{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:53:34Z","timestamp":1784098414977,"version":"3.55.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Post-transplant cyclophosphamide (PTCy) is increasingly used for graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (alloHCT), across both haploidentical and HLA-matched donor settings. However, PTCy-based alloHCT is associated with post-transplant cytokine release syndrome (CRS), an early inflammatory toxicity driven by donor T-cell alloreactivity. Mechanistically distinct from chimeric antigen receptor (CAR) T-cell therapy-associated CRS, post-transplant CRS is driven by conditioning-induced tissue injury and donor T-cell alloreactivity. The incidence of CRS varies by donor type, occurring in approximately 10% of matched sibling, 20 to 75% of matched unrelated, and 80 to 90% of haploidentical donor transplants. Risk factors include peripheral blood grafts, HLA class II mismatch, and high-intensity conditioning. Severe CRS has been linked to delayed engraftment, increased acute GVHD, decreased chronic GVHD, and may contribute to non-relapse mortality through mechanisms such as third-spacing, infectious complications, and neurologic toxicity. Tocilizumab is effective for CRS treatment, though its impact on subsequent GVHD risk requires further study. Early initiation of calcineurin inhibitors and use of pre-transplant anti-thymocyte globulin have shown promise in reducing CRS incidence. CRS-associated neurotoxicity, resembling immune effector cell-associated neurotoxicity syndrome (ICANS), is increasingly recognized, particularly among patients with severe CRS, and can result in delayed, fatal encephalopathy. In summary, post-transplant CRS is a clinically significant complication of PTCy-based alloHCT. Optimizing prophylaxis and management strategies is essential to mitigate its impact on transplant outcomes.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1642583","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T04:25:02Z","timestamp":1777868702000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cytokine release syndrome after allogeneic hematopoietic stem cell transplantation using posttransplant cyclophosphamide: current understanding and management"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiasheng","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Medicine, The Ohio State University Comprehensive Cancer Center","place":["Columbus, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirti","family":"Arora","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cleveland Clinic Akron General","place":["Akron, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"de Lima","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, The Ohio State University Comprehensive Cancer Center","place":["Columbus, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1172\/jci124218","article-title":"Post-transplantation cyclophosphamide prevents graft-versus-host disease by inducing alloreactive T cell dysfunction and suppression","volume":"129","author":"Wachsmuth","year":"2019","journal-title":"J Clin Invest"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2008.03.005","article-title":"HLA-haploidentical bone marrow transplantation for hematologic Malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide","volume":"14","author":"Luznik","year":"2008","journal-title":"Biol Blood Marrow Transplant"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1200\/jco-25-00856","article-title":"Post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis after mismatched unrelated donor peripheral blood stem cell transplantation","volume":"43","author":"Al Malki","year":"2025","journal-title":"J Clin Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2215943","article-title":"Post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis","volume":"388","author":"Bolanos-Meade","year":"2023","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1053\/bbmt.2002.v8.pm12171484","article-title":"Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide","volume":"8","author":"O\u2019Donnell","year":"2002","journal-title":"Biol Blood Marrow Transplant"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.02.001","article-title":"Bone marrow compared with peripheral blood stem cells for haploidentical transplantation with a nonmyeloablative conditioning regimen and post-transplantation cyclophosphamide","volume":"20","author":"Castagna","year":"2014","journal-title":"Biol Blood Marrow Transplant"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.10.008","article-title":"High fever occurring 4 to 5 days post-transplant of haploidentical bone marrow or peripheral blood stem cells after reduced-intensity conditioning associated with the use of post-transplant cyclophosphamide as prophylaxis for graft-versus-host disease","volume":"21","author":"O\u2019Donnell","year":"2015","journal-title":"Biol Blood Marrow Transplant"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.03.003","article-title":"Peripheral blood hematopoietic stem cells for transplantation of hematological diseases from related, haploidentical donors after reduced-intensity conditioning","volume":"20","author":"Raj","year":"2014","journal-title":"Biol Blood Marrow Transplant"},{"key":"B9","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1002\/hon.2772","article-title":"Cytokine release syndrome after allogeneic stem cell transplantation with posttransplant cyclophosphamide","volume":"38","author":"Solan","year":"2020","journal-title":"Hematol Oncol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/cells12162049","article-title":"Autoimmune limbic encephalitis in patients with hematologic Malignancies after haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide","volume":"12","author":"Heo","year":"2023","journal-title":"Cells"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-198502000-00019","article-title":"Drug-induced tolerance to allografts in mice. 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