Diagnosis and Treatment of VOD/SOS After Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS) is a rare complication characterized by hepatomegaly, right-upper quadrant pain, jaundice, and ascites, occurring after high-dose chemotherapy, hematopoietic stem cell transplantation (HSCT) and, less commonly, other conditions. We review pathogenesis, clinical appearance and diagnostic criteria, risk factors, prophylaxis, and treatment of the VOD occurring post-HSCT. The injury of the sinusoidal endothelial cells with loss of wall integrity and sinusoidal obstruction is the basis of development of postsinusoidal portal hypertension responsible for clinical syndrome. Risk factors associated with the onset of VOD and diagnostic tools have been recently updated both in the pediatric and adult settings and here are reported. Treatment includes supportive care, intensive management, and specific drug therapy with defibrotide. Because of its severity, particularly in VOD with associated multiorgan disease, prophylaxis approaches are under investigation. During the last years, decreased mortality associated to VOD/SOS has been reported being it attributable to a better intensive and multidisciplinary approach.

Clinical utilization of blinatumomab and inotuzumab immunotherapy in children with relapsed or refractory B‐acute lymphoblastic leukemia

“…32 SOS occurrence can be delayed and has been reported up to two years after HSCT, most frequently following dual-alkylator conditioning regimens. 31,33,34 24,36 The conversion to MRD negativity by FC in patients with primary refractory B-ALL in 11 of 12 patients using primarily blinatumomab is a particularly promising finding in our series. We further show that blinatumomab can convert patients from FC MRD positivity to HTS-MRD negativity, which may be associated with improved outcomes.…”

“…The precise mechanism for inotuzumab‐associated SOS remains unknown, but is thought likely due to its conjugation with calicheamicin that has been linked to SOS in patients with AML treated with gemtuzumab 32 . SOS occurrence can be delayed and has been reported up to two years after HSCT, most frequently following dual‐alkylator conditioning regimens 31,33,34 . Current strategies to prevent SOS include limiting the number of inotuzumab cycles, avoiding concomitant hepatotoxic medications and dual‐alkylator HSCT conditioning, and prophylactic use of ursodiol and/or defibrotide 35 .…”

Medical progress: Stem cells as a new therapeutic strategy for COVID-19

“…Subsequently, the second patient had a temperature rise to 38 °C which also resolved spontaneously within 24 h ( Irmak et al, 2020 ). Veno-occlusive disease (VOD), also referred to in the literature as sinusoidal obstruction syndrome (SOS), is a complication after stem cell transplantation ( Bonifazi et al, 2020 ). In VOD/SOS, metabolic products from the liver are not removed properly.…”

Veno-occlusive liver disease after hematopoietic stem cell transplantation and high-dose chemotherapy regimens. Literature review

“…Эффективность и безопасность ДФ при лечении ССО/ВОБ широко исследовались многими институтами [27]. Первое крупное мультицентровое исследование III фазы проводилось с 1995 по 2005 г. в 35 центрах США, Израиля и Канады.…”

“…ДФ пациентам вводили внутривенно в дозе 25 мг/кг/сут за 4 введения, длительность инфузии препарата составляла 2 ч. Средняя продолжительность терапии составила 21,5 дня, 10,7 % больных прекратили прием препарата из-за связанных с лечением побочных эффектов. Результаты исследования продемонстрировали лучшие показатели 100-дневной выживаемости и полного ответа у группы с ДФ (38,2 % против 25,0 % и 25,5 % против 12,5 % соответственно) [27,28]. В 2016 г. группой ученых из Швейцарии были опубликованы результаты ретроспективного (в период с 1999 по 2009 г.)…”