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)

Anemia is common after liver transplantation, with the incidence ranging from 4.3% to 28.2% depending on the criteria used to define anemia. The cause of anemia is unidentified in the majority of patients, and it is likely to be multifactorial. Immunosuppressive-medication-induced bone marrow suppression is perhaps the most common cause of unexplained anemia. Chronic blood loss, iron deficiency, hemolysis, and renal insufficiency are other potential causes of chronic anemia. Rare causes, somewhat unique to transplantation, include aplastic anemia, graft-versus-host disease (GVHD), and lymphoproliferative disease. Anemia due to immunosuppressive medication is challenging, since almost all drugs currently used for this purpose cause anemia, but the renal-sparing property of sirolimus may benefit the subgroup in which renal insufficiency is contributing to anemia. Aplastic anemia is seen in young patients transplanted for non-A, non-B, non-C, fulminant hepatic failure. It is thought to be immunologically mediated, secondary to an unknown viral infection, and is associated with a grave prognosis. GVHD is another infrequent (approximately 1% of transplant recipients) but serious cause of severe anemia that carries a dismal prognosis. Lymphoproliferative disorder, too may rarely rare cause anemia and it may respond to reduction of immunosuppression. Recipients of solid-organ transplants do not mount a significant increase in erythropoietin in response to anemia. In conclusion, though there are no data on the response of anemia to erythropoietin in liver transplant recipients, it appears to benefit other solid-organ-transplant recipients with anemia.
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PMID:Post-liver-transplant anemia: etiology and management. 1476 52

Hematopoietic stem cell transplantation (HSCT) from HLA haploidentical mismatched donors has recently been developed for patients with high-risk acute leukemia who do not have a matched donor. After a high intensity conditioning regimen the HLA barrier is overcome by infusing a graft containing a megadose of T cell-depleted progenitor cells. Nowadays, for graft processing automated peripheral blood CD34(+) cell immunoselection is time and labor saving and ensures a high CD34(+) cell recovery rate. Besides providing 4.5 log T cell depletion of the graft, it guarantees a 3.5 log B cell depletion, which helps prevent EBV-related lymphoproliferative disorders. Excellent engraftment rates are associated with a very low incidence of graft-versus-host disease and regimen-related mortality even in patients who are over 40 years old. Overall, event-free survival and transplant-related mortality compare favorably with reports from unrelated matched transplants. Donor natural killer cell alloreactivity also plays a role in improving outcome in patients with acute myeloid leukemia. These results show the haploidentical transplant to be a viable, alternative source of stem cells for adults with acute leukemia at high-risk of relapse who do not have matched donors, and encourage extending it to patients with an indication to transplant.
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PMID:Transplantation of haploidentically mismatched stem cells for the treatment of malignant diseases. 1537 70

Haploidentical stem cell transplantation has became a clinical reality in the last 10 years as it provides the chance of transplant for about 50% of patients with hematological malignancies who do not have a matched related or unrelated donor. Proper graft preparation for this type of transplant is crucial and this paper analyses our work over the past decade in the search for the optimal graft processing procedure moving from E-rosetting and soybean agglutination, through a combination of negative or positive selection of hematopoietic stem cells to the current method of one-step positive selection. In preparing a graft for haploidentical transplant, three essential requisites must be met. It must contain (1) a megadose (>10 x 10(6) x kg recipient b.w.) of hematopoietic stem cells to overcome the HLA histocompatibility barrier; (2) very few T-lymphocytes (CD3+ cells < 3 x 10(4)/kg recipient b.w.) to prevent severe acute and chronic graft-versus-host disease (GvHD); (3) very few B-lymphocytes to prevent Epstein-Barr virus-related lymphoproliferative disorders. With current graft processing technologies based on positive selection of hematopoietic stem cells, these requirements can be met. A 70-80% hematopoietic stem cell recovery ensures the target megadose is achieved in over 70% of cases with a T-cell depletion of more than 4 logs and a B-cell depletion of over 3 logs. Progress in graft processing has ensured primary, sustained engraftment rates of over 90% and has significantly reduced the incidence of severe acute GvHD and EBV-related lymphoproliferative disorders. Modern time-saving automated graft processing devices ensure reproducibility, reliability, and biological safety, which make widespread application of the haploidentical transplant currently feasible.
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PMID:Graft engineering for allogeneic haploidentical stem cell transplantation. 1552 44

