Refractory Thrombocytopenia is the Earliest Diagnostic Criterion for Sinusoidal Obstruction Syndrome in Children

Abstract

Sinusoidal obstruction syndrome (SOS) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT), whose diagnostic criteria changed over time to achieve a timelier diagnosis. Recently, pediatric-specific criteria presented by the European Society for Blood and Marrow Transplantation (pEBMT) incorporated transfusion-refractory thrombocytopenia (RT) as an early indicator of SOS in children. However, a comparison of all individual diagnostic parameters belonging to pEBMT and former SOS diagnostic criteria has never been performed. This retrospective study conducted at a pediatric tertiary care hospital analyzed all pediatric HSCT cases diagnosed with SOS among 170 children transplanted from 2009 to 2023. Eleven patients developed SOS during this period (incidence: 11/170, 6.5%). pEBMT, Seattle, and Baltimore criteria were retrospectively applied to the 11 cases and compared, showing that RT was the earliest fulfilled parameter (median onset: 6 d post-HSCT). pEBMT and Seattle criteria identified 11/11 SOS cases, with pEBMT leading to an earlier diagnosis. RT typically manifested before diagnosis, with significantly higher platelet transfusion requirements before diagnosis than after. RT is the earliest satisfied criterion in pediatric SOS and typically occurs in the initial stages of the disease before diagnosis. Further research is needed to identify additional early indicators of pediatric SOS.

FIGURE 1

Retrospective assessment of SOS diagnostic criteria in included patients. A, Venn diagram showing the number of patients diagnosed through a retrospective application of each diagnostic criteria. B, Scatter plot showing the time required for each criterion to be satisfied in included patients. C, Violin plot showing the time required for each specific parameter of the 3 assessed criteria to be satisfied. Refractory thrombocytopenia (RT) was satisfied significantly earlier than any other parameter. BAL/Baltimore indicates Baltimore criteria; pEBMT, pediatric European Society for Blood and Marrow Transplantation criteria; SEA/Seattle, modified Seattle criteria. ***P<0.001.

FIGURE 2

Order of appearance of the 5 parameters belonging to pEBMT criteria in included patients. pEBMT indicates pediatric European Society for Blood and Marrow Transplantation criteria; RT, refractory thrombocytopenia.

FIGURE 3

Refractoriness to platelet transfusions before and after diagnosis of SOS in included patients. A, Percentage of days in which the patient required platelet (PLT) transfusions before and after diagnosis of SOS. B, Platelet transfusion requirement (PTR) before and after diagnosis of SOS. C, Heat map showing the days when platelets were transfused (colored squares), and the amount (mL/kg) of platelet transfused for each included patient. Gray squares indicate days where platelets were not transfused. The yellow cross indicates the day when the diagnosis of SOS was established in clinical practice. The heat map shows that the days where platelets were transfused are highly distributed in the prediagnosis period.