Disclaimer. Similarly, prospective data from the large US expanded-access treatment protocol reported a day +100 OS of 47.1% among 430 adult patients (>16 years), and an overall incidence of hemorrhagic events of 29% [29]. Major complications of HSCT include hepatic veno-occlusive disease (VOD), also known as hepatic sinusoidal obstruction syndrome. 2023 Jan 20;12(3):826. doi: 10.3390/jcm12030826. Only one randomized controlled trial was available. However, this may not be the case in the context of haploidentical allo-HCT with other conditioning regimens incorporating one or more alkylating agents and posttransplant cyclophosphamide. 2002;29:13743. Overall, data are scarce and difficult to interpret, mainly retrospective and single center, with no dose defined. Bookshelf Picod A, Bonnin A, Battipaglia G, Giannotti F, Ruggeri A, Brissot E, et al. Johnson DB, Chandra S, Sosman JA. Feldman L, Gabai E, Milovic V, Jaimovich G. Recombinant tissue plasminogen activator (rTPA) for hepatic veno-occlusive disease after allogeneic BMT in a pediatric patient. It is also uncertain which sub-group of patients is more likely to benefit. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. The third randomized controlled trial again compared ursodeoxycholic acid with no ursodeoxycholic acid[28]. https://doi.org/10.1038/s41409-019-0705-z, DOI: https://doi.org/10.1038/s41409-019-0705-z. 1993;118:25567. En general, los trasplantes autgenos de clulas madre se realizan en personas que necesitan dosis elevadas de quimioterapia y radiacin para curar sus enfermedades. 2019;133:1208. Ruutu T, Eriksson B, Remes K, Juvonen E, Volin L, Remberger M, et al. European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party. INTRODUCTION. This risk score take into account patients age, Karnofsky, sirolimus use, hepatitis B/C status, conditioning regimen, and disease/disease status at time of transplantation (link for calculation https://www.cibmtr.org/ReferenceCenter/Statistical/Tools/Pages/VOD.aspx). Although bleeding is usually not life threatening in patients with hemorrhagic cystitis or severe mucositis, their management may be difficult, and DF discontinuation may be necessary, again depending on the risk/benefit ratio. We therefore recommend against the use of methylprednisolone alone as a prolonged primary treatment of SOS/VOD, especially given the risk of infectious complications associated with high-dose corticosteroids. Blood. We studied the potential role of continuous administration of low-dose heparin for VOD prevention in 234 consecutive patients who underwent ABMT in our institution. (95% CI 7.8-9.4%) in autologous transplant recipients . While these results compare favorably to patients with severe/very severe SOS/VOD, the mortality remains significant, highlighting the importance to treat these patients. 2018;24:9195. Five of 35 patients (14.3%) who received ursodeoxycholic acid compared with 13 of 32 patients (40.6%) who received placebo developed hepatic VOD, which was significantly different (RR 0.35, 95% CI: 0.14-0.88, P = 0.02). Cheuk DK, Wang P, Lee TL, Chiang AK, Ha SY, Lau YL, Chan GC. Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin lymphoma. CAS Prophylactic defibrotide in allogeneic stem cell transplantation: minimal morbidity and zero mortality from veno-occlusive disease. There are many risks associated with this treatment, and it can take several months to recover. Keywords: Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease after Autologous Ursodiol prophylaxis against hepatic complications of allogeneic bone marrow transplantation. 2000;64:3238. The drug should be administered at the same dose as in the therapeutic setting (25mg/kg per day divided in four daily doses of 6.25mg/kg). Cappelli B, Chiesa R, Evangelio C, Biffi A, Roccia T, Frugnoli I, Biral E, No A, Fossati M, Finizio V, et al. Our transplant program is accredited by the Foundation for the Accreditation of Cellular Therapy, the standard of excellence for blood and bone marrow transplant programs in the United States. Sakaguchi H, Watanabe N, Muramatsu H, Doisaki S, Yoshida N, Matsumoto K, Kato K. Danaparoid as the prophylaxis for hepatic veno-occlusive disease after allogeneic hematopoietic stem cell transplantation in childhood hematological malignancy. Dalle JH, Giralt SA. Epub 2013 Sep 17. Google