Real-World Analysis of the Underdiagnosis, Clinical Outcomes and Associated Burden of Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy (HSCT-TMA) in the United States of America

Background Thrombotic microangiopathy (TMA) associated with hematopoietic stem cell transplantation (HSCT-TMA) is a serious post-transplant complication. HSCT-TMA is difficult to diagnose due to overlapping symptoms with other conditions and a lack of universally adopted diagnostic criteria. Objectives This study aimed to assess the incidence and diagnosis of HSCT-TMA in real-world US practice, including possible missed diagnoses, alongside clinical outcomes and any associated burden of HSCT-TMA. Methodology This retrospective, observational study investigated the incidence of HSCT-TMA from July 2009-August 2020 using data from the TriNetX US Electronic Medical Record (EMR) database. Patients who underwent autologous or allogeneic HSCT and had conditioning regimens recorded were stratified into three cohorts: confirmed, suspected, and non-TMA (Image 1). Baseline demographics and clinical characteristics, clinical outcomes, and all-cause unadjusted healthcare resource utilization within 12 months of HSCT, were assessed. Statistical comparisons were made using the non-TMA cohort (p<0.05). Results In total, 16,809 adult and 901 pediatric patients had an HSCT procedure code and recorded conditioning regimen (Image 1). Baseline demographics were similar across all groups (Image 2). Mortality within the first year of HSCT was significantly higher in adults with confirmed (40.0%) and suspected (30.7%) TMA compared to adults without TMA (13.6%). Mortality was numerically highest in pediatrics with confirmed TMA (26.7%) followed by suspected TMA (23.4%), and lowest in pediatrics without TMA (15.8%). Comorbidity impact was highest in confirmed TMA patients, and HSCT complications were more common in both confirmed and suspected TMA patients. Clinical outcomes in the first year after HSCT were significantly worse in confirmed and suspected TMA patients than in non-TMA patients (Image 2). Patients with confirmed and suspected TMA had a significantly higher frequency of oxygen/intubation compared with non-TMA patients. Dialysis rates were significantly higher in patients with confirmed TMA (adults, 26.4%; pediatrics, 20.0%) compared to patients without TMA. Patients with confirmed and suspected TMA had significantly greater use of targeted therapies and a higher number of total ICU visits, compared with non-TMA patients (Image 2). Conclusions This study showed that HSCT-TMA has a high mortality and morbidity burden. Furthermore, it highlighted that HSCT-TMA is underdiagnosed in the real-world, as more patients met published diagnosis criteria (suspected TMA) than had recorded diagnosis codes. Patients with suspected TMA also had worse outcomes and higher disease burden than patients without TMA. This study highlights the need for timely diagnosis of this severe complication, as well as novel approaches to treat and manage this vulnerable population.