{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T09:33:11Z","timestamp":1771493591778,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T00:00:00Z","timestamp":1596672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Busulfan is an alkylating agent routinely used in conditioning regimens prior to allogeneic hematopoietic cell transplantation (HCT) for various nonmalignant disorders, including inborn errors of metabolism. The combination of model-based dosing and therapeutic drug monitoring (TDM) of busulfan pharmacokinetics (PK) to a lower exposure target has the potential to reduce the regimen-related toxicity while opening marrow niches sufficient for engraftment in diseases such as mucopolysaccharidosis type I (MPS I). We present four cases of the severe form of MPS I or Hurler syndrome, demonstrating successful and stable CD14\/15 donor chimerism following the prospective application of model-based dosing and TDM aimed to achieve lower busulfan exposure. All patients received a busulfan-based conditioning regimen with a median cumulative area-under-the-curve (cAUC) target of 63.7 mg h\/L (range, 62.4 to 65.0) in protocol-specific combination of chemotherapeutic regimen. The donor source was unrelated umbilical cord blood for three patients and matched sibling donor bone marrow for one patient. The observed median busulfan cAUC was 66.1 mg h\/L (range, 65.2 to 70.6) and was within 10% of the intended target. Stable, full donor myeloid chimerism was achieved for three patients, while one patient achieved a stable mixed chimerism (76% donor CD14\/15 at 53 months) without a recurring need for enzyme replacement. The normalization of \u03b1-L-iduronidase enzyme levels followed the attainment of successful donor myeloid chimerism in all patients. Regimen-related toxicity remained low with no evidence of acute graft-versus-host disease (GVHD) grades II to IV and chronic GVHD.<\/jats:p>","DOI":"10.3390\/ijms21165634","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T09:41:21Z","timestamp":1596706881000},"page":"5634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Lower Exposure to Busulfan Allows for Stable Engraftment of Donor Hematopoietic Stem Cells in Children with Mucopolysaccharidosis Type I: A Case Report of Four Patients"],"prefix":"10.3390","volume":"21","author":[{"given":"Praveen","family":"Shukla","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, University of California San Francisco, 600 16th Street, Room N474F, San Francisco, CA 94158-0622, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6146-3952","authenticated-orcid":false,"given":"Christopher C.","family":"Dvorak","sequence":"additional","affiliation":[{"name":"Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplant, University of California San Francisco, Benioff Children\u2019s Hospital, 550 16th Street, Floor 4, San Francisco, CA 94143-0434, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janel","family":"Long-Boyle","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, University of California San Francisco, 600 16th Street, Room N474F, San Francisco, CA 94158-0622, USA"},{"name":"Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplant, University of California San Francisco, Benioff Children\u2019s Hospital, 550 16th Street, Floor 4, San Francisco, CA 94143-0434, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6014-7659","authenticated-orcid":false,"given":"Sandhya","family":"Kharbanda","sequence":"additional","affiliation":[{"name":"Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplant, University of California San Francisco, Benioff Children\u2019s Hospital, 550 16th Street, Floor 4, San Francisco, CA 94143-0434, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1182\/bloodadvances.2020001708","article-title":"Hurdles in treating Hurler disease: Potential routes to achieve a \u201creal\u201d cure","volume":"4","author":"Hegeman","year":"2020","journal-title":"Blood Adv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"433","DOI":"10.3389\/fped.2019.00433","article-title":"Early treatment is associated with improved cognition in Hurler syndrome","volume":"7","author":"Tan","year":"2019","journal-title":"Front. 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