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1.
Prophylactic use of defibrotide (DF) to prevent veno‐occlusive disease (VOD), a relatively common and high‐risk complication of hematopoietic stem cell transplantation (HSCT), may be an encouraging modality to reduce morbidity and mortality from VOD. However, conclusions remain unclear. We carried out a systematic review to summarize the state of knowledge. One randomized controlled trial (RCT), four cohort studies and eight case series studies were found, including a total of 1230 patients. The overall mean incidence of VOD in patients using DF was 4.7% (95% CI, 3.3–6.1) which was significantly lower than the data 13.7% (95% CI, 13.3–14.1) across 135 studies using no VOD prophylaxis (p < 0.005). The meta‐analysis of the incidence of VOD in controlled trials revealed a statistical reduction in VOD incidence in the DF group (RR = 0.47, 95% CI, 0.31–0.73). The overall mean incidence of severe VOD was 0.8% (95% CI, 0.2–1.4). The RR was 0.31 (95% CI, 0.09–1.06). However, the lack of RCTs and the methodological weaknesses of the studies may preclude making generalizable conclusions. Our review described that DF appears promising for VOD prevention and large RCT is needed for further confirmation. 相似文献
2.
Teisseyre M Teisseyre J Kalicinski P Wolska-Kusnierz B Ismail H Bernatowska E Markiewicz-Kijewska M Ostoja-Chyzynska A Jankowska I Kluge P Pawlowska J Szymczak M 《Transplantation proceedings》2010,42(10):4608-4610
Chronic graft-versus-host disease (GVHD) is a frequent complication of bone marrow transplantation (BMT). After the skin, the liver is the second, most frequent target of GVHD, which presenting with hyperbilirubinemia, elevated liver enzymes, and coagulopathy. Progressive destruction of small intrahepatic bile ducts causes vanishing bile duct syndrome and leads to end-stage liver disease. We report 2 successful cases of orthotopic liver transplantation performed in children with severe GVHD after hematopoietic stem cell transplantation from a matched unrelated donor (HSCT-MUD). 相似文献
3.
X Troussard J F Bernaudin C Cordonnier J Fleury D Payen J Briere J P Vernant 《Thorax》1984,39(12):956-957
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5.
Nakazawa Y Chisuwa H Mita A Ikegami T Hashikura Y Terada M Nakayama J Kawasaki S 《Transplantation》2003,75(5):727-730
Veno-occlusive disease (VOD) can develop in association with the administration of cytotoxic chemotherapeutic agents and irradiation. In solid-organ transplant settings, azathioprine has been implicated as a predisposing factor. VOD with fatal outcome occurred in a post liver-transplant recipient who had never been exposed to any agents that have the potential to induce VOD. At onset, the disease manifested clinically as gross ascites and progressive jaundice and was observed after clinically diagnosed acute graft rejection. The disease was confirmed by histologic examinations. Histologic studies of biopsy samples from this patient revealed that most small hepatic veins less than 300 microm in diameter were affected, exhibiting concentric intimal thickening with sparse inflammatory cells. A few of the hepatic veins exhibited active endotheliitis with occasional extension of inflammation to neighboring centrilobular areas. Despite intensified immunosuppression, the observed fibrous obliterative changes were irreversible. Although the cause of VOD in this patient is tentative, the damage to the endothelium, associated with acute rejection, is likely to be attributable. VOD deserves recognition as one of the causes for liver dysfunction and persistent ascites after liver transplantation. 相似文献
6.
Levels of anti-A/B antibodies after ABO-incompatible hematopoietic stem cell transplantation 总被引:1,自引:0,他引:1
In contrast to solid organ transplantation, ABO incompatibility is generally not associated with survival differences in hematopoietic stem cell transplantation. Therefore, patients receiving ABO-incompatible stem cell transplantation can be analyzed to study the mechanism of tolerance induction after antigen-mismatched transplantation. The goal of this study was to analyze the levels of anti-A/B antibodies after ABO-incompatible transplantation. Host-derived antidonor antibodies disappeared rapidly after transplantation and did not reappear in the further posttransplant course. Donor-derived antihost antibodies did not significantly increase and compatible anti-A/B antibodies remained positive after hematopoietic stem cell transplantation. Thus, there is no evidence for stimulation of donor B lymphocytes to produce antirecipient antibodies suggesting a potential B cell tolerance. 相似文献
7.
