Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methotrexate in combination with a calcineurin inhibitor is a standard graft-versus-host disease (GVHD) prophylactic regimen in allogeneic stem cell transplantation. However, methotrexate is associated with delayed engraftment, mucositis, idiopathic pneumonia syndrome, and other transplant-related complications. Sirolimus, a novel immunosuppressant without methotrexate's toxicities, has been used successfully in solid organ transplantation. We hypothesized that replacing methotrexate with sirolimus would preserve effective prophylaxis of GVHD while minimizing transplant-related toxicity after allogeneic peripheral blood stem cell transplantation. We enrolled 30 patients in a phase II study to test the efficacy of tacrolimus in combination with sirolimus in lieu of methotrexate in preventing GVHD after allogeneic peripheral blood stem cell transplantation from HLA-matched related donors. Grade II GVHD occurred in 3 patients (10%), and no patient developed grade III or IV GVHD. Neutrophil and platelet engraftment were prompt, occurring on days 14 and 13, respectively. All patients survived to hospital discharge (median, 18 days), and peritransplantation toxicity was mild. Four patients developed thrombotic microangiopathy, and 3 patients developed hepatic veno-occlusive disease. Chronic GVHD occurred in 11 patients. Relapse-free and overall survival at 100 days were 93% and 97%, respectively, and were 71% and 67% at 1 year. Causes of death included relapse (n = 6), veno-occlusive disease (n = 1), and late pulmonary toxicity (n = 1). Sirolimus in combination with tacrolimus is a promising alternative to methotrexate-based regimens for GVHD prophylaxis after matched related donor peripheral blood stem cell transplantation. Mucositis was modest, engraftment was prompt, and transplant-related toxicity was modest. Methotrexate-free, sirolimus-based GVHD prophylactic regimens should be tested in randomized trials against the current standard of care.
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PMID:Sirolimus and tacrolimus without methotrexate as graft-versus-host disease prophylaxis after matched related donor peripheral blood stem cell transplantation. 1511 32

Severe metabolic abnormalities occurring within 100 days after allogeneic hematopoietic cell transplantation (HCT) were investigated in 311 patients. The metabolic abnormalities included hyper- and hypocalcemia, hypophosphatemia, hyper- and hypokalemia, hyper- and hyponatremia, hyper- and hypomagnesemia, hypercholesterolemia, hyper- and hypoglycemia, and hyperuricemia. Severe abnormalities, defined as grades III-V by NCI CTCAE v3.0, occurred in 269 patients (86.5%). Multivariate analysis revealed that patients with moderate-to-severe hepatic veno-occlusive disease had significantly higher risk for the occurrence of severe metabolic abnormalities. Grades III-IV acute graft-versus-host disease was the most frequently associated with individual metabolic abnormalities. Patients with at least one severe metabolic abnormality had significantly higher day 100 nonrelapse mortality (P=0.015) and lower 5-year overall survival (P=0.002) than those without severe abnormalities. The number of metabolic abnormalities also stratified the patients with different clinical outcomes. In conclusion, severe metabolic abnormalities occurring within 100 days after allogeneic HCT were common, and their occurrence was significantly associated with inferior clinical outcomes. These results indicate that metabolic parameters should be monitored in patients undergoing allogeneic HCT and that the occurrence of severe metabolic abnormalities should be considered an important toxicity parameter in prospective clinical trials regarding allogeneic HCT.
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PMID:Severe metabolic abnormalities after allogeneic hematopoietic cell transplantation. 1550 52

Blood uric acid levels and purine metabolism are affected in many ways after bone marrow transplantation (BMT). Although BMT is usually performed when patients have a low residual disease burden, a proportion of them are still at risk of tumor lysis syndrome, even with limited disease or after nonmyeloablative conditioning regimens; moreover, an alteration in uric acid turnover can also be observed in patients with persistently normal uric acid blood levels. Apart from this obvious complication, multiple physiopathological events occurring after transplantation may derange uric acid homeostasis. Although there is only indirect evidence (derived from obstetric eclampsia and experimental gout arthritis), a transplant-related increase in cytokine production (particularly TNF, IL-1 and IL-6) may activate xanthine oxidase which, in turn, may be responsible for a further cytokine bout: deranged cytokine homeostasis is involved in the pathogenesis of some of the main acute post-BMT complications, such as hepatic veno-occlusive disease (VOD) and acute graft-versus-host disease (aGVHD). Hyperuricemia is also a well-known side effect of cyclosporine A, the reference drug for the prevention of post-BMT GVHD, which may affect uric acid turnover by reducing glomerular filtration and/or affecting tubular handling; the available evidence favors the former explanation. Hyperuricemia is found in long-term transplanted patients as part of a metabolic pattern reminiscent of the so-called 'X' or 'metabolic'syndrome related to insulin resistance: there is still no precise interpretation of this post-transplant complication nor any definite data concerning its real incidence and outcome. Hyperuricemia is frequently regarded as a marginal finding in the context of X syndrome, but it is pathogenetically linked to the other component of the syndrome and has proved to be autonomously responsible for tissue and vessel damage. Finally, BMT is a possible therapeutic strategy for some inherited forms of hyperuricemia, particularly Lesch- Nyhan disease, although there is still some perplexity concerning the possibility of preventing the development of neurological impairment.
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PMID:Hyperuricemia and bone marrow transplantation. 1560 10

