Endotheliopathy Syndromes, TA-TMA and SOS, are Risk Factors for Morbidity and Mortality in Critically Ill Pediatric Hematopoietic Cell Transplant Recipients

Shivani Goel¹Erin Frost²Keiko Tarquino²Pradip P Kamat¹Taylor Fitch²Elizabeth Stenger²Katie Liu³Muna Qayed²Zhulin He³Adrianna Westbrook³Kirsten M Williams²Michelle L Schoettler^2*

• ¹Children's Healthcare of Atlanta Arthur M Blank Hospital, Atlanta, United States
• ²Children's Healthcare of Atlanta Inc Aflac Cancer and Blood Disorders Center, Atlanta, United States
• ³Children's Healthcare of Atlanta, Pediatric Biostatistics, Atlanta, GA, United States

Pediatric hematopoietic cell transplant (HCT) recipients who require intensive care unit (PICU) admission historically have high mortality rates. The HCT landscape is rapidly changing with the incorporation of novel graft versus host disease (GVHD),infection prevention strategies, and diagnosis and treatment of endothelial disorders—all potentially impacting risk factors for morbidity and outcomes of critically ill pediatric HCT recipients. This IRB approved single center, retrospective cohort, included all allogeneic recipients from 2019 to 2023 who required ICU admission in the first-year post HCT. Ninety-one unique PICU admissions in 56 HCT patients were identified. The median age at HCT was 8.4 years,30 (54%) were female. Thirty-four (61%) developed an early endotheliopathy syndrome, 27 (48.2%) TA-TMA (all treated with eculizumab), 21 (37.5%) SOS (all treated with defibrotide) and 14 (25%) both TA-TMA and SOS. Forty admissions (44%) required IMV. Risk factors (RF) for IMV included younger age, TA-TMA, SOS, RRT, and PICU length of stay ≥14 days. Of those requiring IMV, 15 patients (37.5%) failed extubation; no HCT or clinical features predicted extubation failure. Twenty-three admissions (25.3%) required renal replacement therapy (RRT). RF for RRT included TA-TMA, SOS, PICU LOS, and weight gain of ≥5% from dry weight at time of PICU admission. The duration that weight exceed 10% of dry weight before RRT was associated with inability to come off RRT. The 100-day PICU related mortality was 25% (95% CI 14, 37), though 1-year NRM from first ICU admission was 41% (95% CI 31, 51). RF for non-relapsed related mortality (NRM) included TA-TMA, and requiring RRT. Grade 3-4 acute GVHD was not a risk factor for ICU morbidity nor mortality. Infection was also not a risk factor, but the very high proportion of infection in the cohort limits the analysis. In this contemporary cohort with a high prevalence of infection, NRM of critically ill allogeneic HCT recipients was lower than historic rates and 62.5% of children requiring IMV were successfully extubated. SOS and TA-TMA, were risk factors for highly morbid ICU complications and death despite early intervention. Alternative approaches to these diseases and their drivers and initiation of early RRT may avert death.