ABO-incompatible living-donor kidney transplantation in children 总被引:8,自引:0,他引:8
Shishido S Asanuma H Tajima E Hoshinaga K Ogawa O Hasegawa A Honda M Nakai H 《Transplantation》2001,72(6):1037-1042
BACKGROUND: Due to a severe shortage of suitable cadaveric allografts for children awaiting kidney transplants, we have performed a series of ABO-incompatible living kidney transplantations (LKT) at our institution. METHODS: Between July 1989 and March 2000, 16 pediatric patients (3 female, 13 male) underwent ABO-incompatible LKT. The mean age at transplantation was 10.9+/-4.3 years (range 5.1-15.0 years). The donor to recipient ABO blood antigen incompatibility was as follows: A1-->O, 5 patients; B-->O, 6 patients; A1B-->B, 2 patients; and A1B -->B, A1-->B, or B-->A1, 1 patient each. The median pretransplantation anti-A1 titers of eight A-incompatible recipients were 1:128 (IgM, range 1:16 to 1:512) and 1:32 (IgG, range 1:2 to 1:128). Median anti-B titers of seven B-incompatible recipients were 1:32 (IgM, range 1:4 to 1:128) and 1:8 (IgG, range 1:2 to 1:64). All patients received three or four sessions of plasmapheresis (PP) and/or immunoadsorption (IA) to remove the anti-A and/or anti-B antibodies before transplantation. Immunosuppression initially consisted of cyclosporine, methylprednisolone, cyclophosphamide, and antilymphocyte globulin. Splenectomy was performed on all recipients at the time of transplantation. RESULTS: The patients were followed for 6 to 122 months with a mean follow-up of 63 months. All 16 recipients who underwent ABO-incompatible LKT achieved a pretransplant isoagglutinin titer less than 1:8 with 3-4 sessions of PP/IA treatment. Of 16 patients, 10 patients had rebound increase in their IgM and/or IgG anti-A/B titers to greater than 1:64 or predepletion levels within 10 days posttransplantation. In addition, nine patients developed renal dysfunction in association with the rebound increase in their anti-A/B. One patient lost his graft because of uncontrolled delayed hyperacute rejection, whereas eight other recipients recovered completely with pulse steroids and PP/IA therapy. After the third week posttransplant, there was no correlation between the occurrence of AR and their isoagglutinin titers. Moreover, no antibody-mediated rejection was observed, even in recipients with continued high titer anti-A and/or anti-B antibodies. Patient survival is 100% to date. The actuarial 1-year and 5-year graft survival rates are 87% and 85%, respectively. No fatal infectious complications occurred despite the combination of splenectomy and immunosuppressive drugs. CONCLUSIONS: We have demonstrated that with adequate pre- and posttransplant management, successful kidney transplantation across the ABO barrier is possible in the pediatric population. "Accommodation" of the allografts occurred within 2 weeks of transplantation. Subsequently, the long-term graft outcome of ABO-incompatible LKT was comparable to that of ABO-compatible LKT. 相似文献
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Gabriel Izbicki David Shitrit Itzhak Schechtman Danielle Bendayan Gershon Fink Gideon Sahar Milton Saute Tuvia Ben-Gal Mordechai R Kramer 《The Journal of heart and lung transplantation》2005,24(5):635-637
Pulmonary veno-occlusive disease, a rare cause of pulmonary hypertension, is characterized by extensive and diffuse occlusion of pulmonary veins by fibrous tissue. Although the diagnosis can be suspected by the presence of the classic clinical triad of severe pulmonary arterial hypertension, radiographic evidence of pulmonary hypertension and edema, and normal pulmonary artery occlusion pressure, the definitive diagnosis is histopathologic. The prognosis of pulmonary veno-occlusive disease is poor with most described patients dying within 2 years of diagnosis. Although anti-coagulation, oxygen, and vasodilator therapies are effective temporarily, the definitive treatment is lung transplantation. We describe the recurrence of pulmonary veno-occlusive disease at 3 months after heart-lung transplantation in a 26-year-old man. Recurrence after transplantation for this disease has not been reported previously, and lung transplantation was thought to be definitive treatment. With this 1st report of early recurrence of pulmonary veno-occlusive disease after heart-lung transplantation, we believe that extrapulmonary factors may play a role in the pathogenesis of this rare disease. 相似文献
9.
