{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:54:44Z","timestamp":1784782484501,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Study Objective<\/jats:title><jats:p>Alemtuzumab is a monoclonal antibody that targets the cell surface antigen CD52 on lymphocytes. Although it is used for the treatment of hematologic malignancies, such as chronic lymphocytic leukemia, and incorporated into many hematopoietic stem cell transplant (HSCT) conditioning regimens, few studies have evaluated the pharmacology of alemtuzumab in adult patients with sickle cell disease (SCD). We therefore examined the pharmacokinetics (PK) and pharmacodynamics (PD) of alemtuzumab in adults with SCD who received a matched related donor HSCT to determine if the clearance of alemtuzumab affects transplant outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>PK and PD analysis of patient data from a single\u2010center clinical trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Clinical research center.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>Twenty\u2010two adult patients with SCD who received one of two nonmyeloablative allogeneic HSCT regimens: alemtuzumab and total body irradiation (Alem\u2010TBI) or pentostatin, cyclophosphamide, alemtuzumab, and total body irradiation (Pento\u2010Cy\u2010Alem\u2010TBI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements and Main Results<\/jats:title><jats:p>Alemtuzumab serum concentrations, absolute lymphocyte counts, T\u2010cell (CD3), and myeloid (CD14\/15) chimerism were collected at distinct time points and analyzed. A semi\u2010mechanistic PK population model was built to understand inter\u2010individual differences in pharmacology. Alemtuzumab was detectable up to 28\u00a0days post\u2010HSCT. The mean alemtuzumab level 7\u00a0days after transplant for patients on Alem\u2010TBI was 818\u00a0ng\/ml, significantly lower than the mean level of 1502\u00a0ng\/ml for patients on Pento\u2010Cy\u2010Alem\u2010TBI (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001), but this difference decreased as time progressed. The clearance of alemtuzumab was linear, and the half\u2010life was longer in the Pento\u2010Cy\u2010Alem\u2010TBI group (average half\u2010life\u00a0=\u00a061.1\u00a0h) compared to the Alem\u2010TBI group (average half\u2010life\u00a0=\u00a044.1\u00a0h) (<jats:italic>p\u00a0<\/jats:italic>&lt;\u00a00.001). The CD3 chimerism at 2 and 4\u00a0months after transplant positively correlated with alemtuzumab levels collected on day 14 after transplant (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.40 and <jats:italic>p\u00a0<\/jats:italic>=\u00a00.004 at 2\u00a0months, <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.36 and <jats:italic>p<\/jats:italic>\u00a0=\u00a00.005 at 4\u00a0months), but this significance was lost by 6 months after HSCT. No correlation was seen between alemtuzumab levels and CD14\/15 chimerism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Between 2 and 4 months after transplant, higher alemtuzumab levels measured 14 days after transplant correlated with patients having better engraftment, suggesting more lymphodepletion may be needed to reduce graft failure in these two non\u2010myeloablative matched related donor HSCT regimens.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2641","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T18:59:53Z","timestamp":1634756393000},"page":"14-22","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Alemtuzumab clearance, lymphocyte count, and T\u2010cell chimerism after hematopoietic stem cell transplant in sickle cell disease"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3800-1941","authenticated-orcid":false,"given":"Dana","family":"Furstenau","sequence":"first","affiliation":[{"name":"Cellular and Molecular Therapeutics Branch National Heart, Lung, and Blood Institute National Institutes of Health Bethesda Maryland USA"},{"name":"Division of Hematology Department of Pediatrics Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody J.","family":"Peer","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Program National Cancer Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Clinical Center Pharmacy Department National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Uchida","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Therapeutics Branch National Heart, Lung, and Blood Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Tisdale","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Therapeutics Branch National Heart, Lung, and Blood Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver Morgan","family":"Hall","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Program National Cancer Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Figg","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Program National Cancer Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Therapeutics Branch National Heart, Lung, and Blood Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.10"},{"key":"e_1_2_7_3_1","unstructured":"American Society of Hematology State of Sickle Cell DiseaseAmerican Society of Hematology.https:\/\/www.scdcoalition.org\/pdfs\/ASHStateofSickleCellDisease2016Report.pdf. 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