Introduction
Sinusoidal obstruction syndrome (SOS)/veno-occlusive disease (VOD) is a serious complication after hematopoietic stem cell transplantation (HSCT). The diagnostic criteria of SOS/VOD were based on clinical findings, recently, ultrasonography (US) has been suggested as one of modalities to assess hepatomegaly and ascites to diagnose SOS/VOD in pediatric patients1. Considering the pathogenesis of SOS/VOD, that is endothelial damage in sinusoid leading to impairment of blood flow and congestion. If detecting alteration of blood flow by US is possible, US would be an effective tool. We previously reported the usefulness of original US scoring system, which includes assessing hepatomegaly, ascites, and blood flow alteration. It is called Hokkaido US-based scoring system (HokUS) -102/63 in diagnosing SOS/VOD. However, the usefulness of HokUS-10/6 for diagnosing SOS/VOD in pediatric patients remains unclear.
Aims & Methods
To elucidate diagnostic performance of HokUS-10/6 for SOS/VOD in pediatric patients.The patients who underwent HSCT from Jan. 2008 to Feb. 2023 in our institution were enrolled. HokUS-10/6 were applied to the patients before HSCT and on day 14, 28 or when the signs of SOS/VOD appeared after HSCT. SOS/VOD was clinically diagnosed by the modified Seattle4 or the Baltimore criteria5 or the European Society for Blood and Marrow Transplantation criteria in pediatric patients5. HokUS-10 consists of 10 parameters: 1) hepatomegaly in the left lobe and 2) right lobe, 3) dilatation of the main portal vein (PV), 4) hepatofugal flow in the main PV, 5) decreased velocity of the PV, 6) dilatation of the para-umbilical vein (PUV), 7) appearance of blood flow signal in the PUV, 8) gallbladder (GB) wall thickening, 9) ascites, and 10) increased resistive index of the hepatic artery (HA-RI). In HokUS-6, presence of ascites is mandatory. When ascites was detected, 6 parameters were evaluated: moderate amount of ascites, appearance of PUV blood flow signal, GB wall thickening, PV dilatation, PV velocity decrease, and HA-RI increase. The severity is divided into five categories: grade 1 = mild; grade 2 = moderate; grade 3 = severe; grade 4 = very severe; and grade 5 = death5. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy.
Results
In total 101 patients (male 65 and female 36), median age 6 (range 0 to 16), were analyzed, of whom 13 patients (12.9%) were diagnosed as SOS/VOD at a median of 28 days (range, 3-102 days) after HSCT. Three (20%) patients showed hyperbilirubinemia (> 2 mg/dl), while all patients had transfusion-refractory thrombocytopenia, hepatomegaly, and ascites. When cut-off value of HokUS-10 and 6 were set 4 and 2, highest AUC was calculated as 0.981 (95% CI : 0.958 - 1) and 0.966 (95% CI : 0.930 - 1), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for diagnosing SOS/VOD were, 100%, 85.2%, 50.0%, and 100% by HokUS-10, and 84.6%, 95.5%, 73.3%, and 99.7% by HokUS-6, respectively. Using cut off value set at 5 same as adults in HokUS-10, sensitivity declined to 84.6% (two patients showed false negativity). HokUS-10/6 detection of SOS/VOD preceded five days its clinical diagnosis in 1 case, clinical diagnosis was made following US detection on the same day in the other cases. The numbers of patients with SOS/VOD grade 1, 2, 3, 4 and 5 were 0, 0, 2, 11 and 0, respectively.
Conclusion
HokUS-10/6 scoring system showed good diagnostic performance in pediatric patients same as in adults. The cut off value of HokUS-10 would be better to use 4 rather than 5 in pediatric patients.
References
1. Mohty M, et al. Bone Marrow Transplant 2016; 51(7): 906-912.
2. Nishida M, et al. Biol Blood Marrow Transplant 2018; 24(9): 1896-1900.
3. Nishida M, et al. Int J Hematol 2021; 114(1): 94-101.
4. Jones RJ, et al. Transplantation 1987; 44(6): 778-783.
5. McDonald GB, et al. Ann Intern Med 1993; 118(4): 255-267.
Disclosure
Mutsumi Nishida has received a research grant and a speaker fee from Nippon Shinyaku, and a speaker fee from Pfizer. Takanori Teshima has received research grants and speaker fees from Chugai, Kyowa Kirin, Nippon Shinyaku, Sumitomo Pharma and Astellas, research grants from Fuji Pharma, Asahi Kasei Pharma, Eisai, Ono, Shionogi, Priothera SAS and Luca Science, speaker fees from AbbVie, Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme, Celgene and Janssen, and participation on a Data Safety Monitoring Board or Advisory Board at Novartis, Meiji Seika Pharma, Daiichi Sankyo, Asahi Kasei Pharma, Astellas, AstraZeneca, Takeda, Janssen, Roche Diagnostics, Sumitomo Pharma, Celgene and Sanofi. Rest of the authors declare that they have no conflict of interest.