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Abstract

Transplant-associated thrombotic microangiopathy (TA-TMA) is a serious complication of hematopoietic stem cell transplant (HSCT). The introduction of eculizumab, a complement inhibitor, represented an advancement in the treatment of TA-TMA and impacted practice at Oregon Health and Science University (OHSU) since July 2015. In this study, we performed a retrospective review of pediatric allogeneic HSCTs occurring between August 2008 -September 2019 at OHSU to describe the incidence of TA-TMA over time and eculizumab utilization. We used a modified diagnostic criteria permitting retrospective disease evaluation across disparate periods. The four criteria defining TA-TMA were adapted from the Bone Marrow Transplant Clinical Trials Network 2005 and City of Hope Criteria 2013: 1) Anemia with schistocytes, 2) LDH > 2x the upper limit of normal, 3) Serum creatinine > 1.5x baseline, 4) Negative indirect coombs OR platelets <50 x 109/ml. We found that 17 of 142 patients undergoing HSCT met all four criteria (incidence 12.0%). Of those, 6 out of 85 patients (7%) were identified between 2008 to 2015 (pre-eculizumab era) while 11 out of 57 patients (19%) were identified between 2015 to 2019 (post-eculizumab era). Patients with TA-TMA were more likely to be admitted to the pediatric intensive care unit in the post-eculizumab era (82% vs 24%, P=0.006). TA-TMA had no significant impact on diagnosis of GVHD. Our single center experience demonstrated an increased incidence of TA-TMA since the introduction of eculizumab in 2015 at OHSU. This increase coincides with an increase in TA-TMA in non-malignant transplants.

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