Mor E Pappo O Bar-Nathan N Shaharabani E Shapira Z Tur-Kaspa R Ben-Ari Z 《Transplantation》2001,72(7):1237-1240
BACKGROUND: Veno-occlusive disease (VOD) after liver transplantation is associated with acute rejection and poor outcome. The use of antithrombotic and thrombolytic agents is limited by their toxicity. Defibrotide is a polydeoxyribonucleotide with thrombolytic and antithrombotic properties and no systemic anticoagulant effect. METHODS: Defibrotide, 35-40 mg/kg/day, was administered intravenously for 21 days on a compassionate-use basis to two patients aged 66 and 49 years. VOD had developed 6 weeks and 4 months after orthotopic liver transplantation for hepatitis C and hepatitis B infection, respectively. VOD was diagnosed clinically by findings of weight gain (8.5% and 16%), ascites, jaundice (serum bilirubin 5.4 mg/dl and 21.7 mg/dl), and severe coagulopathy (in one patient), and histologically by the presence of hemorrhagic centrilobular necrosis and fibrous stenosis of the hepatic venules. One of the patients had received azathioprine as part of the immunosuppressive regimen. There was no evidence of acute cellular rejection histologically. RESULTS: After 3 weeks of defibrotide administration, the first patient showed complete clinical resolution of the VOD, and serum bilirubin level normalized. He is alive 6 months after transplantation. The second patient, treated at a later stage of disease, showed marked improvement in the coagulopathic state, but there was no resolution of the VOD. He died 2 months later of multiorgan failure due to Escherichia coli sepsis. Neither patient had side effects from the drug. CONCLUSIONS: Defibrotide is a promising drug for the treatment of VOD after liver transplantation and needs to be evaluated in large, prospective studies. 相似文献
10.
《Transplantation reviews (Orlando, Fla.)》2015,29(1):8-15
Liver-related complications constitute a large component of the overall morbidity and mortality associated with hematopoietic cell transplantation. Affecting up to 80% of allogeneic HCT recipients, prompt recognition and treatment are essential. The differential diagnosis is broad and is best categorized by time of onset after transplantation. Early complications include drug-induced liver injury, sinusoidal obstruction syndrome, and graft-versus-host disease. Late complications include infectious sequelae, cirrhosis, and hepatic malignancies. Patients being considered for hematopoietic cell transplantation should be screened and evaluated for liver-related complications to help improve outcomes. 相似文献
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Takehiko Mori Takayuki Shimizu Rie Yamazaki Tomonori Nakazato Yasuo Ikeda Shincihiro Okamoto 《Transplant international》2005,18(10):1215-1217
Tacrolimus is widely used for the prophylaxis and treatment of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (HSCT) and graft rejection in solid organ transplantation. The metabolism of tacrolimus has been reported to be impaired in association with liver dysfunction, mostly as documented in liver transplant recipients. Hepatic veno-occlusive disease (VOD) is one of the serious complications after allogeneic HSCT. It is characterized by jaundice, fluid retention, and painful hepatomegaly, caused by endothelial cell injury resulting from the toxicity of the conditioning regimen. The impaired metabolism of tacrolimus in hepatic VOD has not previously been reported in the literature. Here, we report the notable alteration in the metabolism of tacrolimus in two patients with hepatic VOD, in whom the half-lives of tacrolimus were markedly prolonged (288 and 146 h). 相似文献
13.
Lassau N Auperin A Leclere J Bennaceur A Valteau-Couanet D Hartmann O 《Transplantation》2002,74(1):60-66
BACKGROUND: Currently, the severity of veno-occlusive disease (VOD) is graded retrospectively on the basis of the evolution of clinical and biological criteria. The objective of this study was to describe a noninvasive method capable of predicting the severity of this disease at the time of the diagnosis. METHODS: Seventy-one children who developed VOD after intensive myeloablative therapy with busulfan before hematopoietic stem cell transplantation were included in this study. Sixty-four patients underwent baseline ultrasonography (US) and Doppler examination before transplantation. All patients had posttransplantation US and Doppler examinations at the time of the clinical and biological diagnosis of VOD. Seven US morphological criteria and seven Doppler criteria were studied that yielded three individual scores: a US score, a Doppler score, and a total Doppler ultrasonography (DUS) score. RESULTS: In the univariate analysis, three of 7 US criteria, three of 7 Doppler criteria, and the three scores were correlated with the severity of VOD after transplantation and at the time of the diagnosis. In the multivariate analysis, two US criteria (splenomegaly and ascites) and one Doppler criterion (flow recorded in para-umbilical vein) were correlated with the severity of VOD. The multivariate analysis of the pooled US and Doppler criteria showed that the flow recorded in the para-umbilical vein was the only criterion significantly associated with the grade of VOD (P=0.0001). All patients with a US-Doppler score >9 developed grade 2 or 3 VOD. CONCLUSION: Postgraft US and Doppler examinations have a prognostic significance according to the grade of VOD. 相似文献
14.
