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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.

SUBMITTER: Bonifazi F

PROVIDER: S-EPMC7147118 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Bonifazi Francesca F Barbato Francesco F Ravaioli Federico F Sessa Mariarosaria M Defrancesco Irene I Arpinati Mario M Cavo Michele M Colecchia Antonio A

Frontiers in immunology 20200403

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 ...[more]

PMID: 32318059

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Project description:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapeutic option for many patients with hematological malignancies and nonmalignant hematopoietic disorders. To achieve stable engraftment of donor hematopoietic stem cells (HSCs), recipient HSC deletion is needed to create space for incoming donor HSCs and donor HSCs must escape immune rejection by the recipient. Conventional allo-HSCT requires high dose of irradiation and/or chemotherapy to produce sufficient host stem cell and immune system ablation to permit donor HSC engraftment. However, these procedures also result in nonspecific tissue injury that can cause short- and long-term adverse effects as well as incite and amplify graft-versus-host-disease (GVHD). The delivery of targeted radiotherapy to hematopoietic tissues with the use of a radioimmunoconjugate (ROIC) as a part of transplant preparative regimen has shown clinical benefits. ROIC clinical data provide evidence for decreased relapse without increased transplant-related mortality by delivering higher targeted radiation to sites of malignancy than when given in a nontargeted fashion. An alternative approach to allo-HSCT has been developed and tested in preclinical mouse models in which nonmyeloablative preconditioning with low dose of the alkylating agent (busulfan) or lower systemic dose of irradiation combined with co-stimulatory pathway blockade (CTLA4-Ig, anti-CD40L monoclonal antibody) and/or immunosuppressive drugs have been used. Under these conditions, mixed chimerism and transplantation tolerance to fully MHC mismatched donor marrow was observed. Recently, several novel proof-of-concept antibody-mediated preconditioning methods have been developed that can selectively target hematopoietic stem and immune cells with minimal overall toxicity. Antibody-drug-conjugate (ADC) combined with reduced intensity conditioning or high dose ADC as single dose monotherapy have shown promise for allo-HSCT in preclinical models. The purpose of the current review is to discuss the literature exploring antibody-based conditioning that includes native antibody, radiolabeled antibody conjugates, and ADC for allo-HSCT.

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

Publications

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

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