuke","family":"Wakatsuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Hoshino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Ishibashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryohei","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Magara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Tomomasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyogo","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Kamiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Isoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohsuke","family":"Imai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Kajiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Morio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Takagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8696-9378","authenticated-orcid":false,"given":"Hirokazu","family":"Kanegane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"4245_CR1","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1126\/science.7679801","volume":"259","author":"RC Allen","year":"1993","unstructured":"Allen RC, Armitage RJ, Conley ME, Rosenblatt H, Jenkins NA, Copeland NG, et al. 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This study was performed in accordance with the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of the Institute of Science Tokyo (G2019-004).","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}