Incidence and Outcomes of Patients with Thrombotic Microangiopathy after Transplant: Results of Prospective Screening through a Multi-Institutional Collaborative

Abstract

<h3>Background</h3> Thrombotic microangiopathy (TMA) is a severe complication of hematopoietic stem cell transplant (HSCT). <h3>Objective</h3> To determine incidence, risk factors and outcomes for patients who develop TMA following HSCT. <h3>Methods</h3> All patients were prospectively screened for TMA at participating centers with daily CBC, renal panel, and blood pressure; twice weekly LDH; and weekly urine analysis, including urine protein to creatinine ratio, from the start of the preparative regimen through the first 30 days. All labs were transitioned to weekly from day +30 to +100. TMA was diagnosed if (1) pathologic evidence of TA-TMA (e.g., renal biopsy with evidence of TMA), <i>or</i> (2) if meeting laboratory/clinical markers diagnostic for TMA (Figure 1). Each site retrospectively reviewed the data from screened patients from their respective center, and these data were aggregated to determine outcomes. <h3>Results</h3> 589 consecutive patients received TMA screening at the 12 participating centers from May 1, 2016 through June 30, 2018. TMA was diagnosed in 10% (20 of 198) of autologous and 21% (85 of 391) of allogeneic HSCT recipients. Patients undergoing HSCT for an underlying immune deficiency or bone marrow failure syndrome had a significantly higher rate of TMA (p=<0.001) (Figure 2). TMA was diagnosed at a median of 32 (IQR 24-44) days post-HSCT. Patients with TMA had a higher need for intensive care admission (46% vs. 17%, p=0.0001); increased incidence of respiratory failure (19% vs. 7%, p=0.0001); and increased incidence of bloodstream infections (44% vs. 22%, p=0.0001) in the first 100 days versus patients not diagnosed with TMA. Patients with TMA averaged significantly more days inpatient during the first 100 days than those without TMA (65 +/-27 vs. 41 +/-22 days; p=0.001). Further, patients with TMA averaged significantly more days in the ICU during the first 100 days than those without TMA (10 +/-20 vs. 3 +/-11 days; p=0.001). Six-month non-relapse mortality was significantly higher in the TMA group (19/105,18% vs. 19/484,4%; p=0.0001). Finally, six-month overall survival was significantly decreased in patients with TMA (84/105, 80% vs. 453/484,94%; p=0.0001) (Figure 3). In patients diagnosed with TA-TMA, 49 (47%) were treated with eculizumab and 3 (3%) received plasmapheresis. <h3>Discussion</h3> In this multi-center cohort we demonstrate a high incidence of TMA after pediatric HSCT through prospective screening. Patients with TA-TMA have higher morbidity and mortality when compared to patients without TA-TMA.