Hematopoietic stem cell transplantation is used to treat hematologic disorders and as an adjunct treatment for solid organ malignancies. After undergoing transplantation, patients are at risk for opportunistic infections and other complications caused by dysfunction of the immune system. Pulmonary complications include cryptogenic organizing pneumonia, opportunistic pneumonias caused by Aspergillus and Zygomycetes species and cytomegalovirus, alveolar hemorrhage, and constrictive bronchiolitis. Abdominal complications include hepatic veno-occlusive disease, graft-versus-host disease (GVHD), colitis, and hemorrhagic cystitis. Allogeneic transplant recipients are at risk for developing GVHD. Autologous and syngeneic transplant recipients are less likely to have chronic or late posttransplantation complications. Nonmyeloablative transplant recipients are less likely to develop opportunistic infections and other complications in the period immediately following transplantation, but are at risk for developing chronic GVHD and other chronic complications. Radiologic evaluation serves as the cornerstone for timely diagnosis of these complications, which is essential to reduce patient morbidity and mortality. Combining clinical factors-including the type of transplant and the point of time during the posttransplantation course-with characteristic imaging features yields the most specific and accurate differential diagnosis for radiologic findings in stem cell transplant recipients.
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PMID:Imaging evaluation of pulmonary and abdominal complications following hematopoietic stem cell transplantation. 1579 50

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).
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PMID:Altered metabolism of tacrolimus in hepatic veno-occlusive disease. 1616 10

Malignant infantile osteopetrosis (MIOP) is a lethal disorder caused by osteoclast dysfunction. The only curative therapy for MIOP is stem cell transplantation (SCT). Because the number of patients is limited, the conditioning regimen and the use of alternative donors for SCT have been controversial and not established. The authors report a case of successful cord blood transplantation (CBT) with a nonmyeloablative regimen (NMR) for MIOP. The patient was a 9-month-old girl with MIOP. Before this diagnosis, she had received chemotherapy under the tentative diagnosis of juvenile myelomonocytic leukemia. She was on mechanical ventilation with tracheotomy due to the progression of MIOP when CBT with NMR was undergone. The conditioning regimen included fludarabine, melphalan, and antithymocyte globulin. Cyclosporine A and methylprednisolone were used for prophylaxis for graft-versus-host disease. Neutrophil engraftment was achieved on day 26 after SCT and has been fully maintained up to the present. Although grade 3 graft-versus-host disease and hepatic veno-occlusive disease occurred, both were controllable. Although the pretransplant condition of our patient was somewhat unusual, this is the first reported case of successful CBT with NMR for MIOP. Because of the urgent need, CBT can be considered as one of the SCT sources for MIOP, especially in a severe, life-threatening setting.
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PMID:Successful nonmyeloablative cord blood transplantation for an infant with malignant infantile osteopetrosis. 1618 44

Hepatic veno-occlusive disease (HVOD) is a serious life-threatening complication of hematopoietic stem cell transplantation (HSCT). Currently, there is no optimal therapeutic strategy and preventive measures are ill-defined. Ursodeoxycholic acid (UA) is well-tolerated oral medication that has been associated with possible benefit as a prophylactic agent. We sought to summarize and quantify the clinical effects of prophylactic UA in the context of HSCT. We undertook a systematic review of studies addressing the use of UA as monotherapy or in combination with other agents in patients undergoing HSCT. The Search Strategy included MEDLINE (1966 to fourth week of March 2006), EMBASE (1980 to fourth week of March 2006), all EBM Reviews (fourth quarter of 2005), Ovid Healthstar (1966 to fourth week of March 2006), and Google Scholar on March 20, 2006. Six studies, 4 randomized clinical trials and 2 historically controlled studies, representing 824 patients were included in the review. Three randomized clinical trials comparing prophylactic UA with no treatment demonstrated reduced proportion of HVOD (relative risk [RR], 0.34; 95% confidence interval [CI], 0.17-0.66). When the analysis was limited to higher-quality studies, the beneficial effect of UA remained significant (RR, 0.36; 95% CI, 0.15-0.90). Transplant-related mortality was also reduced with the prophylactic use of UA (RR, 0.58; 95% CI, 0.35-0.95). UA did not significantly attenuate the outcomes of acute graft-versus-host disease (RR, 0.76; 95% CI, 0.53-1.09), relapse (RR, 0.77; 95% CI, 0.46-1.31), or overall survival (RR, 1.22; 95 % CI, 0.96-1.54). UA appears effective for HVOD prophylaxis in patients undergoing HSCT and should be considered as a prevention strategy by HSCT centers to reduce HVOD.
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PMID:Systematic review of controlled clinical trials on the use of ursodeoxycholic acid for the prevention of hepatic veno-occlusive disease in hematopoietic stem cell transplantation. 1724 26

