{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:30:56Z","timestamp":1788582656586,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T00:00:00Z","timestamp":1715385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nonmyeloablative, matched sibling donor hematopoietic stem cell transplantation with alemtuzumab\/total body irradiation (TBI) conditioning is a curative therapy with low toxicity for adults with sickle cell disease (SCD). However, relatively low donor chimerism levels and graft rejection remain important challenges. We hypothesized that adding azathioprine\/hydroxyurea preconditioning will improve donor chimerism levels and reduce graft failure rate. In this prospective cohort study, we enrolled consecutive adult patients with SCD undergoing matched sibling donor transplantation at the Amsterdam UMC. Patients received azathioprine 150\u2009mg\/day and hydroxyurea 25\u2009mg\/kg\/day for 3\u2009months prior to alemtuzumab 1\u2009mg\/kg and 300\u2009cGy TBI conditioning. Twenty patients with SCD (median age 26\u2009years [range 19\u201349], 13 females) were transplanted. Median follow\u2010up was 46.0\u2009months (IQR 21.8\u201357.9). One\u2010year overall survival and event\u2010free survival (graft failure or death) were both 95% (95% confidence interval 86\u2013100). Mean donor myeloid and T\u2010cell chimerism 1\u2010year post\u2010transplant were 95.2% (SD \u00b110.6) and 67.3% (\u00b115.3), respectively. One patient (5%) experienced graft failure without autologous regeneration, resulting in infections and death. All other patients had a corrected SCD phenotype and were able to discontinue sirolimus. Three patients were successfully treated with alemtuzumab (1\u2009mg\/kg) after the transplant because of declining donor chimerism and cytopenias to revert impending graft rejection. Toxicity was mostly related to sirolimus and alemtuzumab. One patient developed steroid\u2010responsive grade II intestinal acute graft\u2010versus\u2010host disease. Collectively, preconditioning with azathioprine\/hydroxyurea prior to nonmyeloablative matched sibling donor transplantation resulted in excellent event\u2010free survival and robust donor T\u2010cell chimerism, enabling the successful withdrawal of sirolimus. <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>: NCT05249452.<\/jats:p>","DOI":"10.1002\/ajh.27360","type":"journal-article","created":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T08:53:15Z","timestamp":1715417595000},"page":"1523-1531","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Azathioprine\/hydroxyurea preconditioning prior to nonmyeloablative matched sibling donor hematopoietic stem cell transplantation in adults with sickle cell disease: A prospective observational cohort study"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0905-1907","authenticated-orcid":false,"given":"Elisabeth","family":"Dovern","sequence":"first","affiliation":[{"name":"Department of Hematology Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4506-8186","authenticated-orcid":false,"given":"Mesire","family":"Aydin","sequence":"additional","affiliation":[{"name":"Department of Hematology Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette D.","family":"Hazenberg","sequence":"additional","affiliation":[{"name":"Department of Hematology Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9726-9943","authenticated-orcid":false,"given":"Man Wai","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Hematology Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth M.","family":"Suijk","sequence":"additional","affiliation":[{"name":"Department of Hematology Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerianne M.","family":"Hoogendoorn","sequence":"additional","affiliation":[{"name":"Department of Hematology Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte F. J.","family":"Van Tuijn","sequence":"additional","affiliation":[{"name":"Department of Hematology Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Louis","family":"Kerkhoffs","sequence":"additional","affiliation":[{"name":"Department of Hematology HagaZiekenhuis  The Hague The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline E.","family":"Rutten","sequence":"additional","affiliation":[{"name":"Department of Hematology Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sacha S.","family":"Zeerleder","sequence":"additional","affiliation":[{"name":"Department of Hematology, Division of Internal Medicine Luzerner Kantonsspital  Lucerne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josu","family":"de la Fuente","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, St. Mary's Hospital Imperial Healthcare NHS Trust  London UK"},{"name":"Department of Immunology and Inflammation Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4426-5743","authenticated-orcid":false,"given":"Bart J.","family":"Biemond","sequence":"additional","affiliation":[{"name":"Department of Hematology Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-930X","authenticated-orcid":false,"given":"Erfan","family":"Nur","sequence":"additional","affiliation":[{"name":"Department of Hematology Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Blood Cell Research Sanquin Research  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.06.036673"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26063"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.15374"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.213207"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-10-745711"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06592.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27297"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2021.09.009"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0904971"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17311"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27295"},{"issue":"14","key":"e_1_2_9_13_1","first-page":"1185","article-title":"Baseline TP53 mutations in adults with SCD developing myeloid malignancy following hematopoietic cell transplantation","volume":"135","author":"Ghannam JY","year":"2020","journal-title":"Blood"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11113160"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0325-6"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1083-8791(03)00192-7"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000001873"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-08-2800"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040297"},{"key":"e_1_2_9_20_1","volume-title":"Alemtuzumab Reverses Secondary Graft Rejection in Allogeneic Stem Cell Transplantation in Patients with Sickle Cell Disease","author":"Nur E","year":"2023"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsigen.2009.10.007"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25040765"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1927.10502953"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2015.09.001"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1212007"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.7192"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2013.39"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-021-01277-y"},{"key":"e_1_2_9_29_1","article-title":"Pre\u2010transplantation suppression of Haemopoiesis is associated with a high rate of macrophage activation syndrome in Ptcy Haploidentical transplantation for Haemoglobinopathies. 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