{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T02:45:10Z","timestamp":1761101110517,"version":"build-2065373602"},"reference-count":15,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,4,12]],"date-time":"2012-04-12T00:00:00Z","timestamp":1334188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2012,5]]},"abstract":"Study Objectives<\/jats:title>To determine the frequency of sinusoidal obstructive syndrome (SOS<\/jats:styled-content>) in patients undergoing allogeneic hematopoietic cell transplantation who received graft\u2010versus\u2010host disease (GVHD<\/jats:styled-content>) prophylaxis with sirolimus and tacrolimus, and to assess whether the occurrence of SOS<\/jats:styled-content> correlates with immunosuppressant levels.<\/jats:p><\/jats:sec>Design<\/jats:title>Retrospective cohort study.<\/jats:p><\/jats:sec>Setting<\/jats:title>Hematopoietic cell transplant unit at an academic medical center.<\/jats:p><\/jats:sec>Patients<\/jats:title>Fifty\u2010nine adults who received myeloablative preparative regimens for transplantation of any hematologic malignancy and received sirolimus and tacrolimus for GVHD<\/jats:styled-content> prophylaxis between January 1, 2007, and May 1, 2009; all donors and transplant recipients were human leukocyte antigen (HLA<\/jats:styled-content>) matched for at least HLA<\/jats:styled-content>\u2010A, \u2010B, \u2010C, and \u2010DRB<\/jats:styled-content>1.<\/jats:p><\/jats:sec>Measurements and Main Results<\/jats:title>The primary outcome was the occurrence of SOS<\/jats:styled-content> after hematopoietic cell transplantation. Plasma concentrations of sirolimus and tacrolimus and the summative levels of sirolimus and tacrolimus were then compared in patients who developed SOS<\/jats:styled-content> with those who did not develop SOS<\/jats:styled-content>. Trough levels were measured from blood samples collected 30\u201360\u00a0minutes before the morning doses of sirolimus and tacrolimus on days 0\u201335, or until the development of SOS<\/jats:styled-content>. Of the 59 patients, 12 (20%) developed SOS<\/jats:styled-content>. The mean sirolimus level was significantly higher in patients who developed SOS<\/jats:styled-content> relative to those who did not develop SOS<\/jats:styled-content> (10.5 vs 8.7\u00a0ng\/ml, p=0.003). The mean summative trough level of sirolimus and tacrolimus was also significantly higher in those who developed SOS<\/jats:styled-content> compared with those who did not (19.7 vs 17.1\u00a0ng\/ml, p=0.003). The mean \u00b1 SD<\/jats:styled-content> time to the occurrence of SOS<\/jats:styled-content> was 28 \u00b1 8.7\u00a0days. The median time to death was 101\u00a0days for patients who developed SOS<\/jats:styled-content> compared with 433\u00a0days for patients who did not develop SOS<\/jats:styled-content> (p=0.002).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Sirolimus plasma concentration may correlate with the development of delayed SOS<\/jats:styled-content>; however, further research is needed to prospectively evaluate the role of sirolimus exposure in the pathogenesis of SOS<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/j.1875-9114.2012.01034.x","type":"journal-article","created":{"date-parts":[[2012,9,5]],"date-time":"2012-09-05T03:55:20Z","timestamp":1346817320000},"page":"441-445","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Possible Correlation of Sirolimus Plasma Concentration with Sinusoidal Obstructive Syndrome of the Liver in Patients Undergoing Myeloablative Allogeneic Hematopoietic Cell Transplantation"],"prefix":"10.1002","volume":"32","author":[{"given":"Patrick J.","family":"Kiel","sequence":"first","affiliation":[{"name":"Department of Pharmacy Indiana University Simon Cancer Center Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig A.","family":"Vargo","sequence":"additional","affiliation":[{"name":"College of Pharmacy Purdue University West Lafayette Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gourang P.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Rush University Medical Center Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsay L.","family":"Rosenbeck","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Indiana University Simon Cancer Center Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shivani","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Medicine Bone Marrow and Stem Cell Transplantation Indiana University School of Medicine Indianapolis 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