Sinusoidal obstructive syndrome, also known as hepatic veno-occlusive disease, is a potentially life-threatening complication that occurs in children undergoing haemopoietic stem-cell transplantation (HSCT). Differences in the incidence of genetic predisposition and clinical presentation of sinusoidal obstructive syndrome between children and adults have rendered the historical Baltimore and Seattle diagnostic criteria insufficient for children. In 2017, the European Society for Blood and Marrow Transplantation (EBMT) proposed the first paediatric diagnostic and severity grading guidelines for sinusoidal obstructive syndrome, intended for implementation across European centres. However, universally accepted paediatric criteria are needed to ensure prompt diagnosis, definitive treatment, and improved outcomes for children, adolescents, and young adults with sinusoidal obstructive syndrome, and to facilitate international clinical research collaboration. We convened an international panel of multidisciplinary experts including physicians with expertise in HSCT, paediatric intensive care, nephrology, hepatology, radiology, pathology, and transfusion medicine; HSCT advanced-practice providers and medical trainees; pharmacists; and translational and basic science researchers from the Pediatric Acute Lung Injury and Sepsis Investigators Network, the EBMT, the Pediatric Blood and Marrow Transplant Consortia, and several other institutions with extensive experience in sinusoidal obstructive syndrome. Panellists convened at The University of Texas, MD Anderson Cancer Center (Houston, TX, USA) in February, 2019, to evaluate the available evidence. In this expert position statement paper, we provide consensus recommendations for the international implementation of guidelines for the diagnosis, severity grading, and treatment of sinusoidal obstructive syndrome among children, adolescents, and young adults. We endorse universal adoption of paediatric diagnostic guidelines for sinusoidal obstruction syndrome as proposed by the EBMT, and provide implementation guidance for standardisation across centres; we have further proposed adjunctive use of age-appropriate organ-specific toxicity criteria for severity grading and provided prophylaxis and treatment considerations among children and adolescent and young adult patients. Key recommendations include: (1) liver biopsy, portal venous wedge pressure, and reversal of portal venous flow on Doppler ultrasonography should not be used for the routine diagnosis of sinusoidal obstructive syndrome in children, adolescents, and young adults; (2) platelet refractoriness can be defined as a corrected count increment of less than 5000–7500 following at least two sequential ABO-compatible fresh platelet transfusions; (3) hepatomegaly is best defined as an absolute increase of at least 1 cm in liver length at the midclavicular line; and if a baseline measurement is not available, hepatomegaly can be defined as greater than 2 SDs above normal for age; and (4) the presence and volume of ascites can be categorised as mild (minimal fluid by liver, spleen, or pelvis), moderate (<1 cm fluid), or severe (fluid in all three regions with >1 cm fluid in at least two regions).
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Paediatric patients are disproportionately affected by sinusoidal obstructive syndrome. Sinusoidal obstructive syndrome can progress to multi-organ dysfunction syndrome and require interdisciplinary care from supporting specialties. After careful consideration of existing and possible alternative criteria for diagnosis and grading of sinusoidal obstructive syndrome in paediatric patients, our international multidisciplinary expert panel proposes modifications to the EBMT paediatric criteria, formulating the first international multidisciplinary recommendations for diagnosis and severity grading of sinusoidal obstructive syndrome among children, adolescents, and young adults. We also provide guidance for more universal adoption and implementation of these criteria. Harmonised implementation of these paediatric-specific criteria should promote international collaboration in the field of sinusoidal obstructive syndrome research and improve patient outcomes. Contributors All authors made substantial contributions to this manuscript. All authors helped with the literature search and editing of the manuscript. KMM, RB, HAA, and SC wrote the manuscript. The manuscript was reviewed and approved by the Scientific Review Committee of the Pediatric Acute Lung Injury and Sepsis Investigators Network. Declaration of interests KMM has received two unrestricted medical education conference grants from Jazz Pharmaceuticals and MD Anderson Cancer Center. HA-A has a patent with applications in the field of gene modified T-cell therapy for cancer. SCh has a research grant and honoraria from Jazz Pharmaceuticals. SCo serves as consultant for Jazz Pharmaceuticals. FPT has received speaker honorarium and travel and meeting grants from Jazz Pharmaceuticals. NZ has financial interests in Boston Scientific, ENDO International PLC, Octapharma, and Stago Diagnostics, and is on the board of directors of North American Specialized Coagulation Laboratory Association. All other authors declare no competing interests. Acknowledgments We acknowledge Ms Brandy Adams, Ms Altrivice Revis, and Mr Tony Choy-Morga for administrative support at MD Anderson Cancer Center (Houston, TX, USA). We thank the Association for Pediatric Hematology Oncology Nursing for assistance with conference management and education related to sinusoidal obstructive syndrome. The meeting in Houston was sponsored via unrestricted medical education conference grants from The Children's Cancer Hospital at The University of Texas MD Anderson Cancer Center and Jazz Pharmaceuticals. Jazz Pharmaceuticals had no influence over panel member selection or content and was not present during deliberations and did not review this manuscript before publication.
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