Scholar. PubMed For patients with life-threatening bleeding, DF must be immediately discontinued, and its resumption should be discussed on a case per case basis and according to the risk/benefit ratio. PubMed Central Richardson PG, Corbacioglu S, Ho VT, Kernan NA, Lehmann L, Maguire C, et al. Biol Blood Marrow Transplant. Osteochondral allograft transplantation uses a graft from a donor to transplant healthy cartilage tissue to the damaged area and is preferred for larger defects. Yu X, Liu L, Xie Z, Dong C, Zhao L, Zhang J, et al. Specific therapeutic options on top of these include tissue plasminogen activator[33-44], heparin[36], thrombomodulin[45], antithrombin III[46-49], protein C[50], prostaglandin E1[51], glutamine[52,53], acetylcysteine[54], methylprednisolone[55], and defibrotide[56-63]. Antithrombin-III for the treatment of chemotherapy-induced organ dysfunction following bone marrow transplantation. Introduction. Veno-Occlusive Disease of the Liver after High-Dose Cytoreductive Successful treatment of hepatic veno-occlusive disease after myeloablative allogeneic hematopoietic stem cell transplantation by early administration of a short course of methylprednisolone. Epub 2019 Feb 22. The site is secure. Veno-occlusive disease (VOD) of the liver in Korean patients following allogeneic bone marrow transplantation (BMT): efficacy of recombinant human tissue plasminogen activator (rt-PA) treatment. Kallianpur AR, Hall LD, Yadav M, Byrne DW, Speroff T, Dittus RS, Haines JL, Christman BW, Summar ML. Because of its high incidence and mortality, prophylaxis for hepatic VOD is widely practiced, using different regimens in different centers. However, the combined results of the three prospective clinical trials using ursodeoxycholic acid alone as prophylaxis vs. no treatment demonstrated a reduced proportion of SOS (relative risk, 0.34; 95% confidence interval, 0.170.66) [49]. Bordigoni P, Witz F, Von Bueltzingsloewen A, Schmitt C, Sommelet D. Prostaglandin E1 (PGE1) induced arthritis following bone marrow transplantation. In adult patients, Baltimore criteria have been reported to be more specific than the Seattle one for SOS/VOD diagnosis: specifically, while hemodynamic studies could not confirm the diagnosis in 42% of patients assessed by the Seattle criteria, such lack of confirmation was seen in only 9% of patients using the Baltimore criteria, a finding further validated by corroboration with histopathology [8, 9]. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in It may be autologous (the patient's own stem cells are used), allogeneic (the stem cells come from a donor) or syngeneic . Introduction: Autologous hematopoietic stem cell transplant is an important treatment modality used to achieve long-term remission in people with multiple myeloma. Treatment with DF was associated with a significantly higher CR rate (24 vs. 9%, p=0.013) and day +100 OS (38 vs. 25%, p=0.034). In contrast, the second trial comparing low dose heparin infusion (100 units/kg per day from Day-8 to Day+30) with no heparin in both allogeneic and autologous HSCT recipients showed a significantly lower incidence of VOD in the heparin group[30]. We retrospectively reviewed data of pediatric HSCTs performed in 13 AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica)-affiliated centers between January 2000 and April 2016. There was one double-blind randomized controlled trial assessing the efficacy of enoxaparin for prevention of hepatic VOD in allogeneic and autologous bone marrow transplant recipients above 15 years of age[31]. Attal M, Huguet F, Rubie H, Charlet JP, Schlaifer D, Huynh A, et al. World J Clin Cases. Epub 2021 Jul 13. Bearman SI, Lee JL, Barn AE, McDonald GB. Veno-occlusive disease of the liver after busulfan, melphalan, and thiotepa conditioning therapy: incidence, risk factors, and outcome. Park M, Park HJ, Eom HS, Kwon YJ, Park JA, Lim YJ, et al. 1991;78:1389. It is also unclear who should receive prophylaxis and which treatment is most likely to offer the best risk-benefit ratio. Helmy A. Am J Hematol. Therefore, the use of ursodeoxycholic acid is recommended from the beginning of the conditioning until day 90 after transplantation. Br J Haematol. The incidence of hepatic VOD was not reported in this study. BCSH/BSBMT guideline: diagnosis and management of venoocclusive Carreras