{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:28:05Z","timestamp":1791678485728,"version":"4.3.4"},"reference-count":30,"publisher":"American Society of Hematology","issue":"8","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In the ABA2 study, the T-cell costimulation blockade agent, abatacept, was safe and effective in preventing acute graft-versus-host disease (aGVHD) after unrelated-donor hematopoietic cell transplant (HCT), leading to US Food and Drug Administration approval. Here, we performed a determination of abatacept pharmacokinetics (PK), which enabled an examination of how abatacept exposure-response relationships affected clinical outcomes. We performed a population PK analysis of IV abatacept using nonlinear mixed-effect modeling and assessed the association between abatacept exposure and key transplant outcomes. We tested the association between the trough after dose 1 (Ctrough_1) and grade (GR) 2 or 4 aGVHD (GR2-4 aGVHD) through day\u00a0+100. An optimal Ctrough_1 threshold was identified via recursive partitioning and classification tree analysis. This demonstrated that abatacept PK was characterized by a 2-compartment model with first-order elimination. The ABA2 dosing regimen was based on previous work targeting a steady-state abatacept trough of 10 \u03bcg\/mL. However, a higher Ctrough_1 (\u226539 \u03bcg\/mL, attained in \u223c60% of patients on ABA2) was associated with a favorable GR2-4 aGVHD risk (hazard ratio, 0.35; 95% confidence interval, 0.19-0.65; P\u00a0&amp;lt; .001), with a Ctrough_1 &amp;lt;39 \u03bcg\/mL associated with GR2-4 aGVHD risk indistinguishable from placebo (P\u00a0= .37). Importantly, no significant association was found between Ctrough_1 and key safety indicators, including relapse, and cytomegalovirus or Epstein-Barr virus viremia. These data demonstrate that a higher abatacept Ctrough_1 (\u226539 \u03bcg\/mL) was associated with a favorable GR2-4 aGVHD risk, without any observed exposure-toxicity relationships. This trial was registered at www.clinicaltrials.gov as #NCT01743131.<\/jats:p>","DOI":"10.1182\/blood.2023020035","type":"journal-article","created":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T17:13:26Z","timestamp":1686849206000},"page":"700-710","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":19,"title":["Higher abatacept exposure after transplant decreases acute GVHD risk without increasing adverse events"],"prefix":"10.1182","volume":"142","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8296-6412","authenticated-orcid":false,"given":"Takuto","family":"Takahashi","sequence":"first","affiliation":[{"name":"1Division Hematology\/Oncology, Dana-Farber\/Boston Children\u2019s Cancer and Blood Disorders Center, Boston, MA"},{"name":"2Department of Pediatrics, Harvard Medical School, Boston, MA"},{"name":"3Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5458-0712","authenticated-orcid":false,"given":"Mahmoud","family":"Al-Kofahi","sequence":"additional","affiliation":[{"name":"3Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutaz","family":"Jaber","sequence":"additional","affiliation":[{"name":"3Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1498-1001","authenticated-orcid":false,"given":"Brandi","family":"Bratrude","sequence":"additional","affiliation":[{"name":"1Division Hematology\/Oncology, Dana-Farber\/Boston Children\u2019s Cancer and Blood Disorders Center, Boston, MA"},{"name":"2Department of Pediatrics, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla","family":"Betz","sequence":"additional","affiliation":[{"name":"1Division Hematology\/Oncology, Dana-Farber\/Boston Children\u2019s Cancer and Blood Disorders Center, Boston, MA"},{"name":"2Department of Pediatrics, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Suessmuth","sequence":"additional","affiliation":[{"name":"4Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA"},{"name":"5Department of Pediatrics, Emory University, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Yu","sequence":"additional","affiliation":[{"name":"1Division Hematology\/Oncology, Dana-Farber\/Boston Children\u2019s Cancer and Blood Disorders Center, Boston, MA"},{"name":"2Department of Pediatrics, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna S.","family":"Neuberg","sequence":"additional","affiliation":[{"name":"6Department of Data Science, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6321-3834","authenticated-orcid":false,"given":"Sung W.","family":"Choi","sequence":"additional","affiliation":[{"name":"7Department of Pediatrics, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Davis","sequence":"additional","affiliation":[{"name":"8BC Children\u2019s Hospital, University of British Columbia, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Duncan","sequence":"additional","affiliation":[{"name":"1Division Hematology\/Oncology, Dana-Farber\/Boston Children\u2019s Cancer and Blood Disorders Center, Boston, MA"},{"name":"2Department of Pediatrics, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Giller","sequence":"additional","affiliation":[{"name":"9Center for Cancer and Blood Disorders, Children Hospital of Colorado, University of Colorado, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2056-5167","authenticated-orcid":false,"given":"Michael","family":"Grimley","sequence":"additional","affiliation":[{"name":"10Cincinnati Children\u2019s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4538-8817","authenticated-orcid":false,"given":"Andrew C.","family":"Harris","sequence":"additional","affiliation":[{"name":"11Pediatric Bone Marrow Transplant and Cellular Therapy Program, MSK Kids, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Jacobsohn","sequence":"additional","affiliation":[{"name":"12Division of Blood and Marrow Transplantation, Center for Cancer and Blood Disorders, Children\u2019s National Health System, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahal","family":"Lalefar","sequence":"additional","affiliation":[{"name":"13Division of Pediatric Hematology\/Oncology, UCSF Benioff Children\u2019s Hospital Oakland, University of California San Francisco, Oakland, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nosha","family":"Farhadfar","sequence":"additional","affiliation":[{"name":"14Division of Hematology\/Oncology, University of Florida College of Medicine, Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3030-8420","authenticated-orcid":false,"given":"Michael A.","family":"Pulsipher","sequence":"additional","affiliation":[{"name":"15Huntsman Cancer Institute, Spencer Fox Eccles School of Medicine, Primary Children\u2019s Hospital, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Shenoy","sequence":"additional","affiliation":[{"name":"16Division Hematology\/Oncology, Washington University School of Medicine, St Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Petrovic","sequence":"additional","affiliation":[{"name":"17Department of Pediatrics, Seattle Children\u2019s Hospital and Fred Hutch Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0001-6438","authenticated-orcid":false,"given":"Kirk R.","family":"Schultz","sequence":"additional","affiliation":[{"name":"8BC Children\u2019s Hospital, University of British Columbia, Vancouver, 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