UCLA

ABSTRACT OF THE DISSERTATION

Sinusoidal Obstruction Syndrome Among Pediatric Hematopoietic Stem Cell Transplant Patients

by

Tracy Ono Doctor of Philosophy in Nursing University of California, Los Angeles, 2024 Professor Dorothy J. Wiley, Chair

Evidence strongly supports hematopoietic stem cell transplants (HSCTs) for the treatment of malignancy. HSCT carries risks, including fatality, that are associated with intensive conditioning radiation and chemotherapy that optimize the bone marrow for stem-cell implantation. Hepatic sinusoidal obstruction syndrome (SOS) is a rare complication that disproportionately affects children where progression to severe SOS requires advanced life support and carries high mortality (>80%). A historical literature review and two quantitative studies explored nurse-sensitive predictors for SOS and the association between SOS and malignancy relapse. The literature review targeted people aged 19 and younger receiving HSCT treatment. Five themes emerged: diagnostic and severity grading; pharmacotherapy, primarily concentrated on defibrotide; biologic indicators; advances in diagnostic imaging; and clinical SOS treatment and management variability. We evaluated the associations between heart rate patterns and SOS using routine, clinically recorded electronically-measured heart rates for 0.5 to 19-year-olds following HSCT. While SOS-affected youth consistently showed increasing mean heart rates across 14 and 28 days following HSCT, unaffected minors showed flat patterns. For example, among 0.5 to 2.5-year-olds, mean heart rates increased 1.37-fold over the first 14 days, compared to no change observed among unaffected same-aged children. These and other acute changes in heart rate patterns surrounding HSCT may be new biomarkers for SOS. The associations between SOS and malignancy relapse following HSCT evaluated follow-up data for 180 pediatric HSCT recipients, 0.5 to 19 years of age. Twenty-eight diagnosed with SOS showed a shorter time to relapse in bivariate analysis. Multivariable adjusted models showed SOS was associated with a 3.2-fold higher odds of relapse than observed among youth without SOS. Alkylating chemotherapy was independently associated with lower odds of relapse in these analyses. These analyses underscore a critical need to evaluate routinely collected EMR data, especially data electronically evaluated (vs. counts by many personnel), as risk factors for disease outcomes that drive care and prescriptive interventions among people treated with HSCT. Evaluating nurse-sensitive indicators for early diagnosis of SOS and malignancy relapse prevention may improve patient care, survival, and quality of life.