E, Diaz-Ricart M. The role of the endothelium in the short-term complications of hematopoietic SCT. 2007;13:20617. HSCT: Hematopoietic stem cell transplantation. There was also no significant difference in the frequency of severe VOD (2.4% vs 6.0%, RR 0.40, 95% CI: 0.08-2.03, P = 0.27). Hepatic Veno-occlusive Disease (Sinusoidal Obstruction Syndrome) After Despite the incidence of SOS/VOD being limited, around 1015% after myeloablative allo-HCT and up to 5% after reduced-intensity conditioning (RIC) allo-HCT, particular attention must be paid to permit its early detection and treatment and to prevent the development of the most severe forms, which are in turn associated with a very high mortality rate (>80%) [1, 5]. Prophylactic, preemptive, and curative treatment for sinusoidal Retrospective multivariate analysis of hepatic veno-occlusive disease after blood or marrow transplantation: possible beneficial use of low molecular weight heparin. 1998;128:97581. Li QP, Zhu WG, Yin XJ, Feng ZC. Bone Marrow Transpl. Yakushijin K, Atsuta Y, Doki N, Yokota A, Kanamori H, Miyamoto T, et al. Ruutu T, Eriksson B, Remes K, Juvonen E, Volin L, Remberger M, Parkkali T, Hgglund H, Ringdn O. Ursodeoxycholic acid for the prevention of hepatic complications in allogeneic stem cell transplantation. Dignan F, Gujral D, Ethell M, Evans S, Treleaven J, Morgan G, et al. Limitations of these treatment modalities include access-related difficulty, cost, creation of a secondary donor site, use of singular or limited cell types, and sparse or contradictory evidence basis of their efficacy of use. It has been linked to conditioning regimens preceding hematopoietic cell transplant (HCT) but little is known about its epidemiology and characteristics outside the HCT setting. There was one double-blind randomized controlled trial that compared glutamine with isonitrogenous amino acid mixture for protection of hepatic function in allogeneic or autologous bone marrow transplant recipients[19]. Most commonly used diagnostic criteria for VOD includes the Seattle criteria[2], the modified Seattle criteria[3], and the Baltimore criteria (also called Jones criteria)[4]. Anscher MS, Peters WP, Reisenbichler H, Petros WP, Jirtle RL. Al Beihany A, Al Omar H, Sahovic E, Chaudhri N, Al Mohareb F, Al Sharif F, Al Zahrani H, Al Shanqeeti A, Seth P, Zaidi S, et al. Elementary measures such as comfortable positioning, appropriate reassurance, and psychological support are also an important part in supportive care as well as during treatment. Veno-occlusive disease (VOD) is a major cause of toxic death after autologous bone marrow transplantation (ABMT). CAS Lee JL, Gooley T, Bensinger W, Schiffman K, McDonald GB. Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD), is a potentially life-threatening complication that may develop after hematopoietic stem cell transplantation (HSCT). Practice guidelines from this initiative for each particular question forms the basis of this article and lays out a roadmap of common issues encountered with prophylactic, preemptive, and curative treatment for SOS/VOD in adult patients with reference to the commercially available products and on clinical trials. Early diagnostic value of liver stiffness measurement in hepatic sinusoidal obstruction syndrome induced by hematopoietic stem cell transplantation. Wadleigh M, Richardson PG, Zahrieh D, Lee SJ, Cutler C, Ho V, Alyea EP, Antin JH, Stone RM, Soiffer RJ, et al. CAS Provided by the Springer Nature SharedIt content-sharing initiative, Journal of Cancer Research and Clinical Oncology (2023), Bone Marrow Transplantation (Bone Marrow Transplant) Distinct deleterious effects of cyclosporine and tacrolimus and combined tacrolimus-sirolimus on endothelial cells: protective effect of defibrotide. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Co-transplantation of autologous Treg cells in a cell therapy for Goringe AP, Brown S, O'Callaghan U, Rees J, Jebb S, Elia M, Poynton CH. Diagnosis of hepatic VOD is based on a constellation of symptoms and signs and serum bilirubin level. 2012;379:13019. Treatment of severe veno-occlusive disease with defibrotide: compassionate use results in response without significant toxicity in a high-risk population. Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD), is a potentially life-threatening complication that can develop after hematopoietic stem cell transplantation (HSCT). Skip to content Care at Mayo Clinic Care at Mayo Clinic About Mayo Clinic The incidence of hepatic VOD after HSCT varies from 0 to 77%, depending on the risk of the patient cohort; and the median incidence is 13.3% [ 1 ]. Late-onset hepatic veno-occlusive disease post autologous The overall mortality directly related to SOS/VOD was 15.5%. 2002;100:197783. The difference was not statistically significant (RR 0.13, 95% CI: 0.01-2.28, P = 0.16). Incidence and risk factors of hepatic veno-occlusive disease - Nature Eighteen patients received daily infusion of 50 g glutamine and 16 patients received daily infusion of isonitrogenous amino acid mixture. Marsa-Vila L, Gorin NC, Laporte JP, Labopin M, Dupuy-Montbrun MC, Fouillard L, Isnard F, Najman A. Prophylactic heparin does not prevent liver veno-occlusive disease following autologous bone marrow transplantation. Hasegawa S, Horibe K, Kawabe T, Kato K, Kojima S, Matsuyama T, Hirabayashi N. Veno-occlusive disease of the liver after allogeneic bone marrow transplantation in children with hematologic malignancies: incidence, onset time and risk factors. The .gov means its official. Clinical signs and symptoms of SOS/VOD include weight gain, ascites, symptomatic hepatomegaly and hyperbilirubineamia [1], [2], [3]. Ursodeoxycholic acid for SOS/VOD prevention has been evaluated in several prospective randomized trials. Mashegu H, Smith L, Li Y, Seif A, Grupp S, Bunin N. The role of peritoneal drainage in veno-occlusive disease in pediatric patients post hematopoietic stem cell transplant. and transmitted securely. Ann Intern Med. The current trend is to transfuse blood components . Patients allocated to the FFP group (23 patients) received twice weekly FFP infusions from the start of conditioning till Day+28 after HSCT and patients in the control group (20 patients) did not receive FFP. Hepatic veno-occlusive disease, also known as sinusoidal obstruction syndrome (VOD/SOS), is a life-threatening complication after both autologous and allogeneic hematopoietic stem cell transplantation (HSCT) 1, 2, 3.Diagnosis of VOD/SOS is based on clinical and analytical criteria, using the Baltimore criteria, modified Seattle criteria, and, more recently, the European Society . Prevention of regimen-related toxicities after bone marrow transplantation by pentoxifylline: a prospective, randomized trial. Bone marrow versus peripheral blood as a graft source for haploidentical donor transplantation in adults using post-transplant cyclophosphamide-A systematic review and meta-analysis. In patients with only one major and/or multiple minor risk factors, there is no literature supporting the use of DF for SOS/VOD prophylaxis. Some of the above have also been tried in combination[36,51,64-66]. Haematologica. Clipboard, Search History, and several other advanced features are temporarily unavailable. Patients with severe MOD and MOF are generally transferred to an intensive care unit. Fifty-eight percent of patients were alive at day +100 post allo-HCT. 2004;10:34754. The recommended duration of DF treatment is at least 21 days, and until resolution of all SOS/VOD symptoms. This work was made possible thanks to the support of the Association for Training, Education, Research, in Hematology, Immunology and Transplantation (ATHERIT), which received an unrestricted educational grant from JAZZ pharmaceuticals. Higashigawa M, Watanabe M, Nishihara H, Tabata N, Azuma E, Ido M, Ito M, Sakurai M. Successful treatment of an infant with veno-occlusive disease developed after allogeneic bone marrow transplantation by tissue plasminogen activator, heparin and prostaglandin E1. PubMedGoogle Scholar. Ann Transplant. Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life-threatening complication that can develop after hematopoietic cell transplantation. Details. sharing sensitive information, make sure youre on a federal Outside this work, all authors received honoraria and/or research support from JAZZ Pharmaceuticals whose product is discussed in this manuscript, but JAZZ pharmaceuticals did not participate to the discussions, conduct of the work, data/results analyses, or manuscript writing or reviewing. However, the duration of hyperbilirubinemia and hepatomegaly appeared shorter in the enoxaparin group compared to the control group (mean 7.4 d vs 15.3 d, P = 0.008; and mean 2.4 d vs 5.5 d, P = 0.03, respectively). Hepatitis C virus as a risk factor for the development of veno-occlusive disease of the liver. Toksvang LN, De Pietri S, Nielsen SN, Nersting J, Albertsen BK, Wehner PS, et al. Recombinant tissue plasminogen activator (rt-PA) for veno-occlusive liver disease in pediatric autologous bone marrow transplant patients. Dignan FL, Wynn RF, Hadzic N, Karani J, Quaglia A, Pagliuca A, Veys P, Potter MN; Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. Therefore, a historical control group (n=32) was used in this trial. The conditioning regimen and immune-mediated injury following allogeneic HCT (allo-HCT) generate toxic metabolites that damage sinusoidal endothelial cells. The aims of this retrospective multicenter study were to evaluate the incidence of SOS/VOD in a lar However, hyperbilirubinemia and jaundice are almost invariably present in classic SOS/VOD in adult patients [8]. Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS) is a rare complication characterized by hepatomegaly, right-upper quadrant pain, jaundice, and ascites, occurring after high-dose chemotherapy, hematopoietic stem cell transplantation (HSCT) and, less commonly, other conditions. The dose of 25mg/kg/day is well established. Morris JD, Harris RE, Hashmi R, Sambrano JE, Gruppo RA, Becker AT, Morris CL. 2022 Oct;42(7):1535-1544. doi: 10.1007/s10875-022-01305-6. Veno-occlusive disease of the liver in children with solid tumors Key Definitions Autologous transplantation: patients receive their own stem cells after a course of myeloablative conditioning; about 12,000 are performed each year. Since different studies on prophylaxis and treatment of hepatic VOD might have used different criteria for diagnosis of VOD, comparisons of effectiveness of prophylaxis and treatment regimens across different studies may be difficult. Internet Explorer). Overall, the use of doses over 25mg/kg/day seems to be associated with more toxicity without any clinical benefit, while lower doses are less effective. Goldberg SL, Shubert J, Rao AK, Redei I, Klumpp TR, Mangan KF. In contrast, beyond day 21, hyperbilirubinemia is less consistent [8, 11, 12]. This multicenter open-label randomized controlled trial compared defibrotide at 25 mg/kg per day (arm A, 76 patients) with 40 mg/kg per day (arm B, 75 patients), both divided into 4 daily doses, given for at least 2 wk or until complete response[74]. For example, the high incidence of SOS/VOD associated with inotuzumab raises the question of SOS/VOD careful monitoring in this setting, in particular as to the role of DF prophylaxis. Richardson PG, Murakami C, Jin Z, Warren D, Momtaz P, Hoppensteadt D, Elias AD, Antin JH, Soiffer R, Spitzer T, et al. FOIA Prophylactic fresh frozen plasma may prevent development of hepatic VOD after stem cell transplantation via ADAMTS13-mediated restoration of von Willebrand factor plasma levels. Yakushijin K, Matsui T, Okamura A, Yamamoto K, Ito M, Chihara K. Successful treatment with defibrotide for sinusoidal obstruction syndrome after hematopoietic stem cell transplantation. Google Scholar. Al Beihany A, Al Omar H, Sahovic E, Chaudhri N, Al Mohareb F, Al Sharif F, et al. An allogeneic transplant uses stem cells from a donor whose human leukocyte antigens (HLA) are acceptable matches to the patient's. Similar to trials on ursodeoxycholic acid, both trials on heparin prophylaxis failed to show survival benefit. Although various treatment options for hepatic VOD are available, most have not undergone stringent evaluation with randomized controlled trial and therefore it remains uncertain which treatment offers real benefit. N Engl J Med. Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure: response without significant toxicity in a high-risk population and factors predictive of outcome. In an effort to improve early diagnosis, the European Group for Blood and Marrow Transplantation (EBMT) revise the modified Seattle [6] and Baltimore [4] criteria, and recently published revised diagnosis and severity criteria for adults [7]. DF should be resumed at the same dose, and as clinically indicated, hepatic biopsy is recommended to rule out confounding alternate the diagnoses. Nonrelapse mortality was significantly higher 1 and 5 years after transplantation in patients who developed SOS/VOD (P < .001). Four of the 52 patients (7.7%) in the heparin group developed hepatic VOD and 1 of the 46 patients (2.2%) in the control group had hepatic VOD (RR 3.54, 95% CI: 0.41-30.53, P = 0.25). Only 2 of 81 patients (2.5%) in the treatment group developed hepatic VOD, which was significantly less frequent compared to the control group, in which VOD occurred in 11 of 80 patients (13.7%) (RR 0.18, 95% CI: 0.04-0.78, P = 0.02). Please enable it to take advantage of the complete set of features! Fssiov M, vec P, Horkov J, Sedlek P, Roho P, Celec P, Boov I, Adamkov J, Skora T, Dobinsk V, Pozdechov M, Dczyov D, Vargov S, Kolenov A. J Clin Med. Chopra R, Eaton JD, Grassi A, Potter M, Shaw B, Salat C, Neumeister P, Finazzi G, Iacobelli M, Bowyer K, et al. The site is secure. Blood. The mortality of severe VOD is high at average of 84%[1]. Hepatic veno-occlusive disease (VOD) remains one of the commonest and most serious complications after myeloablative hematopoietic stem cell transplantation (HSCT). In some cases, charcoal hemofiltration[67], transjugular intrahepatic portosystemic shunt[68-71] or liver transplantation is performed as last resort[72,73]. government site. Rosti G, Bandini G, Belardinelli A, Calori E, Tura S, Gherlinzoni F, Miggiano C. Alteplase for hepatic veno-occlusive disease after bone-marrow transplantation. Cutler C, Stevenson K, Kim HT, Richardson P, Ho VT, Linden E, Revta C, Ebert R, Warren D, Choi S, et al. PRIMARY OBJECTIVE: To evaluate the ability of ibrutinib to improve 24-month progression free survival (PFS . Blood. FOIA In particular, whenever possible, antifungal azoles should be substituted for echinocandin. Expert Opin Drug Saf. Treatment of hepatic veno-occlusive disease with low-dose tissue plasminogen activator: impact on coagulation profile. One patient in the control group died from sepsis and acute graft-vs-host disease, while all patients in the glutamine group survived. Although its precise mechanism of action in SOS/VOD remains an area of active investigation, it involves two distinct elements: the protection of endothelial cells and restoration of the thrombotic-fibrinolytic balance [1]. Therefore, hyperbilirubinemia is not mandatory for the diagnosis of late SOS/VOD, provided patients present with at least two other clinical manifestations (painful hepatomegaly, weight gain >5%, and/or ascites) as well as hemodynamic and/or ultrasound evidence of SOS/VOD. Furthermore, hepatotoxic drugs should be discontinued whenever possible [1]. All authors designed the manuscript, analyzed the literature, and wrote and commented on the manuscript. Careers. Therefore, careful surveillance may allow early detection of SOS/VOD, particularly as the licensed available drug is proven to be effective and reduce mortality. Batsis I, Yannaki E, Kaloyannidis P, Sakellari I, Smias C, Georgoulis I, Fassas A, Anagnostopoulos A. Veno-occlusive disease prophylaxis with fresh frozen plasma and heparin in bone marrow transplantation. Horn B, Reiss U, Matthay K, McMillan A, Cowan M. Veno-occlusive disease of the liver in children with solid tumors undergoing autologous hematopoietic progenitor cell transplantation: a high incidence in patients with neuroblastoma. A multiagent strategy to decrease regimen-related toxicity in children undergoing allogeneic hematopoietic stem cell transplantation. Treatment of hepatic venocclusive disease with recombinant human tissue plasminogen activator and heparin in 42 marrow transplant patients. Herbaux C, Gauthier J, Brice P, Drumez E, Ysebaert L, Doyen H, et al. A randomized controlled trial of pentoxifylline for the prevention of regimen-related toxicities in patients undergoing allogeneic marrow transplantation. The decision of whether to have a stem cell transplant . There were 2 open-label randomized controlled trials evaluating heparin for hepatic VOD prophylaxis. Bulley SR, Strahm B, Doyle J, Dupuis LL. One open-label randomized controlled trial compared FFP infusion with no FFP for prophylaxis of hepatic VOD in allogeneic HSCT recipients[32]. Transjugular intrahepatic portosystemic shunt after adult liver transplantation: experience in eight patients. Richardson PG, Riches ML, Kernan NA, Brochstein JA, Mineishi S, Termuhlen AM, et al. Autologous vs. Allogenic Stem Cell Transplants: What's the Difference?