Improved detection of sinusoidal obstructive syndrome using pediatric–AYA diagnostic criteria and severity grading

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Abstract

New diagnostic criteria and severity grading for sinusoidal obstructive syndrome (SOS) among pediatric and adolescent young adult (AYA) patients have been recently endorsed by international consensus. The extent to which these have been adopted in the US remains unclear. We sought to assess the potential impact via retrospective application of these criteria among patients treated at a large academic center in the United States. This is a single center retrospective study of pediatric–AYA patients who underwent hematopoietic cell transplantation (HCT) between July 2009 and 2019. The incidence of SOS was assessed using historic Baltimore and Seattle diagnostic criteria and compared with more recent guidelines (pEBMT) as proposed by the Paediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation. Among 226 patients, application of the pEBMT diagnostic criteria was associated with a higher incidence (15.9%) and earlier time to diagnosis of SOS (by 2.5–3 days) compared with the modified Seattle (12.3%), and Baltimore (6.6%) criteria, respectively. The pEBMT criteria were sensitive and highly specific. Refractory thrombocytopenia was present in 75% of patients at diagnosis. Approximately 61% of patients with SOS were anicteric at diagnosis, though the majority (94.4%) developed hyperbilirubinemia as SOS progressed over a median time of 4 (1–57) days. Application of pEBMT criteria may have resulted in earlier indication for definitive treatment by 3 days. Timely diagnosis and administration of definitive treatment of SOS has been associated with improved outcomes. Prospective studies may better characterize the risk factors and natural course of SOS using pEBMT criteria.

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Fig. 1: Identification of patients with sinusoidal obstructive syndrome.
Fig. 2: Patient outcome based on severity grade of SOS.
Fig. 3: 100-Day survival (Fig. 3a) and overall survival (Fig. 3b) of patients with and without SOS post-HCT.

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Acknowledgements

We thank our patients and their caregivers, the nursing unit staff for their clinical care, and Ms Latarsha Williams and Marisol Gonzalez for administrative support.

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KMM conceptualized the paper. DR, AP, MK, AH, and BS participated in data collection. JW and DR completed statistical analysis. DR, KMM, and FPT wrote the manuscript. KMM, PT, DP, PK, and SJK treated patients. All authors reviewed and/or edited the manuscript and made meaningful contributions before submission.

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Correspondence to D. Ragoonanan.

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PK has research support from Amgen and ZIOP harm; has served on advisory boards for Pfizer, Kite and Novartis and reports consulting fees from Jazz Pharmaceuticals FPT reports personal fees from Jazz Pharmaceuticals outside the submitted work.

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Ragoonanan, D., Khazal, S.J., Wang, J. et al. Improved detection of sinusoidal obstructive syndrome using pediatric–AYA diagnostic criteria and severity grading. Bone Marrow Transplant 56, 175–184 (2021). https://doi.org/10.1038/s41409-020-00998-w

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