{"doi":"10.1002/ajh.27186","title":"<scp>D</scp>‐dimer and sinusoidal obstructive syndrome‐novel poor prognostic features of thrombotic microangiopathy in children after hematopoietic cellular therapy in a single institution prospective cohort study","abstract":"Transplant-associated thrombotic microangiopathy (TA-TMA) 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-institution cohort study serially enrolled all allogeneic HCT recipients from August 2019-August 2022. Patients were universally screened for TA-TMA and intermediate and high-risk patients were immediately treated with eculizumab. Sub-distribution cox-proportional hazards models were used to identify sub-distribution hazard ratios (sHR) for multi-organ dysfunction (MOD) and non-relapse-related mortality (NRM). Of 136 patients, 36 (26%) were diagnosed with TA-TMA and 21/36 (58%) developed MOD, significantly more than those without TA-TMA, (p < .0001). Of those with TA-TMA, 18 (50%) had high-risk TA-TMA (HR-TA-TMA), 11 (31%) had intermediate-risk TA-TMA (IR-TA-TMA), and 8 (22%) had standard risk (SR-TA-TMA). Twenty-six were treated with eculizumab (1/8 SR, 7/11 IR, and 18/18 HR). Elevated D-dimer predicted the development of MOD (sHR 7.6, 95% confidence interval [CI] 1.8-32.3). Children with concurrent sinusoidal obstructive syndrome (SOS) and TA-TMA had an excess risk of MOD of 34% and data supported a biologic interaction. The adjusted NRM risk was significantly higher in the TA-TMA patients (sHR 10.54, 95% CI 3.8-29.2, p < .0001), despite prompt treatment with eculizumab. Significant RF for NRM in TA-TMA patients included SOS (HR 2.89, 95% 1.07-7.80) and elevated D-dimer (HR 3.82, 95% CI 1.14-12.84). An unrelated donor source and random urine protein to creatine ratio ≥2 mg/mg were significantly associated with no response to eculizumab (odds ratio 15, 95% CI 2.0-113.6 and OR 6.5, 95% CI 1.1-38.6 respectively). TA-TMA was independently associated with NRM despite early diagnosis and treatment with eculizumab in this large pediatric transplant cohort. Prognostic implications of D-dimer in TA-TMA 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-institutional clinical trials are needed to understand the impact of TA-TMA-targeted therapies.","journal":"American Journal of Hematology","year":2024,"id":431824,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1236492,"name":"Kaley French","orcid":null,"position":1,"is_corresponding":false},{"id":1087255,"name":"Anora Harris","orcid":null,"position":2,"is_corresponding":false},{"id":1100190,"name":"Elyse Bryson","orcid":null,"position":3,"is_corresponding":false},{"id":1100191,"name":"Laura Deeb","orcid":null,"position":4,"is_corresponding":false},{"id":1236493,"name":"Zuri Hudson","orcid":null,"position":5,"is_corresponding":false},{"id":1087257,"name":"Jeremy Obordo","orcid":null,"position":6,"is_corresponding":false},{"id":263442,"name":"Shanmuganathan Chandrakasan","orcid":"0000-0001-8007-9932","position":7,"is_corresponding":false},{"id":263444,"name":"Suhag Parikh","orcid":"0000-0002-6066-9852","position":8,"is_corresponding":false},{"id":674171,"name":"Benjamin Watkins","orcid":"0000-0002-6675-8071","position":9,"is_corresponding":false},{"id":569007,"name":"Elizabeth Stenger","orcid":"0000-0002-1386-6685","position":10,"is_corresponding":false},{"id":313728,"name":"Muna Qayed","orcid":"0000-0001-7689-343X","position":11,"is_corresponding":false},{"id":402916,"name":"Satheesh Chonat","orcid":"0000-0002-5909-0800","position":12,"is_corresponding":false},{"id":928672,"name":"Adrianna Westbrook","orcid":"0000-0001-9309-6205","position":13,"is_corresponding":false},{"id":305854,"name":"Jeffrey M. 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