Incidence, Predictors, and Outcomes of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation

Lewis, Clinton; Kim, Haesook T.; Roeker, Lindsey E.; Cutler, Corey; Koreth, John; Nikiforow, Sarah; Armand, Philippe; Gootpu, Mahasweta; Romee, Rizwan; Glotzbecker, Brett; Nageshwar, Prashant; Antin, Joseph H.; Alyea, Edwin P.; Richardson, Paul G.; Soiffer, Robert J.; Ho, Vincent T.

doi:10.1016/j.bbmt.2019.10.024

Cited by 20 publications

(13 citation statements)

References 31 publications

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“…The first question requires a thorough work-up of the endothelial toxicity of agents commonly used in the pre-SCT setting, such as fludarabine, alkylators, and anthracyclines, but also irradiation [91,92], but of course also of the contributions of vascular comorbidity unrelated to the neoplastic disease. Regarding the second question, a large variety of drugs frequently employed during or after SCT, such as CNI, sirolimus, calcium channel blockers, and angiotensin-II inhibitors can affect endothelial integrity and may demand patient-based endothelial monitoring [93][94][95][96]. Because of its easy accessibility, also for retrospective analyses, EASIX might be a particularly useful tool for this purpose.…”

Section: Adjusting Anti-neoplastic and Immunosuppressive Regimens To Endothelial Cell Functionmentioning

confidence: 99%

Endothelial cell dysfunction: a key determinant for the outcome of allogeneic stem cell transplantation

Luft

Dreger

Radujkovic

2021

Bone Marrow Transplant

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Allogeneic hematopoietic stem cell transplantation (alloSCT) carries the promise of cure for many malignant and non-malignant diseases of the lympho-hematopoietic system. Although outcome has improved considerably since the pioneering Seattle achievements more than 5 decades ago, non-relapse mortality (NRM) remains a major burden of alloSCT. There is increasing evidence that endothelial dysfunction is involved in many of the life-threatening complications of alloSCT, such as sinusoidal obstruction syndrome/venoocclusive disease, transplant-associated thrombotic microangiopathy, and refractory acute graft-versus host disease. This review delineates the role of the endothelium in severe complications after alloSCT and describes the current status of search for biomarkers predicting endothelial complications, including markers of endothelial vulnerability and markers of endothelial injury. Finally, implications of our current understanding of transplant-associated endothelial pathology for prevention and management of complications after alloSCT are discussed.

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Section: Adjusting Anti-neoplastic and Immunosuppressive Regimens To Endothelial Cell Functionmentioning

confidence: 99%

Endothelial cell dysfunction: a key determinant for the outcome of allogeneic stem cell transplantation

Luft

Dreger

Radujkovic

2021

Bone Marrow Transplant

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“…In the revised EBMT criteria, hyperbilirubinemia remains an obligatory marker for the diagnosis of classic SOS/VOD. However, we have observed SOS/VOD in patients with normal to low bilirubin levels, including after RIC allo-HCT, and in patients with late-onset SOS/VOD [ 31 , 42 , 67 – 70 ], suggesting that hyperbilirubinemia may not be obligatory for this group. Recent retrospective analyses that compared the characteristics of classic and late-onset SOS/VOD found that 30% of patients had late-onset SOS/VOD, refractory thrombocytopenia was present in up to 42% of patients with classic SOS/VOD, and 25% of patients with late-onset SOS/VOD did not have hyperbilirubinemia [ 69 ].…”

Section: Diagnostic Criteria For Sos/vodmentioning

confidence: 82%

“…The risk for SOS/VOD with busulfan is presumably dose-dependent; a Korean study demonstrated that a dose greater than 9.6 mg/kg significantly increased the risk for SOS/VOD [ 29 , 36 ], while a lower-dose busulfan regimen was less strongly associated with the development of SOS/VOD in an auto-HCT setting despite the use of an MAC regimen [ 37 – 40 ]. However, SOS/VOD developed despite reduced intensity conditioning (RIC) regimens in 1.6% to 8.9% of patients, and SOS/VOD reportedly developed later in patients with lower bilirubin levels, when these patients were compared to patients who received standard MAC regimens [ 28 , 34 , 41 , 42 ]. In the recent Harmony trial that analyzed the role of defibrotide in preventing the development of SOS/VOD in high-risk or very high-risk patients, eligibility criteria included an MAC regimen involving at least two alkylators or TBI plus at least one alkylator ( ClinicalTrials.gov identifier: NCT02851407).…”

