Sinusoidal Obstructive Syndrome Among Pediatric and Adolescent and Young Adult Patients: Analysis of Pediatric EBMT Diagnostic and Severity Criteria at MD Anderson

Background: Sinusoidal obstructive syndrome (SOS) is a potentially catastrophic complication of stem cell transplantation (SCT) which disproportionately affects younger patients. The incidence of SOS may vary widely depending on the diagnostic criteria (Baltimore versus Seattle), and delays in initiation of definitive treatment remains the most important predictor of outcome. Recently proposed pediatric diagnostic and severity grading criteria by the European Society of Blood and Marrow Transplantation (EBMT) may offer increased sensitivity and allow for more prompt diagnosis, but the extent to which these have been adopted and/or validated by centers in the United States is unclear. Methods: This is a retrospective analysis of all patients undergoing SCT on the Pediatric service at MD Anderson Cancer Center from 2009-2019. Patient records were reviewed for diagnosis of SOS. Among patients identified with SOS, application of Baltimore, Seattle and pediatric EBMT (pEBMT) criteria were compared. Descriptive statistics were used for data analysis where appropriate. Results: A total of 248 patients received 268 transplants during the study period. Patient characteristics are summarized in Table 1. When Baltimore criteria was used the incidence of SOS was 4.5% (n=12) as compared to 8.2% (n=22) when the Seattle or pEBMT criteria were applied. At diagnosis, the majority of these patients had moderate to very severe disease according to pEBMT criteria. The median time to diagnosis of SOS varied according to diagnostic criteria used, with a trend to earlier diagnosis with pEBMT criteria (13 days post-SCT with pEBMT versus 15 days with Seattle/Baltimore) as shown in Table II. Prior exposure to inotuzumab and gemtuzumab were associated with high rates of SOS (75% and 86% respectively). Anicteric SOS, refractory thrombocytopenia and rising bilirubin from a baseline value on 3 consecutive days or bilirubin ≥2 mg/dL within 72 hours were present in 63.6%, 77.3% and 91% of patients with SOS, when pEBMT criteria were applied. Late-onset SOS (diagnosed after 21 days post-SCT) was present in 22.7% of patients when Seattle or pEBMT criteria were applied (n=5) and could not be diagnosed per Baltimore criteria. Severe SOS was eventually observed in 95% of patients. Severe ascites requiring paracentesis (23%), impaired coagulation (77%), respiratory distress requiring supplemental oxygen and/or invasive pulmonary ventilation ( 55%), delirium (32%), acute kidney injury/KDIGO Stage 3/requiring renal replacement therapy (50%) were observed. Defibrotide treatment was initiated in 55% of patients with a median duration of treatment of 26 (3-74) days and complete resolution of SOS was observed in 42% of these patients. For patients who were initiated on defibrotide on the day of diagnosis (n=7) versus those who were not (range 1-11 days) the median time to complete resolution of SOS was 35 and 20 days respectively (p=0.2). Conclusions: To our knowledge, this is the first reported retrospective analysis of SOS among pediatric and adolescent young adult SCT patients in the United States using pEBMT SOS diagnostic and severity criteria. Our study was limited by small sample size associated with single center analyses. Use of the pEBMT criteria showed a trend to earlier time to diagnosis by a median of two days. This is a potentially clinically significant finding, as a delay in initiation of defibrotide among children with severe SOS, has been associated with statistically significant decreased rates of complete resolution. Inherent flaws of the Baltimore and Seattle criteria are the time restriction and reliance of hyperbilirubinemia for the diagnosis in children and adolescents and young adults. Our retrospective analysis suggests that pEBMT criteria for the diagnosis of SOS among children and young adults may be appropriate, especially given the rates of anicteric and late-onset SOS seen in this population. Download : Download high-res image (248KB) Download : Download full-size image Disclosures Petropoulos: Foundation for the Accreditation of Cellular Therapy (FACT): Membership on an entity's Board of Directors or advisory committees, Other: Foundation for the Accreditation of Cellular Therapy (FACT). Kebriaei: Amgen: Research Funding; Jazz: Consultancy; Pfizer: Honoraria; Kite: Honoraria. Wierda: Xencor: Research Funding; Janssen: Research Funding; Loxo Oncology Inc.: Research Funding; KITE pharma: Research Funding; Juno Therapeutics: Research Funding; Gilead Sciences: Research Funding; Acerta Pharma Inc: Research Funding; Pharmacyclics LLC: Research Funding; Genentech: Research Funding; GSK/Novartis: Research Funding; AbbVie: Research Funding; Cyclcel: Research Funding; Oncternal Therapeutics Inc.: Research Funding; Miragen: Research Funding; Sunesis: Research Funding. Mahadeo: Recipient of unrestricted medical education grant from Jazz: Research Funding; PI for ATARA EBV CTL Trials: Other: Other .