{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:41:33Z","timestamp":1791520893166,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T00:00:00Z","timestamp":1704153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100011541","name":"Division of Cancer Epidemiology and Genetics","doi-asserted-by":"publisher","award":["K12CA237806"],"award-info":[{"award-number":["K12CA237806"]}],"id":[{"id":"10.13039\/100011541","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Transplant\u2010associated thrombotic microangiopathy (TA\u2010TMA) is a common, severe complication of allogeneic hematopoietic cellular therapy (HCT). Even when treated in many studies, morbidity and mortality rates are high. This prospective single\u2010institution cohort study serially enrolled all allogeneic HCT recipients from August 2019\u2013August 2022. Patients were universally screened for TA\u2010TMA and intermediate and high\u2010risk patients were immediately treated with eculizumab. Sub\u2010distribution cox\u2010proportional hazards models\u00a0were used to identify sub\u2010distribution hazard ratios (sHR)\u00a0 for multi\u2010organ dysfunction (MOD) and non\u2010relapse\u2010related mortality (NRM). Of 136 patients, 36 (26%) were diagnosed with TA\u2010TMA and 21\/36 (58%) developed MOD, significantly more than those without TA\u2010TMA, (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001). Of those with TA\u2010TMA, 18 (50%) had high\u2010risk TA\u2010TMA (HR\u2010TA\u2010TMA), 11 (31%) had intermediate\u2010risk TA\u2010TMA (IR\u2010TA\u2010TMA), and 8 (22%) had standard risk (SR\u2010TA\u2010TMA). Twenty\u2010six were treated with eculizumab (1\/8 SR, 7\/11 IR, and 18\/18 HR). Elevated D\u2010dimer predicted the development of MOD (sHR 7.6, 95% confidence interval [CI] 1.8\u201332.3). Children with concurrent sinusoidal obstructive syndrome (SOS) and TA\u2010TMA had an excess risk of MOD of 34% and data supported a biologic interaction. The adjusted NRM risk was significantly higher in the TA\u2010TMA patients (sHR 10.54, 95% CI 3.8\u201329.2, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001), despite prompt treatment with eculizumab. Significant RF for NRM in TA\u2010TMA patients included SOS (HR 2.89, 95% 1.07\u20137.80) and elevated D\u2010dimer (HR 3.82, 95% CI 1.14\u201312.84). An unrelated donor source and random urine protein to creatine ratio\u2009\u22652\u2009mg\/mg were significantly associated with no response to eculizumab (odds ratio 15, 95% CI 2.0\u2013113.6 and OR 6.5, 95% CI 1.1\u201338.6 respectively). TA\u2010TMA was independently associated with NRM despite early diagnosis and treatment with eculizumab in this large pediatric transplant cohort. Prognostic implications of D\u2010dimer in TA\u2010TMA merit further investigation as this is a readily accessible biomarker. Concurrent SOS is an exclusion criterion of many ongoing clinical trials, but these data highlight these patients could benefit from novel therapeutic approaches. Multi\u2010institutional clinical trials are needed to understand the impact of TA\u2010TMA\u2010targeted therapies.<\/jats:p>","DOI":"10.1002\/ajh.27186","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T16:29:03Z","timestamp":1704212943000},"page":"370-379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["<scp>D<\/scp>\u2010dimer and sinusoidal obstructive syndrome\u2010novel poor prognostic features of thrombotic microangiopathy in children after hematopoietic cellular therapy in a single institution prospective cohort study"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4565-6399","authenticated-orcid":false,"given":"Michelle L.","family":"Schoettler","sequence":"first","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Pediatric Hematopoietic Cellular Therapy  Atlanta Georgia 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Center, Children's Healthcare of Atlanta, Pediatric Hematopoietic Cellular Therapy  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuri","family":"Hudson","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Pediatric Hematopoietic Cellular Therapy  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Obordo","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Pediatric Hematopoietic Cellular Therapy  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanmuganathan","family":"Chandrakasan","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Pediatric Hematopoietic Cellular Therapy  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhag","family":"Parikh","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Pediatric Hematopoietic Cellular Therapy  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Watkins","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Pediatric Hematopoietic Cellular Therapy  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Stenger","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Pediatric Hematopoietic Cellular Therapy  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muna","family":"Qayed","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood 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