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Paczesny S, Hozo I, Djulbegovic B. Biomarker-derived fast-and-frugal decision tree for preemption of veno-occlusive disease/sinusoidal obstructive syndrome. Blood Adv 2024; 8:5426-5429. [PMID: 39207866 PMCID: PMC11526061 DOI: 10.1182/bloodadvances.2024013670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 08/21/2024] [Accepted: 08/21/2024] [Indexed: 09/04/2024] Open
Affiliation(s)
- Sophie Paczesny
- Departments of Microbiology and Immunology and Pediatrics, Medical University of South Carolina, Charleston, SC
| | - Iztok Hozo
- Department of Mathematics and Actuarial Science, Indiana University Northwest, Gary, IN
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Georgescu D, Lighezan DF, Lascu A, Buzas R, Faur A, Ionita I, Rosca CI, Suceava I, Calamar-Popovici D, Ionita M, Ancusa OE. Hepatic Veno-Occlusive Disease and Colorectal Cancer: Expect the Unexpected. Life (Basel) 2024; 14:845. [PMID: 39063599 PMCID: PMC11277572 DOI: 10.3390/life14070845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 06/15/2024] [Accepted: 06/28/2024] [Indexed: 07/28/2024] Open
Abstract
Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a rare liver vascular condition, potentially life-threatening, with clinical signs of portal hypertension, frequently reported in relation to bone marrow transplantation and possibly in non-transplantation-related chemotherapy. We report the case of a 65-year-old female patient who insidiously developed fatigue, mild tenderness of the right upper abdominal quadrant, hepato-splenomegaly and slight weight gain consecutive to ascites development, as well as persistent elevation of transaminases and mild thrombocytopenia. To note, she had a previous history of colorectal cancer (CRC) with liver metastases and several courses of chemotherapy. Abdominal duplex and elastography measurements made the diagnosis of cirrhosis improbable. A lot of lab work-ups were performed in order to rule out several diseases and conditions. Further, transjugular access was used to perform the measurement of the hepatic venous pressure gradient and liver biopsy that confirmed SOS/VOD. In late 2023, she was diagnosed with endometrial adenocarcinoma, requiring chemotherapy again. At present, the liver condition is stationary, but the prognosis is, however, uncertain. In conclusion, we presented the atypical case of a female patient who developed portal hypertension syndrome associated with the late onset of SOS/VOD, after 5-fluorouracil and oxaliplatin chemotherapy for CRC and liver metastases, subsequently diagnosed with endometrial adenocarcinoma, which posed many diagnostic and therapeutic challenges. Given the potentially bad outcome, an early diagnosis of SOS/VOD in patients receiving drugs of risk is important not only to stratify further risk, but also to initiate an appropriate therapy in order to improve the prognosis.
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Affiliation(s)
- Doina Georgescu
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
| | - Daniel Florin Lighezan
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
| | - Ana Lascu
- Department of Functional Sciences, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Roxana Buzas
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
| | - Alexandra Faur
- Department of Anatomy and Embriology, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania;
| | - Ioana Ionita
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
| | - Ciprian Ilie Rosca
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
| | - Ioana Suceava
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
| | - Despina Calamar-Popovici
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
| | - Mihai Ionita
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
| | - Oana Elena Ancusa
- Department of Internal Medicine I, “V Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (D.G.); (D.F.L.); (R.B.); (I.I.); (C.I.R.); (I.S.); (D.C.-P.); (M.I.); (O.E.A.)
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Wang X, Zhang W, Zhang M, Zhang F, Xiao J, Yin Q, Han H, Li T, Lin G, Zhuge Y. Development of a Drum Tower Severity Scoring (DTSS) system for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome. Hepatol Int 2022; 16:669-679. [PMID: 35023026 PMCID: PMC9174127 DOI: 10.1007/s12072-021-10293-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 12/21/2021] [Indexed: 01/04/2023]
Abstract
BACKGROUND AND AIMS There has been no reliable severity system based on the prognosis to guide therapeutic strategies for patients with pyrrolizidine alkaloid (PA)-induced hepatic sinusoidal obstruction syndrome (HSOS). We aimed to create a novel Drum Tower Severity Scoring (DTSS) system for these patients to guide therapy. METHODS 172 Patients with PA-HSOS who received supportive care and anticoagulation therapy in Nanjing Drum Tower Hospital from January 2008 to December 2020 were enrolled and analyzed retrospectively. These patients were randomized into a training or validation set in a 3:1 ratio. Next, we established and validated the newly developed DTSS system. RESULTS Analysis identified a predictive formula: logit (P) = 0.004 × aspartate aminotransferase (AST, U/L) + 0.019 × total bilirubin (TB, μmol/L) - 0.571 × fibrinogen (FIB, g/L) - 0.093 × peak portal vein velocity (PVV, cm/s) + 1.122. Next, we quantified the above variables to establish the DTSS system. For the training set, the area under the ROC curve (AUC) (n = 127) was 0.787 [95% confidence interval (CI) 0.706-0.868; p < 0.001]. With a lower cut-off value of 6.5, the sensitivity and negative predictive value for predicting no response to supportive care and anticoagulation therapy were 94.7% and 88.0%, respectively. When applying a high cut-off value of 10.5, the specificity was 92.9% and the positive predictive value was 78.3%. For the validation set, the system performed stable with an AUC of 0.808. CONCLUSIONS The DTSS system can predict the outcome of supportive care and anticoagulation in PA-HSOS patients with satisfactory accuracy by evaluating severity, and may have potential significance for guiding therapy.
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Affiliation(s)
- Xuan Wang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
| | - Wei Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
| | - Ming Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
| | - Feng Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
| | - Jiangqiang Xiao
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
| | - Qin Yin
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
| | - Hao Han
- Department of Ultrasound, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
| | - Taishun Li
- Medical Statistical Analysis Center, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
| | - Ge Lin
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
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[Chinese expert consensus on the diagnosis and management of sinusoidal obstruction syndrome after hematopoietic stem cell transplantation (2022)]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2022; 43:177-183. [PMID: 35405774 PMCID: PMC9072071 DOI: 10.3760/cma.j.issn.0253-2727.2022.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Indexed: 11/11/2022]
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Tilmont R, Yakoub-Agha I, Ramdane N, Srour M, Coiteux V, Magro L, Odou P, Simon N, Beauvais D. Impact of Defibrotide in the Prevention of Acute Graft-Versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation. Ann Pharmacother 2022; 56:1007-1015. [PMID: 35016532 DOI: 10.1177/10600280211068177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Defibrotide is indicated for patients who develop severe sinusoidal obstructive syndrome following allogeneic hematopoietic cell transplantation (allo-HCT). Preclinical data suggested that defibrotide carries a prophylactic effect against acute graft-versus-host disease (aGVHD). OBJECTIVE The purpose of this study was to investigate the effect of defibrotide on the incidence and severity of aGVHD. METHODS This single-center retrospective study included all consecutive transplanted patients between January 2014 and December 2018. A propensity score based on 10 predefined confounders was used to estimate the effect of defibrotide on aGVHD via inverse probability of treatment weighting (IPTW). RESULTS Of the 482 included patients, 64 received defibrotide (defibrotide group) and 418 did not (control group). Regarding main patient characteristics and transplantation modalities, the two groups were comparable, except for a predominance of men in the defibrotide group. The median age was 55 years (interquartile range [IQR]: 40-62). Patients received allo-HCT from HLA-matched related donor (28.6%), HLA-matched unrelated donor (50.8%), haplo-identical donor (13.4%), or mismatched unrelated donor (7.0%). Stem cell source was either bone marrow (49.6%) or peripheral blood (50.4%). After using IPTW, exposure to defibrotide was not significantly associated with occurrence of aGVHD (HR = 0.97; 95% CI 0.62-1.52; P = .9) or occurrence of severe aGVHD (HR = 1.89, 95% CI: 0.98-3.66; P = .058). CONCLUSION AND RELEVANCE Defibrotide does not seem to have a protective effect on aGVHD in patients undergoing allo-HCT. Based on what has been reported to date and on these results, defibrotide should not be considered for the prevention of aGVHD outside clinical trials.
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Affiliation(s)
- Rémi Tilmont
- Service des Maladies du Sang, Hôpital Huriez, CHU Lille, Lille, France
| | | | - Nassima Ramdane
- ULR 2694-METRICS: Évaluation des technologies de santé et des pratiques médicales, CHU Lille, University of Lille, Lille, France
| | - Micha Srour
- Service des Maladies du Sang, Hôpital Huriez, CHU Lille, Lille, France
| | - Valérie Coiteux
- Service des Maladies du Sang, Hôpital Huriez, CHU Lille, Lille, France
| | - Léonardo Magro
- Service des Maladies du Sang, Hôpital Huriez, CHU Lille, Lille, France
| | - Pascal Odou
- Institut de Pharmacie, CHU Lille, Lille, France.,ULR 7365-GRITA-Groupe de Recherche sur les formes Injectables et les Technologies Associées, University of Lille, Lille, France
| | - Nicolas Simon
- Institut de Pharmacie, CHU Lille, Lille, France.,ULR 7365-GRITA-Groupe de Recherche sur les formes Injectables et les Technologies Associées, University of Lille, Lille, France
| | - David Beauvais
- CHU de Lille, Université de Lille, INSERM Infinite U1285, Lille, France
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Nabarrete JM, Pereira AZ, Garófolo A, Seber A, Venancio AM, Grecco CES, Bonfim CMS, Nakamura CH, Fernandes D, Campos DJ, Oliveira FLC, Cousseiro FK, Rossi FFP, Gurmini J, Viani KHC, Guterres LF, Mantovani LFAL, Darrigo LG, Albuquerque MIBPE, Brumatti M, Neves MA, Duran N, Villela NC, Zecchin VG, Fernandes JF. Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: children and adolescents. EINSTEIN-SAO PAULO 2021; 19:eAE5254. [PMID: 34909973 PMCID: PMC8664291 DOI: 10.31744/einstein_journal/2021ae5254] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Accepted: 12/10/2020] [Indexed: 11/28/2022] Open
Abstract
The Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Children and Adolescents was developed by dietitians, physicians, and pediatric hematologists from 10 Brazilian reference centers in hematopoietic stem cell transplantation. The aim was to emphasize the importance of nutritional status and body composition during treatment, as well as the main characteristics related to patient´s nutritional assessment. This consensus is intended to improve and standardize nutrition therapy during hematopoietic stem cell transplantation. The consensus was approved by the Brazilian Society of Bone Marrow Transplantation.