Lucia Ortega-Laureano Teresa Santiago Gabriela Maron Andrew M. Davidoff Israel Fernandez-Pineda 《Journal of pediatric surgery》2018,53(6):1129-1133
Background/Purpose
Pulmonary complications are some of the leading causes of morbidity and mortality in immunocompromised pediatric patients. We sought to assess the value of surgical lung biopsy (SLB) in hematopoietic cell transplantation (HCT) pediatric patients.Methods
A retrospective review of patients who underwent SLB within one year of HCT between 1999 and 2015 was performed.Results
Twenty-nine patients (15 females, 14 males) with a median age of 10 years (range, 0.6–23) were identified. Median interval between HCT and SLB was 114.8 days (range, 16–302). At surgery, 11 (38%) patients were intubated, and 7 (24%) were receiving supplemental oxygen. The most common histological finding was cryptogenic organizing pneumonia in 8 cases (27%), followed by infection in 7 (24%). Perioperative complications (17%) included bronchopleural fistula (n = 2), splenic laceration from a trocar injury (n = 2), and hemothorax (n = 1). Changes in therapy occurred in 25 patients (86%). Twenty-four (83%) patients survived more than 30 days post SLB, and the overall survival rate was 41% with a median follow-up of 8.5 years (range, 1–13).Conclusion
SLB appears to be safe and informative in pediatric patients after HCT and led to changes in therapy in most patients. However, long-term survival after this procedure was < 50%, reinforcing the fact that pulmonary complications are some of the leading causes of mortality in these patients.Type of Study
Retrospective analysis.Level of Evidence
Level IV. 相似文献15.
Anders Öberg Margareta Genberg Andrei Malinovschi Hans Hedenström Per Frisk 《American journal of transplantation》2018,18(2):417-423
A symptom‐limited incremental cycle ergometer test was performed in 17 young adult patients treated with hematopoietic cell transplantation and total body irradiation for hematologic malignancies during childhood. These 17 young adult patients were compared with 17 sex‐ and age‐matched healthy control subjects. Assessments of pulmonary function, cardiac function, body composition, and levels of growth hormone were made. The median follow‐up was 17.7 years. Patients achieved 63.2% of the predicted peak workload, whereas controls achieved 96.1% (P < .001). All patients, but only 1 control, failed to achieve a peak workload >80% (P < .001). Fat‐free mass was significantly lower (43.5 vs 57.6 kg, P < .001) and fat mass percentage was significantly higher (31.8% vs 24.2%, P = .011) in the patients. The peak workload adjusted for fat‐free mass was significantly lower in the patients (3.3 vs 4.3, P < .001). In the patients, peak workload correlated significantly with total lung capacity (r = .54, P = .025). In summary, long‐term survivors have significantly decreased exercise capacity compared with healthy individuals. Together with their altered body composition, this may predispose them to cardiovascular disease. 相似文献
16.
BackgroundThe association between vitamin D and acute graft-versus-host disease (GvHD) remains controversial, especially for patients receiving myeloablative conditioning.MethodsWe measured pre-transplantation plasma vitamin D (25-hydroxyvitamin D3 + D2) levels by competitive electrochemiluminescence in plasma samples from 116 adult patients who underwent a myeloablative allogeneic transplantation at Rigshospitalet, Copenhagen between July 2015 and August 2018.ResultsThe median (Q1, Q3) pre-transplantation plasma vitamin D level was 64 (47, 85) nmol/L (normal range: 50–160 nmol/L). Vitamin D insufficiency (<50 nmol/L) and moderate deficiency (<25 nmol/L) were observed in 29% and 8% of patients, respectively. No patients had a severe deficiency (<12 nmol/L). Pre-transplantation vitamin D levels were slightly higher in patients who later developed grade II–IV acute GvHD (mean difference: 8.1 nmol/L), but the 95% confidence interval [CI] encompassed clinically insignificant differences (CI: −2.2, 19.2 nmol/L). From multivariable logistic regression, we found that a patient with a pre-transplantation vitamin D level of 85 nmol/L (Q3) had 1.5 times higher odds of grade II–IV acute GvHD than a patient with a level of 47 nmol/L (Q1; CI of odds ratio: 0.84, 2.7; adjusted for patient age, donor type, use of anti-thymocyte globulin, and use of 12 Gy total-body irradiation). Patients with pre-transplantation vitamin D insufficiency (N = 34) had a cumulative incidence of grade II–IV acute GvHD similar to that of patients with vitamin D sufficiency (26% [CI: 11%, 42%] versus 35% [CI: 25%, 46%], respectively).ConclusionsOur data did not support an association between pre-transplantation vitamin D levels or vitamin D insufficiency and acute GvHD in adult patients receiving myeloablative conditioning. 相似文献
17.
