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

Published on Mar 1, 2020in Biology of Blood and Marrow Transplantation3.599
· DOI :10.1016/j.bbmt.2019.10.024
Clinton W. Lewis (Auckland City Hospital), Haesook T. Kim57
Estimated H-index: 57
(Harvard University)
+ 13 AuthorsVincent T. Ho71
Estimated H-index: 71
(Harvard University)
Abstract
ABSTRACT fludarabine with intravenous busulfan at doses of 3.2 mg/kg (Flu/Bu1) or 6.4mg/kg (Flu/Bu2) Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious complication of hematopoietic stem cell transplantation (HCT) that is felt to be triggered, at least in part, by damage to the liver sinusoidal endothelium from cytotoxic conditioning regimens. Accordingly, the incidence of VOD/SOS after reduced-intensity conditioning (RIC) HCT is low compared with myeloablative transplantation, and the natural history, risk factors, and outcomes of VOD/SOS after RIC have not been well characterized. We retrospectively reviewed 1583 consecutive patients receiving RIC HCT at the Dana-Farber Cancer Institute between 2007 and 2017 and ascertained 26 cases of VOD/SOS. The median day of VOD/SOS onset was 26 days (range, 5 to 48) and the cumulative incidence at day 50 was 1.6% (95% confidence interval [CI], 1.1% to 2.4%). Day 100 nonrelapse mortality rate was 23% in the VOD/SOS cohort compared with 6.4% in patients without VOD/SOS (P = .006). Cumulative incidence of VOD/SOS at day 50 was 3.1% after RIC regimen with Flu/Bu2 ± ATG (busulfan dose 6.4 mg/kg), compared with 0.15% after Flu/Bu1 ± ATG (busulfan dose 3.2 mg/kg) (P = .0002); the incidence rate was 2.1% after RIC HCT with sirolimus-containing graft-versus-host disease prophylaxis, compared with 0.8% for RIC without sirolimus (P = .06). Significant risk factors identified in multivariable analysis for the development of VOD/SOS were sirolimus use (hazard ratio [HR], 5.1; 95% CI, 1.8 to 14.2; P = .002) and RIC regimen with Flu/Bu2 ± ATG (HR, 34; 95% CI, 4.5 to 252; P
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References33
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#1Mohamad Mohty (University of Paris)H-Index: 54
#2Florent Malard (University of Paris)H-Index: 17
Last. Enric CarrerasH-Index: 45
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Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life-threatening complication that can develop after hematopoietic cell transplantation (HCT). While SOS/VOD may resolve within a few weeks in the majority of patients with mild-to-moderate disease, the most severe forms result in multiorgan dysfunction and are associated with a high mortality rate (>80%). Therefore, careful surveillance may allow early detection of SOS/VOD, particularly as the lice...
4 CitationsSource
#1Paul G. Richardson (Harvard University)H-Index: 156
#2Saurabh Aggarwal SH-Index: 13
Last. Selim Corbacioglu (University of Regensburg)H-Index: 15
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Veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT) conditioning or high-dose nontransplant chemotherapy. VOD/SOS with multi-organ dysfunction (MOD) is associated with a mortality rate of > 80%. Defibrotide (25 mg/kg/day) is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post HSCT in the United States and to treat severe hepatic VOD/SOS in patients ...
4 CitationsSource
#1Lindsey E. Roeker (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 7
#2Haesook T. Kim (Harvard University)H-Index: 57
Last. Vincent T. Ho (Brigham and Women's Hospital)H-Index: 71
view all 13 authors...
Abstract Hepatic veno-occlusive disease (VOD), or sinusoidal obstruction syndrome (SOS), is a serious complication of hematopoietic stem cell transplantation (HSCT) with mortality in its severe form exceeding 80%. Although the incidence of VOD/SOS has fallen with contemporary transplantation practices, the increasing use of inotuzumab, the return of gemtuzumab, and the popularity of pharmacokinetic-guided high-dose busulfan may impact incidence. Early intervention with defibrotide improves survi...
4 CitationsSource
#1Farhad Khimani (USF: University of South Florida)H-Index: 3
#2George B. McDonald (Fred Hutchinson Cancer Research Center)H-Index: 69
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Sirolimus-based graft vs. host disease (GVHD) prophylaxis is associated with higher incidence of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after allogeneic hematopoietic cell transplantation (HCT). However, whether the clinical manifestations and prognosis of VOD/SOS differs when diagnosed in the setting of sirolimus-based GVHD prophylaxis is not well studied. To address this question, we examined presenting features and treatment outcome of VOD/SOS cases identified in a l...
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Abstract A risk score identifying patients at high risk for veno-occlusive disease (VOD) may aid efforts to study preventive strategies for this uncommon complication of hematopoietic cell transplantation (HCT). Patients receiving a first allogeneic HCT between 2008 and 2013 as reported to the Center for International Blood and Marrow Transplant Research (N = 13,097) were randomly divided into training and validation sets. Independent prognostic factors for development of VOD by day +100 after H...
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#1Stephan A. Grupp (Children's Hospital of Philadelphia)H-Index: 57
#2Paul G. Richardson (Harvard University)H-Index: 156
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7047Background: VOD/SOS is an unpredictable, potentially life-threatening complication of HSCT. VOD/SOS with multi-organ dysfunction (MOD) may be associated with > 80% mortality. DF is approved to ...
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#2Florent Malard (University of Paris)H-Index: 17
Last. Enric Carreras (University of Barcelona)H-Index: 45
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The advances in hematopoietic cell transplantation (HCT) over the last decade have led to a transplant-related mortality below 15%. Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of HCT that belongs to a group of diseases increasingly identified as transplant-related, systemic endothelial diseases. In most cases, SOS/VOD resolves within weeks; however, severe SOS/VOD results in multi-organ dysfunction/failure with a mortality rate >80%...
88 CitationsSource
#1Jean-Hugues Dalle (Paris Diderot University)H-Index: 23
#2Sergio A. Giralt (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 40
Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), can develop in a subset of patients, primarily after myeloablative hematopoietic stem cell transplantation, but it also may occur after reduced-intensity conditioning. Severe VOD/SOS, typically characterized by multiorgan failure, has been associated with a mortality rate greater than 80%. Therefore, an accurate and prompt diagnosis of VOD/SOS is essential for early initiation of appropriate therapy to imp...
63 CitationsSource
#1Panagiotis Tsirigotis (HUJI: Hebrew University of Jerusalem)H-Index: 20
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Incidence and risk factors for moderate-to-severe veno-occlusive disease of the liver after allogeneic stem cell transplantation using a reduced intensity conditioning regimen
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