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Affiliation(s)
- Juliana Moura Nabarrete
- Hospital Israelita Albert EinsteinSão PauloSPBrazilHospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | - Andrea Z Pereira
- Hospital Israelita Albert EinsteinSão PauloSPBrazilHospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | - Adriana Garófolo
- Universidade Federal de São PauloInstituto de Oncologia PediátricaSão PauloSPBrazilInstituto de Oncologia Pediátrica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
| | - Adriana Seber
- Universidade Federal de São PauloSão PauloSPBrazilUniversidade Federal de São Paulo, São Paulo, SP, Brazil.
| | - Angela Mandelli Venancio
- Hospital Israelita Albert EinsteinSão PauloSPBrazilHospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | - Carlos Eduardo Setanni Grecco
- Universidade de São PauloFaculdade de Medicina de Ribeirão PretoHospital das ClínicasRibeirão PretoSPBrazilHospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
| | - Carmem Maria Sales Bonfim
- Universidade Federal do ParanáHospital de ClínicasCuritibaSPBrazilHospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brazil.
| | - Claudia Harumi Nakamura
- Universidade Federal de São PauloInstituto de Oncologia PediátricaSão PauloSPBrazilInstituto de Oncologia Pediátrica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
| | - Daieni Fernandes
- Santa Casa de Misericórdia de Porto AlegrePorto AlegreRSBrazilSanta Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil.
| | - Denise Johnsson Campos
- Universidade Federal do ParanáHospital de ClínicasCuritibaSPBrazilHospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brazil.
| | - Fernanda Luisa Ceragioli Oliveira
- Universidade Federal de São PauloEscola Paulista de MedicinaSão PauloSPBrazilEscola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
| | - Flávia Krüger Cousseiro
- Santa Casa de Misericórdia de Porto AlegrePorto AlegreRSBrazilSanta Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil.
| | - Flávia Feijó Panico Rossi
- Hospital Israelita Albert EinsteinSão PauloSPBrazilHospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | - Jocemara Gurmini
- Universidade Federal do ParanáHospital de ClínicasCuritibaSPBrazilHospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brazil.
| | - Karina Helena Canton Viani
- Universidade de São PauloFaculdade de MedicinaHospital das ClínicasSão PauloSPBrazilInstituto da Criança, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
| | - Luciana Fernandes Guterres
- Santa Casa de Misericórdia de Porto AlegrePorto AlegreRSBrazilSanta Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil.
| | | | - Luiz Guilherme Darrigo
- Universidade de São PauloFaculdade de Medicina de Ribeirão PretoHospital das ClínicasRibeirão PretoSPBrazilHospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
| | - Maria Isabel Brandão Pires e Albuquerque
- Instituto Nacional de Câncer José Alencar Gomes da SilvaRio de JaneiroRJBrazilInstituto Nacional de Câncer José Alencar Gomes da Silva - INCA, Rio de Janeiro, RJ, Brazil.
| | - Melina Brumatti
- Hospital Israelita Albert EinsteinSão PauloSPBrazilHospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | - Mirella Aparecida Neves
- Universidade Federal do ParanáHospital de ClínicasCuritibaSPBrazilHospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brazil.
| | - Natália Duran
- Hospital de Câncer de BarretosBarretosSPBrazilHospital de Câncer de Barretos, Barretos, SP, Brazil.
| | - Neysimelia Costa Villela
- Hospital de Câncer de BarretosBarretosSPBrazilHospital de Câncer de Barretos, Barretos, SP, Brazil.
| | - Victor Gottardello Zecchin
- Universidade Federal de São PauloInstituto de Oncologia PediátricaSão PauloSPBrazilInstituto de Oncologia Pediátrica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
| | - Juliana Folloni Fernandes
- Hospital Israelita Albert EinsteinSão PauloSPBrazilHospital Israelita Albert Einstein, São Paulo, SP, Brazil.
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Yoon JH, Choi CW, Won JH. Hepatic sinusoidal obstruction syndrome/veno-occlusive disease after hematopoietic cell transplantation: historical and current considerations in Korea. Korean J Intern Med 2021; 36:1261-1280. [PMID: 34555279 PMCID: PMC8588980 DOI: 10.3904/kjim.2021.082] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 04/28/2021] [Indexed: 12/14/2022] Open
Abstract
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 revised several times. The European Society of Blood and Marrow Transplantation suggested a new guideline that excludes the standard duration of development within 21 days, emphasizes late-onset SOS/VOD, and suggests the importance 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 Korean 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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Affiliation(s)
- Jae-Ho Yoon
- Department of Hematology, Catholic Hematology Hospital and Leukemia Research Institute, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Chul Won Choi
- Division of Hematology and Oncology, Department of Internal Medicine, Korea University Guro Hospital, Seoul,
Korea
| | - Jong-Ho Won
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul,
Korea
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Gómez-Centurión I, Bailén R, Oarbeascoa G, Muñoz C, Luque AÁ, Boyra ME, Calleja E, Rincón D, Dorado N, Barzallo P, Anguita J, Díez-Martín JL, Kwon M. Transjugular Intrahepatic Portosystemic Shunt for Very Severe Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) after Unmanipulated Haploidentical Hematopoietic Stem Cell Transplantation with Post-transplantation Cyclophosphamide. Biol Blood Marrow Transplant 2020; 26:2089-2097. [PMID: 32791193 DOI: 10.1016/j.bbmt.2020.08.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 07/13/2020] [Accepted: 08/03/2020] [Indexed: 12/12/2022]
Abstract
Hepatic veno-occlusive disease or sinusoidal obstruction syndrome (VOD/SOS) is a threatening complication after both autologous and allogeneic hematopoietic stem cell transplantation (HSCT), with high mortality rates despite early medical treatment, including the use of defibrotide (DF). We retrospectively analyzed 185 unmanipulated haploidentical (haplo-) HSCT with post-transplantation cyclophosphamide as graft-versus-host disease prophylaxis performed consecutively between 2011 and June 2019 in a single center. Seventeen patients (9.2%) were diagnosed with VOD/SOS. Based on revised European Society for Blood and Marrow Transplantation severity criteria, the VOD/SOS cases were classified as mild in 2 patients (11.7%), moderate in 2 (11.7%), severe in 2 (11.7%), and very severe in 11 (64.9%). Thirteen patients (76%) were treated with DF, including all patients with severe or very severe VOD/SOS, except 1 patient with CNS hemorrhage. Sixteen patients (94%) were alive at day +100 after HSCT. Seven patients (41%) with very severe VOD/SOS were treated with transjugular intrahepatic portosystemic shunt (TIPS) owing to rapid clinical or analytical deterioration or refractory hepatorenal syndrome despite medical treatment, including DF. TIPS insertion was performed at a median time since VOD/SOS diagnosis of 4 days (range, 1 to 28 days) without technical complications in any case. The median hepatic venous pressure gradient before and after TIPS treatment was 24 mmHg (range, 14 to 29 mmHg) and 7 mmHg (range, 2 to 11 mmHg), respectively, with a median drop of 16 mmHg (range, 9 to 19 mmHg). Following TIPS insertion, all patients showed clinical improvement with hepatomegaly, ascites, and renal failure resolution, and all showed analytical improvement with reduced alanine aminotransferase (ALT), creatinine, and international normalized ratio values, except for patient 2, whose indication for TIPS was refractory hepatorenal syndrome with a normal ALT level. The 6 patients who had initiated DF before TIPS insertion completed 21 days of treatment. All patients met the criteria for complete remission (CR) at a median of 8 days after TIPS insertion (range, 2 to 82 days). The 100-day overall survival was 100%. For patients with rapid progressive VOD/SOS, early TIPS insertion allowed completion of DF therapy. The use of TIPS together with DF resulted in CR and no associated complications with no VOD/SOS-associated mortality despite high severity. In our experience, timely and individualized use of TIPS significantly improves outcomes of very severe VOD/SOS after haplo-HSCT. Therefore, TIPS should be promptly considered in rapidly progressive cases.
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Affiliation(s)
| | - Rebeca Bailén
- Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Gregorio Marañón Health Research Institute, Madrid, Spain
| | - Gillen Oarbeascoa
- Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Gregorio Marañón Health Research Institute, Madrid, Spain
| | - Cristina Muñoz
- Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Gregorio Marañón Health Research Institute, Madrid, Spain
| | - Arturo Álvarez Luque
- Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Gregorio Marañón Health Research Institute, Madrid, Spain
| | - Miguel Echenagusia Boyra
- Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Department of Interventional Radiology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Enrique Calleja
- Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Department of Interventional Radiology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Diego Rincón
- Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Department of Hepatology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Nieves Dorado
- Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Gregorio Marañón Health Research Institute, Madrid, Spain
| | - Paola Barzallo
- Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Javier Anguita
- Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Gregorio Marañón Health Research Institute, Madrid, Spain
| | - José Luis Díez-Martín
- Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Gregorio Marañón Health Research Institute, Madrid, Spain; Department of Hematology, Universidad Complutense de Madrid, Madrid, Spain
| | - Mi Kwon
- Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Gregorio Marañón Health Research Institute, Madrid, Spain
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Trenker C, Burchert A, Schumacher C, Schäfer JA, Dohse M, Timmesfeld N, Neubauer A, Sohlbach K, Michel C, Görg C. Pathologic Hepatic Contrast-Enhanced Ultrasound Pattern in Patients Undergoing Allogeneic Stem Cell Transplantation. ULTRASOUND IN MEDICINE & BIOLOGY 2020; 46:1865-1871. [PMID: 32499194 DOI: 10.1016/j.ultrasmedbio.2020.03.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Revised: 02/26/2020] [Accepted: 03/03/2020] [Indexed: 06/11/2023]
Abstract
Veno-occlusive disease (VOD) is a severe complication of allogeneic stem cell transplantation (allo-SCT). Its diagnosis is difficult, and ultrasound (US) has not been proven to be of additional diagnostic value. In the work described here, we prospectively analyzed the hepatic contrast-enhanced ultrasound (CEUS) pattern before and after allo-SCT and correlated these results with the pre-allo-SCT VOD risk factors, clinical VOD findings and conventional US findings. Thirty consecutive patients who underwent allo-SCT and had at least one VOD risk factor were studied. B-Mode US and CEUS were longitudinally performed at defined time points before and after allo-SCT. The 1-min hepatic enhancement (OMHE) in CEUS was standardized to splenic enhancement and quantified using optical density (OD) measurement software. A hypo-OMHE was arbitrarily defined as pathologic (pOMHE) if the OD of the liver was less than 90% compared with the mean splenic OD. Twenty-one patients (70%) had a pOMHE, the occurrence of which peaked at day 10 after allo-SCT. The number of pre-treatment VOD risk factors significantly differed between the pathologic and non-pathologic OD groups. Together, patients undergoing allo-SCT frequently exhibit a pathologic hepatic CEUS pattern, which can be quantified by OD measurement and is suggestive of pre-clinical VOD or other hepatic pathologies.
