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Data from a novel murine HLA\u2010haploidentical HCT model suggested that PTCy has a dose\u2010dependent effect associated with its efficacy in preventing GVHD, including reduced proliferation of conventional CD4\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>\u2212<\/jats:sup>\n                    T\u2010helper cells (Th) at Day 7, followed by the preferential expansion of regulatory CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    T cells (Tregs) at Day 21 after HCT. To better quantify the impact of the PTCy dose, we built a hybrid quantitative systems pharmacology (hybrid systems) model consisting of: (1) simulated pharmacokinetics of PTCy and its metabolites; (2) the donor immune system; and (3) a neural network mapping drug exposure and T\u2010cell profiles to clinical scores of acute GVHD. Data were collected from murine MHC\u2010haploidentical HCT studies of PTCy from 0 to 100\u2009mg\/kg\/day on Days 3 and 4 after transplantation of donor cells. The final model successfully captured time\u2010varying changes in donor Tcytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells (Tc), Th, and Tregs up to Day 21. The clinical score for GVHD was associated with numerous descriptors, with the immediately preceding GVHD score, body weight, PTCy dose, and donor Treg concentration in the blood and in the liver having the greatest contribution. This hybrid systems model quantitatively captures the beneficial impact of PTCy on Tc, Th, Tregs, and acute GVHD after HCT. The mediation through PTCy and metabolite concentrations and Tc, Th, and Treg numbers is underlined, and the model may be further used to refine and improve PTCy regimens.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70252","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T10:24:27Z","timestamp":1776162267000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hybrid Systems Modeling of Donor T\u2010Cell Responses and Graft\u2010Versus\u2010Host\u2010Disease After Posttransplantation Cyclophosphamide Administration"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7428-1349","authenticated-orcid":false,"given":"Hsuan\u2010Hao","family":"Fan","sequence":"first","affiliation":[{"name":"Division of Pharmacokinetics\u2010Pharmacodynamics and Systems Pharmacology, Department of Pharmaceutical Sciences University at Buffalo, SUNY  Buffalo New 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