MD Anderson-convened consortium provides first universal recommendations for pediatric patients with sinusoidal obstructive syndrome

Universally accepted pediatric criteria are needed to ensure prompt diagnosis, treatment and improved outcomes for patients

The University of Texas MD Anderson Cancer Center convened an international panel of multidisciplinary experts earlier this year to evaluate the current standards and to create the first international guidelines for the diagnosis, severity grading and treatment of sinusoidal obstructive syndrome, a potentially life-threatening complication among children, adolescents and young adults. The recommendations were published in the Dec. 6 issue of The Lancet Haematology.

The recommendations support universal adoption of pediatric diagnostic guidelines for sinusoidal obstruction syndrome – also known as hepatic veno-occlusive disease – proposed by the European Society for Blood and Marrow Transplantation (EBMT), and provide direction for implementing standardized practices. The recommendations also propose supplemental use of age-appropriate organ-specific toxicity criteria for severity grading and provide prophylaxis and treatment considerations among pediatric patients.

“Sinusoidal obstructive syndrome is a potentially fatal complication that can lead to multi-organ dysfunction syndrome and require interdisciplinary care,” said Kris Mahadeo, M.D., associate professor of Pediatrics and chief of Stem Cell Transplant and Cellular Therapy at MD Anderson. “It is imperative to adopt and implement standardized practices for the treatment and diagnosis of this disease so we can greatly improve patient outcomes around the world.”

In February 2019, Mahadeo and a panel of international experts studied the available guidelines for diagnosis and treatment of sinusoidal obstructive syndrome and evaluated barriers to global implementation. Historically, the Baltimore and modified Seattle criteria have been used for the diagnosis of sinusoidal obstructive syndrome; however, the incidence, course and severity among adolescents are highly variable and can be difficult to predict.

In 2017, the EBMT proposed the first pediatric diagnostic and severity grading guidelines for sinusoidal obstructive syndrome, addressing the discrepancy between children and adults in terms of incidence, genetic predisposition and presentation of the disease. A need remained for universally accepted pediatric criteria among transplant physicians and other sub-specialty physicians who treat more advanced stages that include multi-organ dysfunction. After consideration of existing possible alternative criteria for diagnosis and grading, the panel proposed modifications to the EBMT and created the first international multidisciplinary recommendations.

Key recommendations include:

  • Endorsement of universal adoption of Pediatric Diagnostic Criteria for sinusoidal obstructive syndrome
  • Implementation guidance for standardization across centers, including accepted definitions of key diagnostic criteria, such as platelet refractoriness, hepatomegaly and ascites
  • Recognition that platelet refractoriness is an early indicator of sinusoidal obstructive syndrome and can be defined as a corrected count increment of less than 5,000-7,500 following at least two sequential ABO-compatible fresh platelet transfusions
  • Incorporation of accepted pediatric specific organ dysfunction severity criteria (KDIGO, CAPD) into the severity grading of sinusoidal obstructive syndrome

The paper notes that adoption of universal guidelines will allow global collaboration in the field and will promote future studies to better understand sinusoidal obstructive syndrome pathology, the many functions of the resting endothelium and, ultimately, improve patient outcomes.

MD Anderson team members who collaborated on the development of the recommendations included Keri Schadler, Ph.D., Priti Tewari, M.D., Sajad Khazal, M.D., Shulin Li, Ph.D., Avis Harden, M.D., and Francesco Paolo Tambaro, M.D., all of the Division of Pediatrics; Partow Kebriaei, M.D., of Stem Cell Transplantation and Cellular Therapy; Jun-ichi Abe, M.D., of Cardiology and Susan Abraham, M.D., of Pathology. Other authors included Rajinder Bajwa, M.D. and Jeffery J Auletta, M.D., of Nationwide Children’s Hospital; Hisham Abdel-Azim, M.D., of Keck School of Medicine of USC; Leslie E Lehmann, M.D. and Christine Duncan, M.D., of Boston Children’s Hospital/ Dana-Farber Cancer Institute; Nicole Zantek, M.D., Ph.D, of University of Minnesota; Jennifer Vittorio, M.D., of Columbia University Medical Center; Joseph Angelo, M.D., of Texas Children’s Hospital; Jennifer McArthur, D.O., of St. Jude Children’s Research Hospital;  Sherwin Chan, M.D., of Children's Mercy Kansas City; Sung Won Choi, M.D., of C.S. Mott Children’s Hospital; Basirat Shoberu, PharmD., of Children’s Hospital of Montefiore; Krzysztof Kalwak, M.D., Ph.D., of Wroclaw Medical University; Jerelyn Roberson Moffet, R.N., of Duke Children's Hospital & Health Center; Katharina Kleinschmidt, M.D., of University Hospital Regensburg; Paul G Richardson, M.D., of Dana Farber Cancer Institute; Selim Corbacioglu, M.D., of University Hospital Regensburg on behalf of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network and the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation

Kris Mahadeo, M.D.