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Affiliation(s)
- Corinna Trenker
- Department of Hematology, Oncology and Immunology, University Hospital Marburg and Philipps University Marburg, Marburg, Germany.
| | - Andreas Burchert
- Department of Hematology, Oncology and Immunology, University Hospital Marburg and Philipps University Marburg, Marburg, Germany
| | - Caren Schumacher
- Interdisciplinary Ultrasound Center, University Hospital Marburg and Philipps University Marburg, Marburg, Germany
| | - Jonas A Schäfer
- Department of Hematology, Oncology and Immunology, University Hospital Marburg and Philipps University Marburg, Marburg, Germany
| | - Marius Dohse
- Department of Hematology, Oncology and Immunology, University Hospital Marburg and Philipps University Marburg, Marburg, Germany
| | - Nina Timmesfeld
- Department of Medical Informatics, Biometrics and Epidemiology, Ruhr University Bochum, Bochum, Germany
| | - Andreas Neubauer
- Department of Hematology, Oncology and Immunology, University Hospital Marburg and Philipps University Marburg, Marburg, Germany
| | - Kristina Sohlbach
- Department of Hematology, Oncology and Immunology, University Hospital Marburg and Philipps University Marburg, Marburg, Germany
| | - Christian Michel
- Department of Hematology, Oncology and Immunology, University Hospital Marburg and Philipps University Marburg, Marburg, Germany
| | - Christian Görg
- Interdisciplinary Ultrasound Center, University Hospital Marburg and Philipps University Marburg, Marburg, Germany
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10
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Inagaki J, Noguchi M, Fukano R. Prognosis of pediatric patients with anicteric and late-onset sinusoidal obstruction syndrome after hematopoietic stem cell transplantation. Pediatr Blood Cancer 2020; 67:e28412. [PMID: 32495502 DOI: 10.1002/pbc.28412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Revised: 04/20/2020] [Accepted: 04/28/2020] [Indexed: 11/11/2022]
Abstract
BACKGROUND Sinusoidal obstruction syndrome (SOS) is a life-threatening complication after hematopoietic stem cell transplantation (HSCT). Most adult patients with SOS present with jaundice, whereas hyperbilirubinemia does not always occur in children. Additionally, while late-onset SOS is rare in adults, 15-20% of SOS cases develop beyond day 30 after HSCT in children. PROCEDURE We investigated the incidence and prognosis of children with anicteric and late-onset SOS. We retrospectively analyzed the data of patients who developed SOS after HSCT conducted at our center between 2000 and 2016. RESULTS A total of 22 patients with a median age of 6.5 years (range: 0-16), including 14 males and eight females, developed SOS. Eight of the twenty-two patients were diagnosed as having anicteric SOS, and nine as having late-onset SOS. Patients with anicteric SOS had significantly lower incidence of SOS-related death at 100 days after HSCT (12.5% vs 64.3%, P = 0.03) and higher 2-year overall survival (OS) rate (60.0% vs 14.3%, P = .04) than patients with icteric SOS. One patient with anicteric SOS died from progression of SOS. There were no significant differences observed in these endpoints between patients who developed SOS before and after 21 days from HSCT. CONCLUSIONS Careful monitoring is needed for the development of SOS even in the absence of jaundice, and even at 3 weeksafter HSCT in children.
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Affiliation(s)
- Jiro Inagaki
- Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan.,Department of Pediatrics, Kitakyushu City Yahata Hospital, Kitakyushu, Japan
| | - Maiko Noguchi
- Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan
| | - Reiji Fukano
- Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan.,Department of Pediatrics, Yamaguchi University Hospital, Ube, Japan
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11
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Zhou CZ, Wang RF, Lv WF, Fu YQ, Cheng DL, Zhu YJ, Hou CL, Ye XJ. Transjugular intrahepatic portosystemic shunt for pyrrolizidine alkaloid-related hepatic sinusoidal obstruction syndrome. World J Gastroenterol 2020; 26:3472-3483. [PMID: 32655270 PMCID: PMC7327784 DOI: 10.3748/wjg.v26.i24.3472] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 04/30/2020] [Accepted: 05/15/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Treatments for hepatic sinusoidal obstruction syndrome (HSOS) are limited.
AIM To evaluate transjugular intrahepatic portosystemic shunting (TIPS) as a treatment for pyrrolidine alkaloid-related HSOS (PA-HSOS).
METHODS This retrospective analysis included patients with PA-HSOS admitted to the First Affiliated Hospital of the University of Science and Technology of China (June 2015 to January 2019). Baseline clinical characteristics and follow-up data were extracted from the medical records. All patients included in this study experienced failure of initial therapy. Patients were divided into the TIPS and conservative treatment groups according to the therapy they received. Liver function, maximal ascites depth, imaging characteristics, pathology findings, and survival were compared between groups.
RESULTS The TIPS group included 37 patients (28 males), and the conservative treatment group included 17 patients (11 males). Baseline characteristics were similar between groups. There were two deaths in the TIPS group and seven deaths in the conservative treatment group during follow-up (3-48 mo). The 3-, 6-, 12- and 24-mo survival rates were 94.6%, 94.6%, 94.6% and 94.6%, respectively, in the TIPS group and 70.6%, 57.8%, 57.8% and 57.8%, respectively, in the conservative treatment group. Kaplan-Meier analysis revealed significantly longer survival for the TIPS group than for the conservative treatment group (P = 0.001). Compared with the pre-treatment value, maximal ascites depth was significantly lower at 1 wk, 2 wk, 1 mo, and 3 mo for the TIPS group (all P < 0.05) but not in the conservative treatment group. Contrast-enhanced computed tomography demonstrated the disappearance of patchy liver enhancement after TIPS. Pathology showed that liver congestion and hepatocyte swelling improved with time after TIPS placement.
CONCLUSION TIPS may achieve better outcomes than conventional symptomatic treatment in patients with PA-HSOS.
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Affiliation(s)
- Chun-Ze Zhou
- Interventional Radiology, Medical College of Shandong University, Jinan 250021, Shandong Province, China
- Interventional Radiology Department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Rui-Feng Wang
- Department of Nephrology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, Shandong Province, China
| | - Wei-Fu Lv
- Interventional Radiology, Medical College of Shandong University, Jinan 250021, Shandong Province, China
- Interventional Radiology Department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Yu-Qin Fu
- Department of Nephrology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, Shandong Province, China
| | - De-Lei Cheng
- Interventional Radiology Department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Yi-Jiang Zhu
- Interventional Radiology Department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Chang-Long Hou
- Interventional Radiology Department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Xian-Jun Ye
- Department of Ultrasound, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
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12
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Cairo MS, Cooke KR, Lazarus HM, Chao N. Modified diagnostic criteria, grading classification and newly elucidated pathophysiology of hepatic SOS/VOD after haematopoietic cell transplantation. Br J Haematol 2020; 190:822-836. [PMID: 32133623 DOI: 10.1111/bjh.16557] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Sinusoidal obstruction syndrome (SOS), previously known as hepatic veno-occlusive disease (VOD), remains a multi-organ system complication following haematopoietic cell transplantation (HCT). When SOS/VOD is accompanied by multi-organ dysfunction, overall mortality rates remain >80%. However, the definitions related to the diagnosis and grading of SOS/VOD after HCT are almost 25 years old and require new and contemporary modifications. Importantly, the pathophysiology of SOS/VOD, including the contribution of dysregulated inflammatory and coagulation cascades as well as the critical importance of liver and vascular derived endothelial dysfunction, have been elucidated. Here we summarise new information on pathogenesis of SOS/VOD; identify modifiable and unmodifiable risk factors for disease development; propose novel, contemporary and panel opinion-based diagnostic criteria and an innovative organ-based method of SOS/VOD grading classification; and review current approaches for prophylaxis and treatment of SOS/VOD. This review will hopefully illuminate pathways responsible for drug-induced liver injury and manifestations of disease, sharpen awareness of risk for disease development and enhance the timely and correct diagnosis of SOS/VOD post-HCT.
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Affiliation(s)
- Mitchell S Cairo
- Departments of, Department of, Pediatrics, New York Medical College, Valhalla, NY, USA.,Department of, Medicine, New York Medical College, Valhalla, NY, USA.,Department of, Pathology, New York Medical College, Valhalla, NY, USA.,Department of, Microbiology and Immunology, New York Medical College, Valhalla, NY, USA.,Department of, Cell Biology & Anatomy, New York Medical College, Valhalla, NY, USA
| | - Kenneth R Cooke
- Department of Oncology, the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
| | - Hillard M Lazarus
- Department of Medicine, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA
| | - Nelson Chao
- Departments of, Department of, Medicine, Duke University, Durham, NC, USA.,Department of, Immunology, Duke University, Durham, NC, USA.,Department of, Pathology, Duke University, Durham, NC, USA
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13
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Liu F, Rong X, Guo H, Xu D, Liu C, Meng L, Yang X, Guo T, Kan X, Song Y. Clinical characteristics, CT signs, and pathological findings of Pyrrolizidine alkaloids-induced sinusoidal obstructive syndrome: a retrospective study. BMC Gastroenterol 2020; 20:30. [PMID: 32019495 PMCID: PMC7001201 DOI: 10.1186/s12876-020-1180-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 01/28/2020] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND One major etiology of hepatic sinusoidal obstruction syndrome (HSOS) in China is the intake of pyrrolizidine alkaloids (PAs). Since PAs-induced HSOS is a rare disease that has not been clearly characterized until now, the aim of this study was to investigate clinical characteristics, CT features, and pathological findings of PA-induced HSOS. METHODS This retrospective cohort study included 116 patients with PAs-induced HSOS and 68 patients with Budd-Chiari syndrome from Jan 2006 to Sep 2016. We collected medical records of the patients, and reviewed image features of CT, and analyzed pathological findings. RESULTS Common clinical manifestations of PAs-induced HSOS were abdominal distention (98.26%), ascites (100%), jaundice (52.94%), abdominal pain (36.36%). Abnormal liver function was observed in most of PAs-induced HSOS. On CT scan, common findings included: ascites, hepatomegaly, the thickening of gallbladder wall, pleural effusion, patchy liver enhancement, and heterogeneous hypoattenuation. Most of the patients had a low ascitic total protein (< 25 g/L) and a high SAAG (≥ 11.0 g/L). In acute stage, pathologic features were massive sinusoidal dilatation, sinusoidal congestion, the extravasation of erythrocytes, hepatocellular necrosis, the accumulation of macrophages, the deposition of hemosiderin. In subacute stage, complete loss of pericentral hepatocytes, sinusoidal dilatation, the deposition of pigment granules were observed. CONCLUSIONS The PAs-induced HSOS patients displayed distinct clinical characteristics, imaging features, and pathological findings, which provided some evidences for the diagnosis of PAs-induced HSOS. TRIAL REGISTRATION ChiCTR-DRD-17010709.
