Hepatic sinusoidal obstruction syndrome post-chemotherapy in pediatric and adolescent age: case series of six patients in Qatar

Abstract

Dear Editor, The hepatic sinusoidal obstruction syndrome (HSOS) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT) and conventional radioand chemotherapy treatments for a variety of tumors. The diagnosis of HSOS has been historically built on Baltimore [1] and Modified Seattle [2] criteria, both for adults and children. In 2018, the European Society for Blood and Marrow Transplantation (EBMT) defined specific and more appropriate criteria for HSOS after HSCT in the pediatric population [3], based on the discrepancies of incidence, genetic predisposition, and clinical presentation observed between children and adults [2, 4]. The current study reports on 6 patients who developed HSOS after chemotherapy/radiotherapy as part of standardized protocols for disorders, outside the HSCT context, and were diagnosed with the new EBMT diagnostic criteria at Sidra Medicine from 2018 to 2020. Table 1 provides a summary about patients’ characteristics, course of disease, and outcome. All patients received supportive treatment and ursodeoxycholic acid therapy; 3 out of 6 received in addition defibrotide. All six patients showed hypoalbuminemia and needed albumin transfusions and diuretics. Two of the patients had ataxia telangiectasia (AT), autosomal recessive disease characterized by genomic instability predisposing to malignancies such as leukemia and lymphoma. The median duration of the HSOS episodes was 9 days. Five out of 6 HSOS episodes were resolved; one AT patient died due to multiorgan failure syndrome. Our study highlights the potential effect of the genetic background and predisposition to the development of HSOS as additional factor to be taken into consideration. The high incidence of HSOS subsequent to chemotherapy alone in our center can be linked to improved awareness and use of more appropriate diagnostic tools, but also may be to the effect of a germline predisposition, likely more frequent in the Arab and Qatari population. Only few genetic factors, GSTM1-null genotype and MTHFR 677CC/1298CC haplotype, have been described so far in the context of post-HSCT HSOS, after conditioning regimen with busulphan [5]. We believe that genetic predisposition should be specifically addressed and evaluated, especially in ethnicities and/or populations with high degree of inbreeding. In the literature, there are few reports of liver disease and even spontaneous HSOS in patients with AT [2]. It has been shown that asymptomatic AT patients can develop periportal fibrosis and even cirrhosis [6], suggesting that they are more prone to develop hepatic toxicity. Our report of HSOS during chemotherapy treatment in two siblings with AT calls for additional precautions to reduce the intensity of chemotherapy and use HSOS prophylaxis in similar cases. The application of the EBMT criteria gave an advantage in terms of proper recognition (one out of 6 patients would have not been reported using the old criteria) and thus timely treatment, as it is very well known that early intervention is highly important for better outcomes. In our opinion, also, albumin could be considered as additional diagnostic criterion in the future. More studies on HSOS caused by chemotherapy alone are needed for identifying treatment-risk categories, underlying Catherine Cole and Chiara Cugno contributed equally to this work.