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However, gaps remain in managing refractory CMV and optimizing virus\u2010specific cellular therapy (VST). We conducted a comparative analysis of how timing and dosing of immunosuppressive agents, including post\u2010transplant cyclophosphamide (PT\u2010Cy), corticosteroids, mycophenolate mofetil (MMF), and calcineurin inhibitors (CNIs), shape CMV\u2010specific T\u2010cell polyfunctionality. CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell responses (IFN\u2010\u03b3 plus \u2265\u20091 functional marker) were assessed following pp65 stimulation within 100\u2009days post\u2010HCT in the pre\u2010 and post\u2010letermovir era. Among 243 patients, 31% exhibited polyfunctional CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    responses. PT\u2010Cy did not significantly impair T\u2010cell functionality. Cyclosporine was associated with higher frequencies of polyfunctional T cells compared to tacrolimus, even at concentrations above the therapeutic range. Intermediate (\u2265\u20090.5\u2009mg\/kg) and high\u2010dose (\u2265\u20091\u2009mg\/kg) corticosteroids, especially within 2\u20134\u2009weeks before testing, significantly suppressed T\u2010cell responses, though rapid tapering preserved function. Prolonged administration of MMF (\u2265\u20092000\u2009mg) diminished T\u2010cell polyfunctionality. These findings provide novel insights into the importance of timing and dosing of the immunosuppressive effects of PT\u2010Cy, corticosteroids, MMF and CNIs on CMV\u2010specific immunity. Adjusting immunosuppression in specific time windows may improve the management of refractory CMV infections and optimize VST in HCT recipients.\n                  <\/jats:p>","DOI":"10.1002\/ajh.70152","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T12:41:04Z","timestamp":1764592864000},"page":"255-268","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["New Insights Into Factors Shaping\n                    <scp>CMV<\/scp>\n                    \u2010Specific T\u2010Cell Polyfunctionality After Hematopoietic Cell Transplantation"],"prefix":"10.1002","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7752-5839","authenticated-orcid":false,"given":"Alicja","family":"Sadowska\u2010Klasa","sequence":"first","affiliation":[{"name":"Fred Hutchinson Cancer Center  Seattle Washington USA"},{"name":"Medical University of Gdansk  Gdansk 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