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Affiliation(s)
- Fang Liu
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xinxin Rong
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Hui Guo
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Dong Xu
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Chang Liu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Lingling Meng
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiaoqian Yang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Tingting Guo
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xuefeng Kan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yuhu Song
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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14
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Baladé Martínez L, Cabezuelo MM, Villamañan Bueno E, Rodríguez Martín E, Herrero Ambrosio A. Defibrotide for the treatment of severe hepatic sinusoidal obstruction syndrome: a single-centre experience. Eur J Hosp Pharm 2019; 26:343-346. [PMID: 31798859 DOI: 10.1136/ejhpharm-2018-001575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 05/29/2018] [Accepted: 05/31/2018] [Indexed: 11/04/2022] Open
Abstract
Objectives Determine the effectiveness and cost of defibrotide in patients with severe hepatic sinusoidal obstruction syndrome following haematopoietic stem cell transplantation in a tertiary hospital. Methods A retrospective observational study. Adults or children treated with defibrotide at a mean dose of 6.8 mg/kg every 6 hours, until the total bilirubin levels are normalised, were included. Main endpoint was complete response, defined as normalised total serum bilirubin levels and resolution of multiple organ failure. Secondary endpoints were survival by 100 days post-transplant, influence of risks factors in effectiveness and cost of treatment. Results 51 patients (36 adults and 15 children) received defibrotide; median dose of defibrotide administered was 25.19 mg/kg/day (10.0-100.3). Complete response was achieved in 19 (37.3%) patients. By 100 days post-transplant complete response was achieved in 18 (35.3%) patients and the survival rate was 29 (56.9%) patients. There were no significant differences in effectiveness between adults versus paediatrics and between patients who presented risk factors. The mean cost of treatment per patient was €32 916, mean costs in adults was €104 292 and €17 394 in children. Conclusion Regarding the results of our study, it is convenient to identify the patients who will be able to benefit from this treatment according to clinical conditions, medical history and prognosis. Given the great economic impact of defibrotide, we consider that more cost-effectiveness studies are required. Trial registration number EPA-OD, number LBM-DEF-2016-01.
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15
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Atilla E, Ataca Atilla P, Cengiz Seval G, Bektaş M, Demirer T. Current approach to early gastrointestinal and liver complications of hematopoietic stem cell transplantation. TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 30:122-131. [PMID: 30459131 DOI: 10.5152/tjg.2018.18156] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The gastrointestinal (GI) system is one of the most commonly affected sites during a hematopoietic stem cell transplantation (HSCT) due to toxicities of preparative regimens, the accompanying immunodeficiency, and organ damage caused by graft versus host disease. In this review, we focus on early GI and liver complications following autologous (auto-) and allogeneic (allo-) HSCT and clarify both the risk factors and therapeutic strategies. Early GI and liver complications associated with HSCT remain challenging issues. Despite the improvements in this field during the last decade, treatments for these complications still place a significant burden on both patients and the physicians treating these patients. GI and liver complications remain some of the causes of mortality associated with HSCT. For practicing hematologists, oncologists, and gastroenterologists in this field, the awareness and early diagnosis of the GI complications remain important factors to obtain optimal outcomes in this patient population.
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Affiliation(s)
- Erden Atilla
- Department of Hematology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey
| | - Pınar Ataca Atilla
- Department of Hematology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey
| | - Güldane Cengiz Seval
- Department of Hematology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey
| | - Mehmet Bektaş
- Department of Gastroenterology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey
| | - Taner Demirer
- Department of Hematology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey
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16
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Hong EK, Joo I, Park J, Lee K. Assessment of hepatic sinusoidal obstruction syndrome with intravoxel incoherent motion diffusion-weighted imaging: An experimental study in a rat model. J Magn Reson Imaging 2019; 51:81-89. [PMID: 31094055 DOI: 10.1002/jmri.26790] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 04/29/2019] [Accepted: 04/29/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) parameters may reflect perfusion and diffusion changes in hepatic sinusoidal obstruction syndrome (SOS). PURPOSE To investigate the feasibility of IVIM-DWI in the noninvasive assessment of hepatic SOS in an experimental rat model. STUDY TYPE Animal study. POPULATION/SUBJECTS Forty-four rats were administered different doses (90 or 160 mg/kg) of monocrotaline by gavage either 48 or 72 hours before MRI to induce different degrees of hepatic SOS, and another 10 rats served as controls. FIELD STRENGTH/SEQUENCE 3T scanner, IVIM-DWI using nine b values (0-800 sec/mm2 ). ASSESSMENT Histologically, rats were classified as having none (n = 10), mild (n = 8), moderate (n = 19), or severe SOS (n = 17). The apparent diffusion coefficient (ADC) and IVIM-derived parameters (D: true diffusion coefficient, D*: pseudo-diffusion coefficient, and f: perfusion fraction) of the liver parenchyma were measured. STATISTICAL TESTS IVIM-DWI parameters were compared according to histologic grades of SOS (none, mild, moderate, and severe), and receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic accuracy. RESULTS ADC, D, and f of the liver parenchyma were significantly different according to SOS severity groups (Ps < 0.01) and significantly decreased as SOS severity increased (rho = -0.323, -0.313, and -0.700; P = 0.017, 0.021, and <0.001, respectively). Means of f in none, mild, moderate, and severe SOS were 17.2%, 13.3%, 12.3%, and 11.1%, respectively. Among ADC and IVIM-derived parameters, f provided the highest area under the ROC curves for detecting ≥mild, ≥moderate, and severe SOS (0.991, 0.890, and 0.803, respectively). DATA CONCLUSION IVIM-DWI may be useful in the diagnosis and severity assessment of hepatic SOS. LEVEL OF EVIDENCE 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:81-89.
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Affiliation(s)
- Eun Kyoung Hong
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Juil Park
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Kyoungbun Lee
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
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17
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Ní Chonghaile M, Wolownik K. Identification and Management: Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease Eelated to Hematopoietic Stem Cell Transplantation
. Clin J Oncol Nurs 2019; 22:E7-E17. [PMID: 29350698 DOI: 10.1188/18.cjon.e7-e17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND Sinusoidal obstruction syndrome (SOS), also called hepatic veno-occlusive disease (VOD), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT) that affects about 1 in 7 patients undergoing this procedure. SOS/VOD is caused by the conditioning regimens administered prior to HSCT; in some cases, SOS/VOD results from chemotherapy alone. SOS/VOD usually develops within three weeks following HSCT; however, it can have later onset.
. OBJECTIVES Clearly understanding how SOS/VOD develops may support prompt detection and treatment when the condition arises.
. METHODS Research on identification and management of SOS/VOD is summarized, and data from clinical trials are reviewed.
. FINDINGS This article describes the syndrome, risk factors, signs and symptoms, and appropriate supportive care and treatment. The authors also offer some practical tips for detecting SOS/VOD and providing patient care, as well as the latest information on treating and preventing this condition.
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18
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Yoon JH, Yoo KH, Sung KW, Jung CW, Kim JS, Hahn SM, Kang HJ, Lee JH, Im HJ, Ahn JS, Kook H, Cho B, Lee JW. Validation of treatment outcomes according to revised severity criteria from European Society for Blood and Marrow Transplantation (EBMT) for sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD). Bone Marrow Transplant 2019; 54:1361-1368. [DOI: 10.1038/s41409-019-0492-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 12/30/2018] [Accepted: 02/17/2019] [Indexed: 01/22/2023]
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19
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Quantitative Analysis of CT Images in Patients with Pyrrolizidine Alkaloid-Induced Sinusoidal Obstruction Syndrome. Sci Rep 2019; 9:2179. [PMID: 30778132 PMCID: PMC6379399 DOI: 10.1038/s41598-019-38669-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 01/04/2019] [Indexed: 12/28/2022] Open
Abstract
This study evaluated hepatic lesion volumes on contrast-enhanced computed tomography (CT) images in patients with pyrrolizidine alkaloid-induced sinusoidal obstruction syndrome (PA-SOS) and the association of lesion volume with the clinical severity and prognosis of the disease. Twenty-five patients with PA-SOS were included in this study, and all patients were subjected to a complete CT imaging series. The imaging results were quantitatively analyzed by a threshold-based region growing algorithm. The liver volumes and hepatic lesion volumes of the patients were estimated. Based on clinical presentations, PA-SOS was classified into three categories: mild, moderate and severe. The associations of hepatic lesion volumes with liver function test parameters and the clinical severity and prognosis of the disease were analyzed. Based on estimations using the threshold-based region growing algorithm, hepatic lesion volumes in patients with mild PA-SOS were significantly lower than those in patients with moderate and severe PA-SOS (P < 0.05). The ratio of hepatic lesion volume to liver volume (Ratio) varied based on alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum total bilirubine levels; clinical severity; and disease prognosis, and the differences were statistically significant (P < 0.05). In conclusion, the threshold-based region growing algorithm can be employed to quantitatively analyze enhanced CT images of PA-SOS patients. And the ratio of hepatic lesion volume to liver volume in patients with PA-SOS is associated with a more serious clinical course and a poorer outcome.
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20
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Fulminant hepatitis due to very severe sinusoidal obstruction syndrome (SOS/VOD) after autologous peripheral stem cell transplantation: a case report. BMC Res Notes 2018; 11:436. [PMID: 29970140 PMCID: PMC6029059 DOI: 10.1186/s13104-018-3533-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Accepted: 06/26/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (SOS/VOD), is a potentially fatal complication of allogeneic or autologous hematopoietic stem cell transplantation. A plethora of transplant and patient-related risk factors predispose to SOS/VOD and should be taken into account for prognosis assessment as well as for adequate therapeutic intervention. CASE PRESENTATION We describe the case of a mantle cell lymphoma patient who developed a fulminant hepatitis following oxaliplatin-containing intensive chemotherapy and autologous transplantation. This clinical manifestation was secondary to a very severe SOS/VOD. The patient did not exhibit the usual risk factors and presented a non-classical form with major cytolysis, thus puzzling SOS/VOD diagnosis in this context. CONCLUSION SOS has been previously reported after oxaliplatin-based chemotherapy regimens for colorectal cancers, in particular in patients with colorectal liver metastases. We therefore suspected a potential relationship with oxaliplatin-based regimen as a driver of SOS/VOD in a non-susceptible lymphoma patient. With regards to this case, clinicians and especially intensivists should be aware of this atypical presentation.