Kalayoglu-Besisik S Yenerel MN Caliskan Y Ozturk S Besisik F Sargin D 《Transplantation proceedings》2005,37(5):2285-2289
Veno-occlusive disease (VOD) of the liver occurs in 10% to 50% of patients after hematopoietic stem cell transplantation (HSCT), ranging from a mild reversible disease to a fulminant course with a mortality rate close to 100%. We retrospectively evaluated the clinical signs, diagnosis, prognosis, therapy, and outcome of 13 hepatic VOD cases which developed after HSCT. A total of 193 consecutive patients (age: 15-62 years; median 33 years) with various hematologic diseases underwent 197 HSCT (allogeneic HSCT, n = 128; autologous HSCT, n = 69). In general, the conditioning regimen consisted of cyclophosphamide combined either with total body irradiation or busulfan. Since 2000, to reduce hepatic complications, all patients received ursodexycolic acid and discontinuation of norethisterone which inhibits ovulation. VOD diagnosed clinically was mainly managed in supportive fashion. Five patients received thrombolytic therapy (t-plasminogen activator [t-PA], n = 3; defibrotide [DF], n = 2). VOD developed in 13 of 197 cases (6.6%). All except one were in the allogeneic group who had received a busulfan-containing conditioning regimen; Ten (77%) were severe. Thirty-three of 197 (17%) cases died before day 100 with VOD as the cause in eight (24%). All of the t-PA administered patients died with significant hemorrhagic complications. DF patients improved completely, even after renal and respiratory failure, despite high total bilirubin levels. Only one patient who received DF became a long-term survivor; the other died with sepsis during the following days. The dramatic improvement with regard to VOD during DF therapy was encouraging. 相似文献
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Survival in ABO-incompatible (ABO-I) liver transplantation has been reported to be between 40% and 60%. Management techniques have included routine immunosuppression as well as prophylactic antilymphoblast globulin, pre- and posttransplant plasmapheresis (PLPH), and splenectomy. Over a 6-year period, 155 orthotopic liver transplants were performed in 139 pediatric patients. Seven children received an ABO-I allograft. In the latter transplants, immunosuppression consisted of triple-drug therapy (cyclosporine A, prednisone, and azathioprine) along with prospective double-volume PLPH for ABO titers (IgA and IgM) greater than or equal to 1:8. Splenectomy was not performed on any patient. One patient was refractory to PLPH and was treated with a hemofiltration system using an immunoadsorption cartridge with synthetic A group antigen. The overall survival for patients receiving ABO-I allografts was 57% (4/7), with a 67% (4/6) graft survival in those patients treated with PLPH. The graft survival for patients treated with prospective PLPH and MALG was 60% (3/5). There was a 60% incidence of rejection in those patients treated with prospective PLPH and these episodes were all mild (steroid bolus only). While ABO-I transplantation is a reasonable option in the emergency setting, further study is necessary before it should be routinely used to increase the general donor organ pool in pediatric liver transplantation. 相似文献
20.
Pihusch M Wegner H Goehring P Salat C Pihusch V Hiller E Andreesen R Kolb HJ Holler E Pihusch R 《Transplantation》2005,80(10):1376-1382
BACKGROUND: Veno-occlusive disease (VOD) is one of the most serious complications following allogeneic hematopoietic stem cell transplantation (HSCT) and is associated with a high mortality. We conducted a large trial in order to investigate the value of plasminogen activator inhibitor-1 (PAI-1) plasma antigen levels in VOD patients as PAI-1 has been described as a possible diagnostic marker of VOD. METHODS: In all, 350 stem cell recipients were included in our study. PAI-1 levels were analyzed prior to conditioning therapy and then weekly until eight weeks after HSCT. Transplantation-related complications (TRC) including VOD, microangiopathic hemolytic anemia (MAHA), and graft-versus-host disease (GVHD) were recorded weekly throughout the study. RESULTS: Maximum PAI-1 antigen levels were increased in all patients with VOD (n=15; mean 248 ng/ml; 95% CI 183-314 ng/ml). Maximum PAI-1 levels above 120 ng/ml showed a sensitivity of 100% and a specificity of 30.6% for VOD after HSCT. CONCLUSION: Our study underlines that maximum PAI-1 plasma antigen levels not exceeding 120 ng/ml have a strong negative predictive value in the diagnosis of VOD and thus represent a helpful non-invasive tool for exclusion of VOD after HSCT. 相似文献