A cohort of 138 children with 144 hematopoietic stem cell transplantation (HSCT) performed in 1997-2006 were analyzed to evaluate risk factors and mortality predictors of hepatic veno-occlusive disease (VOD). Nineteen patients (13.2%) developed VOD (nine boys, median age 3.5 years) at 1-21 days after HSCT (median 13 days). Age < or =2 years at transplant (odds ratio (OR)=5.25, P=0.011), BU-CY conditioning (OR=5.16, P=0.001), thalassemia major (OR=3.97, P=0.015), platelet engraftment beyond day +21 (OR=8.67, P=0.025) were univariate risk factors for VOD. The first two remained significant in multivariate regression. Seven patients (36.8%) with VOD died, at a median of 44 days post transplant (range, 30-421 days). The 5-year survival was 62%. All surviving patients had normal liver function on follow-up at 0.5-9 years. Patients with VOD had higher 100-day mortality (16.3 vs 9.6%, P=0.024). Mortality predictors included donors other than autologous or matched sibling (hazard ratio (HR)=23.6, P=0.006), hepatic and cutaneous GVHD (HR=8.15, P=0.038), maximal weight gain >9% (HR=6.81, P=0.023), pleural effusion, intensive care unit admission, peak bilirubin >300 micromol l(-1) (HR=13.6, P=0.016), day +21 bilirubin >200 micromol l(-1) (HR=33.9, P=0.001), and rise of bilirubin >15 micromol l(-1) per day within the first week (HR=19.8, P=0.006). Mortality was substantially higher if >3 predictors were present (HR=33.9, P=0.001). Meticulous monitoring in high-risk patients and early treatment should be considered before VOD progresses beyond salvage.
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PMID:Risk factors and mortality predictors of hepatic veno-occlusive disease after pediatric hematopoietic stem cell transplantation. 1776 90

We aimed to evaluate the ADAMTS13 activity weekly after the hematopoietic stem cell transplantation and its relationship with clinical outcome. We studied 30 patients undergoing allogeneic hematopoietic stem cell transplantation with different conditioning regimens and 15 healthy controls. Plasmas were collected from patients 10 days before transplantation, the day of transplantation and 7th, 14th, 21st and 28th days after transplantation. Patients were followed for median period of 13 months (6-24 months). Patient plasmas were further collected when graft versus host disease (GVHD) developed. Enzyme activities of patients did not show a significant change through weeks [87% (39-145), 82% (16-110), 80% (36-134), 80% (36-134), 86% (47-127), 89% (11-127) and 90% (10-127)]. None of our patients had enzyme activity lower than 5% and had thrombotic microangiopathy, thromboembolism or hepatic veno-occlusive disease. Enzyme activity on the day of acute GVHD was not significantly different from the pretransplantation period (73 +/- 32 versus 87 +/- 20%, P = 0.231), but significantly lower than healthy controls (73 +/- 32 versus 97 +/- 16%, P = 0.02). Moreover, by the 28th day after transplantation, patients with acute GVHD had lower enzyme activity than the patients without acute GVHD (62 +/- 36 versus 95 +/- 22%, P = 0.009). ADAMTS13 activity was lower in samples taken from patients with chronic GVHD compared with baseline level (67 +/- 13 versus 91 +/- 30%, P = 0.15) and healthy controls (67 +/- 13 versus 97 +/- 16%, P = 0002). According to our data, transplantation does not have significant effect on ADAMTS13 activity. Acute or chronic GVHD causes a slight decrease of the enzyme that may indicate the possible cytokine effect.
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PMID:Follow-up of ADAMTS13 enzyme and its relationship with clinical events after allogeneic hematopoietic stem cell transplantation. 1965 14

Chemotherapy drugs, biological medications that are used to treat cancer, may cause hepatic side effects. Patients with pre-existing viral hepatitis may be more susceptible to exacerbation of their underlying liver disease, and risk of drug-induced hepatotoxicity. We conducted a search on immunosuppression, and its impact on reactivation of viral hepatitis, using the electro-nic medical databases. Before starting chemotherapy, it is recommended to record the past history of liver disease and check for hepatitis B virus (HBV) and hepatitis C virus (HCV) serology. In immunosuppressed patients, radiation toxicity, graft versus host disease, hepatic veno-occlusive disease, acalculous cholecystitis, tumor infiltration, ischemia, other viruses such as CMV and her-pes virus, and systemic infection should also be considered. Transplant recipients with serologic evidence of previous infection with hepatitis B or C, or those who receive organs from a seropositive donor, should have viral load levels monitored before and after transplantation and, may also require treatment. We believe that there is a role for prophylactic use of antiviral treatment in patients at risk for HBV reactivation.
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PMID:Impact of immunosuppression and chemotherapy on reactivation of viral hepatitis. 2058 63


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