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21
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Birch JC, Khatri G, Watumull LM, Arriaga YE, Leyendecker JR. Unintended Consequences of Systemic and Ablative Oncologic Therapy in the Abdomen and Pelvis. Radiographics 2018; 38:1158-1179. [PMID: 29995613 DOI: 10.1148/rg.2018170137] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Human cancers are genetically complex and diverse. Although advances in oncologic therapy aim to define and target unique steps in carcinogenesis, oncologists often rely on less discriminate anticancer therapies that have consequences for normal tissues. Even many of the so-called targeted therapies currently employed can adversely affect normal cells, leading to complications that necessitate dose reductions or cessation of specific therapies. This article explores the unintended consequences of currently employed systemic and ablative anticancer therapies that might manifest at imaging examinations of the abdomen and pelvis, including cytotoxic, molecular targeted, and immunologic agents; ablation; and hematopoietic stem cell transplant. Each of these treatments can have both major and minor unintended effects in the targeted organ(s), in local or adjacent structures, or at distant sites. Timely detection and reporting of adverse consequences of anticancer therapies by the astute imager can result in critical treatment modifications and/or lifesaving interventions; therefore, knowledge of these unintended effects is paramount for radiologists interpreting the results of imaging examinations in cancer patients. ©RSNA, 2018.
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Affiliation(s)
- Julie C Birch
- From the Department of Radiology (J.C.B., G.K., L.M.W., J.R.L.) and Department of Internal Medicine, Division of Hematology/Oncology (Y.E.A.), University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390
| | - Gaurav Khatri
- From the Department of Radiology (J.C.B., G.K., L.M.W., J.R.L.) and Department of Internal Medicine, Division of Hematology/Oncology (Y.E.A.), University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390
| | - Lori M Watumull
- From the Department of Radiology (J.C.B., G.K., L.M.W., J.R.L.) and Department of Internal Medicine, Division of Hematology/Oncology (Y.E.A.), University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390
| | - Yull E Arriaga
- From the Department of Radiology (J.C.B., G.K., L.M.W., J.R.L.) and Department of Internal Medicine, Division of Hematology/Oncology (Y.E.A.), University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390
| | - John R Leyendecker
- From the Department of Radiology (J.C.B., G.K., L.M.W., J.R.L.) and Department of Internal Medicine, Division of Hematology/Oncology (Y.E.A.), University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390
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22
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Increased hepatic FDG uptake on PET/CT in hepatic sinusoidal obstructive syndrome. Oncotarget 2018; 7:69024-69031. [PMID: 27602584 PMCID: PMC5356608 DOI: 10.18632/oncotarget.11816] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Accepted: 08/27/2016] [Indexed: 12/27/2022] Open
Abstract
Purpose Imaging features of sinusoidal obstruction syndrome (SOS), an increasingly common drawback of chemotherapy, were evaluated via 18F-fluorodeoxyglucose (FDG) positron emission tomography computed tomography (PET/CT). Experimental Design This retrospective study was approved by our Institutional Review Board, with a waiver of informed consent. FDG PET/CT studies of 35 patients (male, 24; female, 11; median age, 53.2 years) obtained between January, 2005 and December, 2012 were analyzed before and after systemic chemotherapy. Diagnosis of SOS was based on histologic (n=13) or gadoxetic acid-enhanced MRI (n=22) findings. On PET/CT images, ROIs drawn on non-tumorous liver generated mean standardized uptake value (SUVliver). Total lesion glycolysis of liver (TLGliver) was calculated as: SUVliver × CT-derived hepatic volume. Paired t-test was applied to compare changes before and after SOS. Results Mean (±standard error [SE]) values of hepatic volume (baseline, 1307.7±46.2 cm3; SOS, 1395.4±41.3 cm3; p=0.004), SUVliver (baseline, 2.08±0.06; SOS, 2.27±0.07; p=0.02), and TLGliver (baseline, 2697.5±114.5; SOS, 3170.2±134.2; p=0.001) significantly increased with development of SOS. In contrast, mean SUVaorta was unchanged (baseline, 1.53±0.04; SOS, 1.50±0.04; p=0.52). Conclusions Hepatic FDG uptake on PET/CT intensified after onset of SOS and thus may be an inappropriate reference in this setting, potentially skewing chemotherapeutic responses gauged by lesion-to-liver SUV ratio.
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23
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Corbacioglu S, Carreras E, Ansari M, Balduzzi A, Cesaro S, Dalle JH, Dignan F, Gibson B, Guengoer T, Gruhn B, Lankester A, Locatelli F, Pagliuca A, Peters C, Richardson PG, Schulz AS, Sedlacek P, Stein J, Sykora KW, Toporski J, Trigoso E, Vetteranta K, Wachowiak J, Wallhult E, Wynn R, Yaniv I, Yesilipek A, Mohty M, Bader P. Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in pediatric patients: a new classification from the European society for blood and marrow transplantation. Bone Marrow Transplant 2018; 53:138-145. [PMID: 28759025 PMCID: PMC5803572 DOI: 10.1038/bmt.2017.161] [Citation(s) in RCA: 224] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Revised: 03/22/2017] [Accepted: 05/29/2017] [Indexed: 12/21/2022]
Abstract
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%. A timely diagnosis of SOS/VOD is of critical importance, given the availability of therapeutic options with favorable tolerability. Current diagnostic criteria are used for adults and children. However, over the last decade it has become clear that SOS/VOD is significantly different between the age groups in terms of incidence, genetic predisposition, clinical presentation, prevention, treatment and outcome. Improved understanding of SOS/VOD and the availability of effective treatment questions the use of the Baltimore and Seattle criteria for diagnosing SOS/VOD in children. The aim of this position paper is to propose new diagnostic and severity criteria for SOS/VOD in children on behalf of the European Society for Blood and Marrow Transplantation.
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Affiliation(s)
- S Corbacioglu
- Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany
| | - E Carreras
- Hematology Department, Josep Carreras Foundation & Leukemia Research Institute, Hospital Clínic, Barcelona, Spain
| | - M Ansari
- Hemato-Oncology Unit, Department of Pediatrics, University Hospital of Geneva, Geneva, Switzerland
| | - A Balduzzi
- Pediatric Clinic, University of Milano-Bicocca, San Gerardo Hospital, Milan, Italy
| | - S Cesaro
- Department of Pediatric Oncohematology, Giambattista Rossi University Hospital, Verona, Italy
| | - J-H Dalle
- Department of Hematology and Immunology, Hospital Robert Debre, Paris 7-Paris Diderot University, Paris, France
| | - F Dignan
- Department of Clinical Haematology, Manchester Royal Infirmary, Manchester, UK
| | - B Gibson
- Royal Hospital for Sick Children, Glasgow, UK
| | - T Guengoer
- Division of Blood and Marrow Transplantation, University Children’s Hospital, Zurich, Switzerland
| | - B Gruhn
- Department of Pediatrics, University Hospital of Jena, Jena, Germany
| | - A Lankester
- Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
| | - F Locatelli
- Department of Pediatric Hematology and Oncology, University of Pavia, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
| | - A Pagliuca
- Department of Haematology, King’s College Hospital, London, UK
| | - C Peters
- Department of Pediatrics, St Anna Kinderspital, Vienna, Austria
| | - P G Richardson
- Division of Hematologic Malignancy, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - A S Schulz
- Department of Pediatrics, University Children’s Hospital, Ulm, Germany
| | - P Sedlacek
- Department of Pediatrics, University Hospital Motol, Prague, Czech Republic
| | - J Stein
- Schneider Children's Medical Center of Israel and Sackler Faculty of Medicine, University of Tel Aviv, Tel Aviv, Israel
| | - K-W Sykora
- Pediatric Hematology-Oncology, Children’s Hospital, Medical School, Hannover, Germany
| | | | - E Trigoso
- University Hospital and Polytechnic La Fe, Valencia, Spain
| | - K Vetteranta
- Children’s Hospital, University of Helsinki, Helsinki, Finland
| | - J Wachowiak
- Department of Pediatric Hematology, Oncology and Hematopoietic Stem Cell Transplantation, University of Medical Sciences, Poznan, Poland
| | - E Wallhult
- Section of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - R Wynn
- Royal Manchester Children’s Hospital, Manchester, UK
| | - I Yaniv
- Schneider Children's Medical Center of Israel and Sackler Faculty of Medicine, University of Tel Aviv, Tel Aviv, Israel
| | - A Yesilipek
- Pediatric Stem Cell Transplantation Unit, Bahçeşehir University School of Medicine, Istanbul, Turkey
| | - M Mohty
- Hôpital Saint-Antoine, APHP, Université Pierre & Marie Curie, INSERM UMRS 938, Paris, France
| | - P Bader
- Division for Stem Cell Transplantation and Immunology, Department for Children and Adolescents, University Hospital, Goethe University, Frankfurt/Main, Germany
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24
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Sinusoidal Obstruction Syndrome During Maintenance Therapy for Acute Lymphoblastic Leukemia With 6-Mercaptopurine and Methotrexate: A Pediatric Case Report. J Pediatr Hematol Oncol 2017; 39:e454-e455. [PMID: 28085749 DOI: 10.1097/mph.0000000000000776] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
We report a case of a child with pre-B cell acute lymphoblastic leukemia undergoing maintenance chemotherapy with 6-mercaptopurine and methotrexate (MTX) who developed sinusoidal obstruction syndrome after being treated with ciprofloxacin for BK viremia. This case represents a rare complication of maintenance therapy with MTX and 6-mercaptopurine, and suggests a drug interaction between ciprofloxacin and MTX.
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25
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Sinusoidal Obstruction Syndrome During Chemotherapy of Pediatric Cancers and its Successful Management With Defibrotide. J Pediatr Hematol Oncol 2017; 39:e373-e376. [PMID: 28859028 DOI: 10.1097/mph.0000000000000958] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Sinusoidal obstruction syndrome (SOS) is a life-threatening complication generally occurring after hematopoietic stem cell transplantation. SOS after standard dose chemotherapy in malignancies is rare. Between the year 1995 and 2016, 414 patients were diagnosed with acute lymphoblastic leukemia and 113 patients were diagnosed with Wilms tumor in our institution. Among these patients, 4 patients with acute lymphoblastic leukemia (0.96%) and 2 patients with Wilms tumor (1.7%) developed SOS during treatment. SOS behaves like a local disseminated intravascular coagulation. Defibrotide has proved to be effective in SOS. In this article, we report our experience with defibrotide in SOS.
