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• W3211985135 abstract "Abstract Introduction Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), with mortality over 80%. Effective management of TA-TMA is hampered by obscure pathogenesis and delayed diagnosis. There are no well-acknowledged therapeutic strategies for TA-TMA. TA-TMA-directed therapy includes therapeutic plasma exchange (TPE), eculizumab, rituximab, and defibrotide. The efficacy and outcome of TPE for the treatment of TA-TMA remain controversial. To our knowledge, this is the largest cohort to date of patients treated with TPE for TA-TMA after allo-HSCT. We aimed to identify predictors of response and mortality in patients with TA-TMA who received TPE, and to recognize patients who will benefit from TPE management. Methods A total of 6241 subjects who underwent allo-HSCT were performed at Peking University People's Hospital from January 2010 to December 2019, of whom 538 patients were diagnosed with TA-TMA, with a cumulative incidence of 8.6%. Among them, 82 consecutive critically ill TA-TMA patients received TPE. TA-TMA was diagnosed using the criteria proposed by Cho et al. TPE was not performed in a protocol-defined manner. Patients were classified as achieving complete response (CR) if they showed disappearance of schistocytes, resolution of any changes in mental status, normalization of lactic dehydrogenase, and were not receiving red blood cells and platelet transfusions. Patients were considered to have achieved no response (NR) when they showed no improvement of laboratory features, remained dependent on red blood cell and/or platelet transfusions, or died with active TA-TMA. Subjects were considered to have a partial response (PR) when they did not meet the criteria for either CR or NR (BMT 2010; Blood 2020). Results TA-TMA was diagnosed at a median time of 64.5 [IQR 38.8-158] days post-HSCT. The 42 men (51.2%) and 40 women (48.8%) had an average age of 35.3 years. Renal involvement (59.8%), central nervous system dysfunction (70.7%), gastrointestinal (GI) bleeding (73.2%), and concomitant acute graft-versus-host disease (aGVHD, 78%) were common in our cohort of TA-TMA patients. All 82 patients in our analysis received TPE, and adjunctive TA-TMA-targeted therapy included the use of rituximab (11 patients), rituximab plus eculizumab (1 patient), and defibrotide (1 patient). However, the additional therapy showed no significant difference between the response and nonresponse groups. The median time from TA-TMA to TPE initiation was 8 days [IQR 2.0-16.5], and the cumulative volume of TPE was 6 L [IQR 3.6-8.5]. Our data revealed that the overall response was 52.4% (43/82), comprising 4 CRs and 39 PRs. Early TPE initiation trended towards a better response, but this difference was not statistically significant. The multivariate analysis showed that patients with GI bleeding (OR, 6.26; 95% CI, 1.30-30.12), grade III-IV aGVHD (OR, 5.00; 95% CI, 1.50-16.68), lower cumulative volume of TPE (OR, 8.51; 95% CI, 1.91-38.05), and severe anemia (OR, 7.48; 95% CI, 2.20-25.49) were less likely to respond to TPE. Regarding treatment outcome, 57% (47/82) of cases survived 100 days post HSCT, and 20% (16/82) survived 100 days after the diagnosis of TA-TMA. With a median follow-up of 467 days [IQR 248-1002], the OS at 1 year after TA-TMA was 15%. The leading causes of death were infection, active TA-TMA, and multiple organ dysfunction syndrome (MODS). The Kaplan-Meier analysis showed that GI bleeding, grade III-IV aGVHD, and no response to TPE were associated with poor survival at 1-year post TA-TMA (Figure 1). By multivariate analysis, TA-TMA patients treated with TPE had dismal survival with GI bleeding, lower loading volume of TPE, and elevated total bilirubin. Conclusions The results of this large cohort of real-world practice indicate that TPE may be effective for TA-TMA depending on given clinical circumstances. Our data underscore that GI bleeding is independently associated with poor response to TPE and mortality, while grade III-IV aGVHD is again confirmed as predicting a dismal response to TPE. We hypothesize that higher volume of TPE is warranted to achieve resolution and favorable outcome of TA-TMA. Multicenter prospective studies are required to further verify whether these patients could benefit from TPE and seek a paradigm for TPE in the management of TA-TMA. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare." @default.
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• W3211985135 date "2021-11-05" @default.
• W3211985135 modified "2023-10-16" @default.
• W3211985135 title "Treatment Outcome and Efficacy of Therapeutic Plasma Exchange for Transplant-Associated Thrombotic Microangiopathy in a Real-World Large Cohort Study" @default.
• W3211985135 doi "https://doi.org/10.1182/blood-2021-149373" @default.
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