Incidence and Outcomes of Patients with Thrombotic Microangiopathy after Transplant: Results of Prospective Screening through a Multi-Institutional Collaborative
Year: 2020
Type: article
Study design: Observational Study
Abstract: Background Thrombotic microangiopathy (TMA) is a severe complication of hematopoietic stem cell transplant (HSCT). Objective To determine incidence, risk factors and outcomes for patients who develop TMA following HSCT. Methods 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), or (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. Results 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. Discussion 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.
Authors: Christopher E Dandoy, Seth R. Rotz, Priscila Badia Alonso, Adam Lane, Christine Higham, Christopher C. Dvorak, Christine N. Duncan, Michelle Long Schoettler, Leslie E. Lehmann, Maria Cancio, James Killinger, Blachy Davila, Rachel Phelan, Swathi Prasad, Kris Michael Mahadeo, Sajad J Khazal, Nahal R Lalefar, Madhav Vissa, Anna Klunk, Deepika Bhatla, Nicholas J. Gloude, Eric Jon Anderson, Jeffrey S. Huo, Philip A. Roehrs, Jeffery J. Auletta, Stella M. Davies, Ranjit Chima, Sonata Jodele
Institutions: Cincinnati Children's Hospital Medical Center, Cleveland Clinic, Phoenix Children's Hospital, UCSF Benioff Children's Hospital, University of California, San Francisco, Dana-Farber Cancer Institute, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard University, Dana-Farber/Harvard Cancer Center, Memorial Sloan Kettering Cancer Center, Children's National, University of Minnesota, Medical College of Wisconsin, The University of Texas MD Anderson Cancer Center, Stanford University, Cardinal Glennon Children’s Medical Center, University of California San Diego, Rady Children's Hospital-San Diego, Levine Children's Hospital, Nationwide Children's Hospital
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W3003051754