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26
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Bajwa RPS, Mahadeo KM, Taragin BH, Dvorak CC, McArthur J, Jeyapalan A, Duncan CN, Tamburro R, Gehred A, Lehmann L, Richardson P, Auletta JJ, Woolfrey AE. Consensus Report by Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplantation Consortium Joint Working Committees: Supportive Care Guidelines for Management of Veno-Occlusive Disease in Children and Adolescents, Part 1: Focus on Investigations, Prophylaxis, and Specific Treatment. Biol Blood Marrow Transplant 2017; 23:1817-1825. [PMID: 28754544 DOI: 10.1016/j.bbmt.2017.07.021] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Accepted: 07/20/2017] [Indexed: 12/13/2022]
Abstract
Veno-occlusive disease (VOD) is a common and potentially fatal complication in children undergoing hematopoietic cell transplantation (HCT). It occurs in about one-third of all patients undergoing transplantation and is fatal in 50% of patients with severe disease. Early intervention and specific treatment with defibrotide are associated with improved outcomes. However, there is a lack of supportive care guidelines for management of the multiorgan dysfunction seen in most cases. There is high variability in the management of VOD, which may contribute to the increased morbidity and mortality. Although there is ample research in the specific treatment of VOD, there is paucity of literature regarding the management of ascites, transfusions requirements, fluids and electrolyte dysfunction, delirium, and investigations in children with VOD. The joint working committees of the Pediatric Acute Lung Injury and Sepsis Investigators and the Pediatric Blood and Marrow Transplantation Consortium collaborated to develop a series of evidence-based supportive care guidelines for management of VOD. The quality of evidence was rated and recommendations were made using Grading of Recommendations, Assessment, Development and Evaluation criteria. This manuscript is part 1 of the series and focuses on the need to develop these guidelines; methodology used to establish the guidelines; and investigations needed for diagnosis, prophylaxis, and treatment of VOD in children.
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Affiliation(s)
- Rajinder P S Bajwa
- Division of Hematology/Oncology/Blood and Marrow Transplantation, Nationwide Children's Hospital, Columbus, Ohio.
| | - Kris M Mahadeo
- Division of Pediatric Blood and Marrow Transplantation, The University of Texas, MD Anderson Children's Cancer Hospital, Houston, Texas
| | - Benjamin H Taragin
- Department of Pediatric Radiology, Children's Hospital at Montefiore, Bronx, New York
| | - Christopher C Dvorak
- Division of Pediatric Allergy, Immunology, and Bone Marrow Transplant, University of California San Francisco, Benioff Children's Hospital, San Francisco, California
| | - Jennifer McArthur
- Department of Pediatric Critical Care Medicine St Jude Children's Research Hospital, Memphis, Tennessee
| | - Asumthia Jeyapalan
- Division of Pediatric Critical Care Medicine, University of Miami- Miller School of Medicine, Miami, Florida
| | - Christine N Duncan
- Division of Pediatric Stem Cell Transplant, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Robert Tamburro
- Division of Pediatric Critical Care Medicine, Pennsylvania University, Penn State Hershey Children's Hospital, Hershey, PA
| | - Alison Gehred
- Medical Library division, Nationwide Children's Hospital, Columbus, Ohio
| | - Leslie Lehmann
- Division of Pediatric Stem Cell Transplant, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Paul Richardson
- Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Jeffery J Auletta
- Division of Hematology/Oncology/Blood and Marrow Transplantation, Nationwide Children's Hospital, Columbus, Ohio; Division of Infectious Diseases, Nationwide Children's Hospital, Columbus
| | - Ann E Woolfrey
- Fred Hutchinson Cancer Research Center and University of Washington, Seattle, Washington
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27
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Evaluation of thromboelastometry parameters as predictive markers for sinusoidal obstruction syndrome in patients undergoing allogeneic stem cell transplantation for acute leukaemia. Oncotarget 2017; 8:60001-60014. [PMID: 28938703 PMCID: PMC5601799 DOI: 10.18632/oncotarget.18499] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Accepted: 05/29/2017] [Indexed: 12/17/2022] Open
Abstract
Hepatic sinusoidal obstruction syndrome (previously named veno-occlusive disease, SOS/VOD) is a serious complication of allogeneic stem cell transplantation (HSCT). Early identification of patients at risk of SOS/VOD may possibly improve the outcome and reduce mortality. Rotation thromboelastometry (ROTEM) is global assay allowing for the precise assessment of both bleeding and thrombotic conditions, however, its usefulness in patients undergoing HSCT for acute leukaemia has not been studied. We evaluated the thromboelastometry parameters in patients undergoing allogeneic HSCT for acute leukaemia to identify candidate biomarkers of SOS/VOD occurrence. ROTEM assays (INTEM, EXTEM, FIBTEM, APTEM) were performed on day -10, on the day of stem cell infusion (day 0) and on days +12 and +28 post-HSCT. The diagnosis of SOS/VOD was based on the Baltimore criteria. Seven patients (26%) developed SOS/VOD. On day +12, the patients with SOS/VOD had statistically significant longer INTEM-CT (clotting time, 199 ± 33.41vs166 ± 23.65s, p = 0.0033), EXTEM-CT (69.5 ± 6.39vs.52 ± 3.42s, p = 0.0139) and FIBTEM-CT (69.5 ± 22.75vs. 50.8 ± 14.31s, p = 0.0124) compared to SOS/VOD (-). ROC curve on day +12 indicated a cut-off value of 179s in INTEM-CT (AUC = 0.91), 69s in EXTEM-CT (AUC = 0.90) and 102s in FIBTEM-CT (AUC = 0.82) for the prediction of SOS/VOD. This is the first study evaluating the usefulness of ROTEM assays in the early detection of haemostasis abnormalities predictive of SOS/VOD development in patients undergoing HSCT for acute leukemia. Patients with SOS/VOD had a significant delay in the initiation of thrombin formation in the analysed ROTEM assays. The utility of ROTEM assays in the optimal management of patients undergoing HSCT should be clarified in further prospective studies.
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28
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Pichler H, Horner K, Engstler G, Poetschger U, Glogova E, Karlhuber S, Martin M, Eibler W, Witt V, Holter W, Matthes-Martin S. Cost-Effectiveness of Defibrotide in the Prophylaxis of Veno-Occlusive Disease after Pediatric Allogeneic Stem Cell Transplantation. Biol Blood Marrow Transplant 2017; 23:1128-1133. [PMID: 28359910 DOI: 10.1016/j.bbmt.2017.03.022] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Accepted: 03/18/2017] [Indexed: 11/29/2022]
Abstract
Veno-occlusive disease (VOD) remains a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Prophylactic use of defibrotide (DF) might further reduce VOD rates but has no impact on the incidence of severe VOD or VOD-associated mortality. We investigated the cost-effectiveness of prophylactic DF according to the British Committee for Standards in Haematology/British Society for Blood and Marrow Transplantation guidelines in 348 children who underwent transplantation between 2001 and 2014 in our hospital, 138 of whom were at risk for VOD. The VOD incidence was 7.4% for the total cohort. Patients at risk had a higher incidence of VOD compared with patients without risk factors (15.2% versus 2.4%, P < .0001). VOD occurred more often in patients after busulfan-based myeloablative conditioning than in patients after total body irradiation (11.2% versus 3.5%, P = .001). Donor types or the transplantation-related mortality (TRM) risk score did not correlate with VOD incidence. In 81% of patients who responded to therapeutic DF, VOD resolved completely. Overall VOD-associated mortality was .3% for the complete cohort, 3.7% for patients diagnosed with VOD, and 20% for patients with severe VOD. Neither the cumulative incidence of TRM (19% ± 8% versus 17% ± 2%, P = .706) nor the median length of hospitalization differed between patients with VOD and patients without. The median costs per HSCT in patients with VOD were about one-third higher than the overall median costs per transplantation at our institution. The calculated total costs of prophylactic DF treatment for 138 patients at risk was almost 6 times as high as the incremental costs for patients with VOD. We conclude that prophylactic DF for children at risk for VOD is not cost-effective with respect to TRM and length of hospital stay.
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Affiliation(s)
- Herbert Pichler
- St. Anna Children's Hospital, Department of Paediatrics, Medical University of Vienna, Austria.
| | - Karolina Horner
- St. Anna Children's Hospital, Department of Paediatrics, Medical University of Vienna, Austria
| | - Gernot Engstler
- St. Anna Children's Hospital, Department of Paediatrics, Medical University of Vienna, Austria
| | - Ulrike Poetschger
- Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Department of Paediatrics, Medical University of Vienna, Austria
| | - Evgenia Glogova
- Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Department of Paediatrics, Medical University of Vienna, Austria
| | - Susanne Karlhuber
- Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Department of Paediatrics, Medical University of Vienna, Austria
| | | | - Werner Eibler
- St. Anna Children's Hospital, Department of Paediatrics, Medical University of Vienna, Austria
| | - Volker Witt
- St. Anna Children's Hospital, Department of Paediatrics, Medical University of Vienna, Austria
| | - Wolfgang Holter
- St. Anna Children's Hospital, Department of Paediatrics, Medical University of Vienna, Austria
| | - Susanne Matthes-Martin
- St. Anna Children's Hospital, Department of Paediatrics, Medical University of Vienna, Austria
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29
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Cheuk DKL, Anand V, Chiang AKS, Ha SY, Chan GCF. Interventions for treatment of hepatic veno-occlusive disease in patients undergoing hematopoietic stem cell transplantation. Hippokratia 2016. [DOI: 10.1002/14651858.cd009312.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Daniel KL Cheuk
- The University of Hong Kong, Queen Mary Hospital; Department of Pediatrics and Adolescent Medicine; Pokfulam Road Hong Kong China
| | - Vidhu Anand
- University of Minnesota; Department of Medicine; 420 Delaware Street SE Mayo Mail Code 195 Minneapolis MN USA 55455
| | - Alan KS Chiang
- The University of Hong Kong, Queen Mary Hospital; Department of Pediatrics and Adolescent Medicine; 121 Pokfulam Road Hong Kong SAR China
| | - Shau Yin Ha
- The University of Hong Kong, Queen Mary Hospital; Department of Pediatrics and Adolescent Medicine; 121 Pokfulam Road Hong Kong SAR China
| | - Godfrey CF Chan
- The University of Hong Kong, Queen Mary Hospital; Department of Pediatrics and Adolescent Medicine; 121 Pokfulam Road Hong Kong SAR China
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30
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Abstract
Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), represents the most frequent complication in patients in early phase following hematopoietic stem-cell transplantation (HSCT). In its severe form, VOD/SOS can be associated with multiorgan failure and with a mortality rate >80% by day +100. Defibrotide (DF) (a mixture of 90% single-stranded phosphodiester oligonucleotides and 10% double-stranded phosphodiester oligonucleotides derived from controlled depolarization of porcine intestinal mucosal DNA) has been proposed for the treatment of SOS due to its ability to restore thrombo-fibrinolytic balance and protect endothelial cells. The present review highlights why the mechanisms of action of DF allow its successful use in the prevention and treatment of SOS following HSCT.