Section: Risk Factors For Sos/vodmentioning

confidence: 99%

Hepatic sinusoidal obstruction syndrome/veno-occlusive disease after hematopoietic cell transplantation: historical and current considerations in Korea

Yoon

Choi

Won

2021

Korean J Intern Med

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Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a rare but severe complication of hematopoietic cell transplantation (HCT) showing high mortality. Multiple risk factors for SOS/VOD were identified, but it is often confused with other hepatic complications due to nonspecific clinical features. Therefore, diagnostic and severity criteria have been re vised several times. The European Society of Blood and Marrow Transplantation suggested a new guideline that excludes the standard duration of devel opment within 21 days, emphasizes late-onset SOS/VOD, and suggests the im portance of Doppler ultrasonography. The severity criteria were further subdivided for guidance to begin active treatment using defibrotide which was approved in Korea since 2016. In a phase 3 trial, defibrotide had superior 100-day survival, compared to best available treatments (38.2% vs. 25.0%). Although several studies of SOS/VOD in Korean patients have been performed after the implementation of HCT, most involved small number of pediatric patients. Recently, the Korean Society of Blood and Marrow Transplantation investigated the incidence of SOS/VOD in the Kore an population, and several influential studies of adult patients were published. Here, we summarize recent issues regarding the mechanism, diagnosis, severity criteria, prevention, and treatments of SOS/VOD in Korean patients, as well as recent analyses of nationwide incidence.

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“…Veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) 2-60% [16,17,152,153] Triad of weight gain (often ascites), right upper quadrant pain or hepatomegaly, and elevated bilirubin [16,17] Fluid retention and ascites, jaundice, weight gain (≥ 5% Onset usually within 120 days after HSCT [19,155] DAH: Fever, dyspnea, and hypoxemia; occurs within 30 days after HSCT and within 5 days of neutrophil engraftment [19] Mortality: [18] Overall: Another of the organ-specific EIS, idiopathic pulmonary syndrome (IPS), is an umbrella term to describe any noninfectious disorder of the lungs characterized by multifocal acute lung injury, shortness of breath, cough, and hypoxemia that occurs within the first four months after HSCT [18]. The pathophysiology of IPS is not completely understood [12], and responses to high doses of corticosteroids are suboptimal [19].…”

Section: Clinical Outcomesmentioning

confidence: 99%

Role of the lectin pathway of complement in hematopoietic stem cell transplantation-associated endothelial injury and thrombotic microangiopathy

Gavriilaki

Schwaeble

et al. 2021

Exp Hematol Oncol

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Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a life-threatening syndrome that occurs in adult and pediatric patients after hematopoietic stem cell transplantation. Nonspecific symptoms, heterogeneity within study populations, and variability among current diagnostic criteria contribute to misdiagnosis and underdiagnosis of this syndrome. Hematopoietic stem cell transplantation and associated risk factors precipitate endothelial injury, leading to HSCT-TMA and other endothelial injury syndromes such as hepatic veno-occlusive disease/sinusoidal obstruction syndrome, idiopathic pneumonia syndrome, diffuse alveolar hemorrhage, capillary leak syndrome, and graft-versus-host disease. Endothelial injury can trigger activation of the complement system, promoting inflammation and the development of endothelial injury syndromes, ultimately leading to organ damage and failure. In particular, the lectin pathway of complement is activated by damage-associated molecular patterns (DAMPs) on the surface of injured endothelial cells. Pattern-recognition molecules such as mannose-binding lectin (MBL), collectins, and ficolins—collectively termed lectins—bind to DAMPs on injured host cells, forming activation complexes with MBL-associated serine proteases 1, 2, and 3 (MASP-1, MASP-2, and MASP-3). Activation of the lectin pathway may also trigger the coagulation cascade via MASP-2 cleavage of prothrombin to thrombin. Together, activation of complement and the coagulation cascade lead to a procoagulant state that may result in development of HSCT-TMA. Several complement inhibitors targeting various complement pathways are in clinical trials for the treatment of HSCT-TMA. In this article, we review the role of the complement system in HSCT-TMA pathogenesis, with a focus on the lectin pathway.

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Incidence, Predictors, and Outcomes of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation

Cited by 20 publications

References 31 publications

Endothelial cell dysfunction: a key determinant for the outcome of allogeneic stem cell transplantation

Endothelial cell dysfunction: a key determinant for the outcome of allogeneic stem cell transplantation

Hepatic sinusoidal obstruction syndrome/veno-occlusive disease after hematopoietic cell transplantation: historical and current considerations in Korea

Role of the lectin pathway of complement in hematopoietic stem cell transplantation-associated endothelial injury and thrombotic microangiopathy

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