{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:30:15Z","timestamp":1790652615947,"version":"4.1.0"},"posted":{"date-parts":[[2025,2,26]]},"group-title":"Oncology","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,2,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Successful hematopoietic cell transplant requires immunosuppression to prevent graft-versus-host disease (GVHD), a lethal, T-cell-mediated post-transplant complication. The phase 3 BMT CTN 1703 trial demonstrated superior GVHD-free\/relapse-free survival for post-transplant cyclophosphamide (PT-Cy)-based GVHD prophylaxis versus tacrolimus\/methotrexate (Tac\/MTX), but did not improve overall survival. To compare T-cell biology between GVHD prophylaxis regimens, 324 patients were co-enrolled onto BMT CTN 1801 (\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03959241\">NCT03959241<\/jats:ext-link>\n                  ). We quantified T-cell immune reconstitution using multi-modal analysis, including T-cell receptor (TCR) sequencing of 2,359 longitudinal samples (180,432,350 T-cells). Compared to Tac\/MTX, PT-Cy was associated with an early, substantial reduction in TCR diversity that was sustained for 2 years. PT-Cy led to a T-cell reconstitution bottleneck, including reduced thymic output and virus-associated TCRs. Decreased D+14 TCR diversity predicted prevention of chronic GVHD, but also correlated with increased moderate-to-severe infections. This study reveals how distinct immunosuppression strategies have significant effects on the global immune repertoire, underpinning post-transplant clinical outcomes.\n                <\/jats:p>","DOI":"10.1101\/2025.02.25.25322901","type":"posted-content","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T01:50:19Z","timestamp":1740621019000},"source":"Crossref","is-referenced-by-count":10,"title":["Graft-versus-host disease prophylaxis shapes T cell biology and immune reconstitution after hematopoietic cell transplant"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0690-2390","authenticated-orcid":false,"given":"Steven 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