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Affiliation(s)
- Alessandro Fulgenzi
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| | - Maria Elena Ferrero
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
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31
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Hasle H, Kaspers GJL. Strategies for reducing the treatment-related physical burden of childhood acute myeloid leukaemia - a review. Br J Haematol 2016; 176:168-178. [PMID: 27766626 DOI: 10.1111/bjh.14419] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2016] [Accepted: 08/22/2016] [Indexed: 12/24/2022]
Abstract
Over the last four decades the survival of paediatric patients with acute myeloid leukaemia has gradually increased to 70% in high-income countries. The therapy is very intensive and associated with many acute and long-term side effects. The early death rate has been reduced to 1-4%. The acute toxicity is a limiting factor for improving survival in low-income countries. Transplant is associated with more endocrinological late effects while cardiotoxicity is more common after relapse. Reducing the physical costs of therapy without jeopardizing survival may be accomplished by optimal supportive care, less cardiotoxic anthracyclines, less consolidation courses and strict indications for stem cell transplantation. Analysing scenarios with different frequency of transplantation in first complete remission show similar overall survival rates, indicating that almost all patients can be spared the procedure in first remission. Reducing relapse risk is an effective way of reducing toxicity and more targeted therapy and improved risk group stratifications are needed.
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Affiliation(s)
- Henrik Hasle
- Department of Paediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark
| | - Gertjan J L Kaspers
- Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands.,Academy of Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
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32
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Botti S, Orlando L, Gargiulo G, Cecco VD, Banfi M, Duranti L, Samarani E, Netti MG, Deiana M, Galuppini V, Pignatelli AC, Ceresoli R, Vedovetto A, Rostagno E, Bambaci M, Dellaversana C, Luminari S, Bonifazi F. Veno-occlusive disease nurse management: development of a dynamic monitoring tool by the GITMO nursing group. Ecancermedicalscience 2016; 10:661. [PMID: 27594906 PMCID: PMC4990055 DOI: 10.3332/ecancer.2016.661] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Indexed: 01/17/2023] Open
Abstract
Veno-occlusive disease (VOD) is a complication arising from the toxicity of conditioning regimens that have a significant impact on the survival of patients who undergo stem cell transplantation. There are several known risk factors for developing VOD and their assessment before the start of conditioning regimens could improve the quality of care. Equally important are early identification of signs and symptoms ascribable to VOD, rapid diagnosis, and timely adjustment of support therapy and treatment. Nurses have a fundamental role at the stages of assessment and monitoring for signs and symptoms; therefore, they should have documented skills and training. The literature defines nurses’ areas of competence in managing VOD, but in the actual clinical practice, this is not so clear. Moreover, there is an intrinsic difficulty in managing VOD due to its rapid and often dramatic evolution, together with a lack of care tools to guide nurses. Through a complex evidence-based process, the Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO), cellule staminali emopoietiche e terapia cellulare nursing board has developed an operational flowchart and a dynamic monitoring tool applicable to haematopoietic stem cell transplantation patients, whether they develop this complication or not.
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Affiliation(s)
- Stefano Botti
- Haematology Unit, Arcispedale Santa Maria Nuova-IRCCS Reggio Emilia, Italy
| | - Laura Orlando
- Division of Clinical Haemato-Oncology, Istituto Europeo di Oncologia, Milan, Italy
| | | | - Valentina De Cecco
- Paediatric Haemato-Oncology Unit, Policlinico S Matteo Pavia, Viale Camillo Golgi, 19, 27100 Pavia PV, Italy
| | - Marina Banfi
- BMT Unit, Ospedale Maggiore IRCCS Milano, Milan, Italy
| | - Lorenzo Duranti
- Haematology and BMT Unit, Ospedale Silvestrini, Perugia, Italy
| | | | - Maria Giovanna Netti
- SODc Paediatric Tumours and BMT Unit, Ospedale Pediatrico Meyer Firenze, Florence, Italy
| | - Marco Deiana
- Paediatric Haematology/Oncology Department, IRCCS G Gaslini, Genova, Italy
| | | | | | | | - Alessio Vedovetto
- Paediatric Haemato-Oncology and BMT Unit, Azienda Ospedaliera di Padova, Via Nicolò Giustiniani, 2, 35128 Padova PD, Italy
| | - Elena Rostagno
- Paediatric Haematology/Oncology and BMT Department, Azienda Ospedaliero, Universitaria S Orsola Malpighi, Bologna, Italy
| | - Marilena Bambaci
- Paediatric Haemato-Oncology and BMT Unit , Ospedale Regina Margherita, Torino, Italy
| | | | - Stefano Luminari
- Haematology Unit, Arcispedale Santa Maria Nuova-IRCCS Reggio Emilia, Italy
| | - Francesca Bonifazi
- Haematology and BMT Unit, Azienda Ospedaliero, Universitaria S Orsola Malpighi, Bologna, Italy
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Heterogeneous response to recombinant thrombomodulin by grade of sinusoidal obstructive syndrome after pediatric stem cell transplantation. Bone Marrow Transplant 2016; 51:1543-1545. [DOI: 10.1038/bmt.2016.179] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant 2016; 51:906-12. [PMID: 27183098 PMCID: PMC4935979 DOI: 10.1038/bmt.2016.130] [Citation(s) in RCA: 317] [Impact Index Per Article: 35.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Revised: 03/30/2016] [Accepted: 04/01/2016] [Indexed: 12/15/2022]
Abstract
Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (>80%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation.
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Critically ill allogeneic hematopoietic stem cell transplantation patients in the intensive care unit: reappraisal of actual prognosis. Bone Marrow Transplant 2016; 51:1050-61. [PMID: 27042832 DOI: 10.1038/bmt.2016.72] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Revised: 02/14/2016] [Accepted: 02/17/2016] [Indexed: 12/16/2022]
Abstract
The outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients has significantly improved over the past decade. Still, a significant number of patients require intensive care unit (ICU) management because of life-threatening complications. Literature from the 1990s reported extremely poor prognosis for critically ill allo-HSCT patients requiring ICU management. Recent data justify the use of ICU resources in hematologic patients. Yet, allo-HSCT remains an independent variable associated with mortality. However, outcomes in allo-HSCT patients have improved over time and many classic determinants of mortality have become irrelevant. The main actual prognostic factors are the need for mechanical ventilation, the presence of GvHD and the number of organ failures at ICU admission. Recently, the development of reduced-intensity conditioning regimens, early ICU admission and the increased use of noninvasive ventilation, combined with time effect and general advances in hematology, in allo-HSCT procedures and in ICU management have contributed to improve general outcome. A rational policy of ICU admission triage in these patients is very hard to define, as each decision for ICU admission is a case-by-case decision at patient bedside. The collaboration between hematologists and intensivists is crucial in this context.
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Hematopoietic Stem Cell Transplantation. PATHOLOGY OF TRANSPLANTATION 2016. [PMCID: PMC7124099 DOI: 10.1007/978-3-319-29683-8_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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Sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation: Incidence, risk factors and outcomes. Bone Marrow Transplant 2015; 51:403-9. [DOI: 10.1038/bmt.2015.283] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2015] [Revised: 09/28/2015] [Accepted: 10/16/2015] [Indexed: 01/16/2023]
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Dalle JH, Giralt SA. Hepatic Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation: Risk Factors and Stratification, Prophylaxis, and Treatment. Biol Blood Marrow Transplant 2015; 22:400-9. [PMID: 26431626 DOI: 10.1016/j.bbmt.2015.09.024] [Citation(s) in RCA: 196] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Accepted: 09/24/2015] [Indexed: 12/13/2022]
Abstract
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 improve clinical outcomes. Moreover, some studies have support the use of prophylaxis for patients who are at high risk of developing VOD/SOS. This review summarizes risk factors associated with development of VOD/SOS, including pretransplantation patient characteristics and factors related to stem cell transplantation, that can facilitate patient stratification according to risk. The incidence of VOD/SOS, clinical features, and diagnostic criteria are reviewed. Data on emerging treatment strategies for patients with VOD/SOS are discussed in the context of recent treatment guidelines. Additionally, options for prophylaxis in individuals who are at increased risk are presented. Although historically only those patients with moderate to severe VOD/SOS have been treated, early therapy and prophylaxis may be appropriate for many patients and may have the potential to improve patients' outcomes and survival, including for those with nonsevere disease.
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Affiliation(s)
- Jean-Hugues Dalle
- Department of Paediatric Haematology, Paris Diderot University, Sorbonne Paris Cité, Hôpital Robert Debré, APHP, Paris, France
| | - Sergio A Giralt
- Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York.
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Miyashita T, Nakanuma S, Ahmed AK, Makino I, Hayashi H, Oyama K, Nakagawara H, Tajima H, Takamura H, Ninomiya I, Fushida S, Harmon JW, Ohta T. Ischemia reperfusion-facilitated sinusoidal endothelial cell injury in liver transplantation and the resulting impact of extravasated platelet aggregation. Eur Surg 2015; 48:92-98. [PMID: 27110233 PMCID: PMC4830883 DOI: 10.1007/s10353-015-0363-3] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 09/28/2015] [Accepted: 09/29/2015] [Indexed: 12/13/2022]
Abstract
Background The exact sequence of events leading to ultimate hepatocellular damage following ischemia/reperfusion (I/R) is incompletely understood. In this article, we review a mechanism of organ dysfunction after hepatic I/R or immunosuppressive treatment, in addition to the potential of liver sinusoidal endothelial cell (LSEC) protection and antiplatelet treatment for the suppression of hepatocellular damage. Methods A review of the literature, utilizing PubMed-NCBI, was used to provide information on the components necessary for the development of hepatocellular damage following I/R. Results It is well-established that LSECs damage following hepatic I/R or immunosuppressive treatment followed by extravasated platelet aggregation (EPA) is the root cause of organ dysfunction in liver transplantation. We have classified three phases, from LSECs damage to organ dysfunction, utilizing the predicted pathogenic mechanism of sinusoidal obstruction syndrome. The first phase is detachment of LSECs and sinusoidal wall destruction after LSECs injury by hepatic I/R or immunosuppressive treatment. The second phase is EPA, accomplished by sinusoidal wall destruction. The various growth factors, including thromboxane A2, serotonin, transforming growth factor-beta and plasminogen activator inhibitor-1, released by EPA in the Disse’s space of zone three, induce portal hypertension and the progression of hepatic fibrosis. The third phase is organ dysfunction following portal hypertension, hepatic fibrosis, and suppressed liver regeneration through various growth factors secreted by EPA. Conclusion We suggest that EPA in the space of Disse, initiated by LSECs damage due to hepatic I/R or immunosuppressive treatment, and activated platelets may primarily contribute to liver damage in liver transplantation. Endothelial protective therapy or antiplatelet treatment may be useful in the treatment of hepatic I/R following EPA.
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Affiliation(s)
- T Miyashita
- Department of Gastroenterological Surgery, Kanazawa University Hospital, 13-1 Takaramachi, 920-8641 Kanazawa, Ishikawa Japan
| | - S Nakanuma
- Department of Gastroenterological Surgery, Kanazawa University Hospital, 13-1 Takaramachi, 920-8641 Kanazawa, Ishikawa Japan
| | - A K Ahmed
- Department of Surgery, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224 Baltimore, MD USA
| | - I Makino
- Department of Gastroenterological Surgery, Kanazawa University Hospital, 13-1 Takaramachi, 920-8641 Kanazawa, Ishikawa Japan
| | - H Hayashi
- Department of Gastroenterological Surgery, Kanazawa University Hospital, 13-1 Takaramachi, 920-8641 Kanazawa, Ishikawa Japan
| | - K Oyama
- Department of Gastroenterological Surgery, Kanazawa University Hospital, 13-1 Takaramachi, 920-8641 Kanazawa, Ishikawa Japan
| | - H Nakagawara
- Department of Gastroenterological Surgery, Kanazawa University Hospital, 13-1 Takaramachi, 920-8641 Kanazawa, Ishikawa Japan
| | - H Tajima
- Department of Gastroenterological Surgery, Kanazawa University Hospital, 13-1 Takaramachi, 920-8641 Kanazawa, Ishikawa Japan
| | - H Takamura
- Department of Gastroenterological Surgery, Kanazawa University Hospital, 13-1 Takaramachi, 920-8641 Kanazawa, Ishikawa Japan
| | - I Ninomiya
- Department of Gastroenterological Surgery, Kanazawa University Hospital, 13-1 Takaramachi, 920-8641 Kanazawa, Ishikawa Japan
| | - S Fushida
- Department of Gastroenterological Surgery, Kanazawa University Hospital, 13-1 Takaramachi, 920-8641 Kanazawa, Ishikawa Japan
| | - J W Harmon
- Department of Surgery, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224 Baltimore, MD USA
| | - T Ohta
- Department of Gastroenterological Surgery, Kanazawa University Hospital, 13-1 Takaramachi, 920-8641 Kanazawa, Ishikawa Japan
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Akil A, Zhang Q, Mumaw CL, Raiker N, Yu J, Velez de Mendizabal N, Haneline LS, Robertson KA, Skiles J, Diaz-Ricart M, Carreras E, Renbarger J, Hanash S, Bies RR, Paczesny S. Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 2015; 21:1739-45. [PMID: 26172478 PMCID: PMC4568166 DOI: 10.1016/j.bbmt.2015.07.004] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Accepted: 07/06/2015] [Indexed: 12/11/2022]
Abstract
Reliable, noninvasive methods for diagnosing and prognosing sinusoidal obstruction syndrome (SOS) early after hematopoietic cell transplantation (HCT) are needed. We used a quantitative mass spectrometry-based proteomics approach to identify candidate biomarkers of SOS by comparing plasma pooled from 20 patients with and 20 patients without SOS. Of 494 proteins quantified, we selected 6 proteins (L-Ficolin, vascular cell adhesion molecule-1 [VCAM1], tissue inhibitor of metalloproteinase-1, von Willebrand factor, intercellular adhesion molecule-1, and CD97) based on a differential heavy/light isotope ratio of at least 2 fold, information from the literature, and immunoassay availability. Next, we evaluated the diagnostic potential of these 6 proteins and 5 selected from the literature (suppression of tumorigenicity-2 [ST2], angiopoietin-2 (ANG2), hyaluronic acid [HA], thrombomodulin, and plasminogen activator inhibitor-1) in samples from 80 patients. The results demonstrate that together ST2, ANG2, L-Ficolin, HA, and VCAM1 compose a biomarker panel for diagnosis of SOS. L-Ficolin, HA, and VCAM1 also stratified patients at risk for SOS as early as the day of HCT. Prognostic Bayesian modeling for SOS onset based on L-Ficolin, HA, and VCAM1 levels on the day of HCT and clinical characteristics showed >80% correct prognosis of SOS onset. These biomarkers may provide opportunities for preemptive intervention to minimize SOS incidence and/or severity.
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Affiliation(s)
- Ayman Akil
- Department of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Qing Zhang
- Department of Genomics, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Christen L Mumaw
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana
| | - Nisha Raiker
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana
| | - Jeffrey Yu
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana
| | | | - Laura S Haneline
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana; Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Kent A Robertson
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana
| | - Jodi Skiles
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana
| | | | - Enric Carreras
- Hospital Clinic, IDIBAPS, Barcelona, Spain; José Carreras Foundation & Leukemia Research Institute, Barcelona, Spain
| | - Jamie Renbarger
- Department of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana
| | - Samir Hanash
- Red and Charline McCombs Institute for the Early Detection and Treatment of Cancer, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Robert R Bies
- Department of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Sophie Paczesny
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana.
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Fan CQ, Crawford JM. Sinusoidal obstruction syndrome (hepatic veno-occlusive disease). J Clin Exp Hepatol 2014; 4:332-46. [PMID: 25755580 PMCID: PMC4298625 DOI: 10.1016/j.jceh.2014.10.002] [Citation(s) in RCA: 182] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Accepted: 10/20/2014] [Indexed: 12/12/2022] Open
Abstract
Hepatic sinusoidal obstruction syndrome (SOS) is an obliterative venulitis of the terminal hepatic venules, which in its more severe forms imparts a high risk of mortality. SOS, also known as veno-occlusive disease (VOD), occurs as a result of cytoreductive therapy prior to hematopoietic stem cell transplantation (HSCT), following oxaliplatin-containing adjuvant or neoadjuvant chemotherapy for colorectal carcinoma metastatic to the liver and treated by partial hepatectomy, in patients taking pyrrolizidine alkaloid-containing herbal remedies, and in other particular settings such as the autosomal recessive condition of veno-occlusive disease with immunodeficiency (VODI). A central pathogenic event is toxic destruction of hepatic sinusoidal endothelial cells (SEC), with sloughing and downstream occlusion of terminal hepatic venules. Contributing factors are SEC glutathione depletion, nitric oxide depletion, increased intrahepatic expression of matrix metalloproteinases and vascular endothelial growth factor (VEGF), and activation of clotting factors. The clinical presentation of SOS includes jaundice, development of right upper-quadrant pain and tender hepatomegaly, ascites, and unexplained weight gain. Owing to the potentially critical condition of these patients, transjugular biopsy may be the preferred route for liver biopsy to exclude other potential causes of liver dysfunction and to establish a diagnosis of SOS. Treatment includes rigorous fluid management so as to avoid excessive fluid overload while avoiding too rapid diuresis or pericentesis, potential use of pharmaceutics such as defibrotide, coagulolytic agents, or methylprednisolone, and liver transplantation. Proposed strategies for prevention and prophylaxis include reduced-intensity conditioning radiation for HSCT, treatment with ursodeoxycholic acid, and inclusion of bevacizumab with oxaliplatin-based chemotherapeutic regimes. While significant progress has been made in understanding the pathogenesis of SOS and in mitigating against its adverse outcomes, this condition remains a serious complication of a selective group of medical treatments.
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Key Words
- AML, acute myeloid leukemia
- APRI, aspartate aminotransferase to platelet ratio
- AST, aspartate aminotransferase
- Bmab, bevacizumab
- Colorectal cancer
- DF, defibrotide
- FOLFOX, chemotherapy regimen containing Folinic acid, 5-Fluorouracil, and Oxaliplatin
- GO, gemtuzumab ozogamicin
- GSTM1, glutathione S-transferase M1
- GVHD, graft-versus-host disease
- HSCT, hematopoietic stem cell transplantation
- Hematopoietic stem cell transplantation
- Herbal remedies
- Liver
- MOF, multi-organ failure
- Oxaliplatin
- PML, promyelocytic leukemia protein
- RIC-HSCT, reduced-intensity conditioning hematopoietic stem cell transplantation
- RILD, radiation-induced liver disease
- RT, radiation therapy
- SEC, sinusoidal endothelial cells
- SOS, sinusoidal obstruction syndrome
- TBI, total body irradiation
- TIPS, transjugular intrahepatic porto-systemic shunt
- UPLC-MS, ultra-performance liquid chromatography-mass spectrometry
- V-PYRRO/NO, O(2)-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate
- VEGF, vascular endothelial growth factor
- VEGFR, vascular endothelial growth factor receptor
- VOD, veno-occlusive disease
- VODI, veno-occlusive disease with immunodeficiency
- l-NAME, N(G)-nitro-l-arginine methyl ester
- s-ICAM-1, soluble intercellular adhesion molecular-1
- t-PA, tissue plasminogen activator
- v-WF, von Willebrand factor
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Affiliation(s)
| | - James M. Crawford
- Address for correspondence: James M. Crawford, North Shore-LIJ Laboratories, 10 Nevada Drive, Lake Success, NY 11042-1114, USA. Tel.: +1 516 719 1060; fax: +1 516 719 1062.
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Carreras E. How I manage sinusoidal obstruction syndrome after haematopoietic cell transplantation. Br J Haematol 2014; 168:481-91. [PMID: 25401997 DOI: 10.1111/bjh.13215] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2014] [Accepted: 10/15/2014] [Indexed: 12/24/2022]
Abstract
Sinusoidal obstruction syndrome (SOS), also called veno-occlusive disease of the liver, is one of the most relevant complications of endothelial origin that appears early after haematopoietic cell transplantation (HCT). Despite its relatively low incidence and the fact that most cases of SOS resolve spontaneously, the cases that evolve to multi-organ failure (MOF; severe SOS) have a mortality rate higher than 80% and represent one of the major clinical problems after HCT. For this reason, transplantation teams must have a pre-established policy regarding preventive measures in high-risk patients, strict daily control of weight and fluid balance during HCT, homogeneous diagnostic criteria, appropriate complementary studies for a correct differential diagnosis and measures to prevent and manage hepatorenal syndrome; in addition they must also be ready to start early treatment with defibrotide in patients with a possible severe SOS. Due to the lack of definitive evidence to enable the establishment of general recommendations in the management of SOS, this review analyses all of these aspects based on the author's personal experience.
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Affiliation(s)
- Enric Carreras
- Haematology Department, Hospital Clinic, Barcelona, Spain; Spanish Bone Marrow Donor Program, Josep Carreras Foundation, Barcelona, Spain; Josep Carreras Leukaemia Research Institute, Barcelona, Spain
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