Antilymphocyte/thymocyte globulins (ALGs/ATGs) have now been used for over 30 years in the setting of hemopoietic stem cell transplants (HSCT), with the aim of preventing graft-versus-host disease (GvHD). This is true especially for transplants from alternative donors. In this review, we will be discussing available published and unpublished data on the advantages and disadvantages of using ALG/ATG before or after an allogeneic HSCT. These studies show that ALG/ATG significantly reduce the incidence and severity of acute and chronic GvHD. Unfortunately, they also show that immune deficiency is a more prolonged and infectious complication more frequent in patients receiving ALG/ATG, suggesting the importance of aggressive monitoring of viral and fungal infections. In particular, the emerging problem of Epstein-Barr virus (EBV) infections and EBV-related lymphoproliferative disorders will be discussed, together with the use of pre-emptive therapy with rituximab. I personally believe ALG/ATG has an important role in allogeneic HSCT, especially today with the increasing use of peripheral blood transplants and the consequent high risk of chronic GvHD. ALG/ATG should be used with caution, and the negative consequences must be understood and possibly prevented.
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PMID:Antilymphocyte/thymocyte globulin for graft versus host disease prophylaxis: efficacy and side effects. 1555 41

Results of a previous phase I study suggested that a single 3 mg/m2 dose of the humanized non-FcR-binding anti-CD3 monoclonal antibody visilizumab (Nuvion) was well tolerated and had efficacy for the treatment of steroid-refractory acute graft-versus-host disease (GVHD). We now report results of a multicenter phase II study in which visilizumab was given to 44 participants with steroid-refractory acute GVHD. Eighty-two percent of the participants had visceral involvement, and 86% had overall grade III or IV acute GVHD at study entry. The respective complete and overall response rates were 14% and 32% at 42 days. Plasma Epstein-Barr virus DNA increased to more than 1000 copies per milliliter in 19 subjects. Seventeen received rituximab, and no fatal lymphoproliferative disorders were observed. Survival at 180 days was 32% (95% confidence interval, 18%-46%). The administration of visilizumab as used in this study seems to be sufficiently safe and effective to warrant further assessment for treatment or prevention of GVHD.
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PMID:A phase II multicenter study of visilizumab, humanized anti-CD3 antibody, to treat steroid-refractory acute graft-versus-host disease. 1593 35

Thirty-six patients with chronic B-lymphoproliferative disorders (B-LPD) underwent reduced-intensity allogeneic transplantation (RIT) from HLA-identical related donors. Diagnoses included follicular (n=17), mantle cell (n=9) and small lymphocytic lymphoma (n=2), and chronic lymphocytic leukaemia (n=8). Median age at transplant was 51 years (range, 30-66) and time from diagnosis was 3.4 years (range, 0.3-9.5). At transplant, 28% were in CR, 36% were in PR and 36% were chemorefractory. Conditioning therapy included fludarabine and either cyclophosphamide (n=27) or melphalan (n=9). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin (CsA)/methotrexate (n=21), CsA/mycophenolate mofetil (n=13) or CsA alone (n=2). Eight patients died owing to acute GVHD (n=3), infection in association with chronic GVHD (n=4) and intra-abdominal bleeding (n=1). Treatment-related mortality was 8% at day 100, and 17 and 20% at one and two years, respectively. The cumulative incidence of grade II-IV acute GVHD was 58%, whereas limited and extensive chronic GVHD occurred in 25 and 56%, respectively. No patient has relapsed or progressed. At a median follow-up of 48 months, overall survival probability is 80% (95% CI, 67-93%). We confirm that RIT in chronic B-LPD can result in high and durable CR rates but with significant incidences of acute and chronic GVHD.
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PMID:Reduced-intensity allogeneic haemopoietic stem cell transplantation induces durable responses in patients with chronic B-lymphoproliferative disorders. 1656 35

Bone marrow transplantation is frequently performed to restore hematologic and immunologic competence after chemotherapy and radiation therapy for a range of childhood malignancies, as well as to treat various congenital conditions in which hematologic and immunologic functions are depressed or absent. Potentially devastating complications may occur during the pre-engraftment period after bone marrow transplantation, when marrow aplasia may supervene for several weeks until engraftment occurs, as well as during the post-engraftment period (the 3 months after engraftment) and in subsequent months and years. Complications of bone marrow transplantation may be classified either according to the time interval between transplantation and the occurrence of the complication or according to the organ system affected. The range of complications that may affect the central nervous system and the rest of the body may be detected with ultrasonography, computed tomography, and magnetic resonance imaging. Neurologic, paranasal sinus, pulmonary, and abdominopelvic complications all may be seen after bone marrow transplantation. Graft-versus-host disease and lymphoproliferative disorders also may occur. The increasing use of bone marrow transplantation mandates that the radiologist be familiar with the full range of potential complications and their imaging appearances.
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PMID:Imaging the complications of bone marrow transplantation in children. 1737 55

Disease relapse is the commonest cause of treatment failure after allogeneic haematopoietic stem-cell transplantation. Adoptive immunotherapy based on donor lymphocyte infusions (DLI) has a prominent role in the management of disease recurrence. Although the highest remission rates are achieved in chronic myeloid leukaemia (CML), encouraging results have also been reported in chronic lymphoproliferative disorders. However, the experience of DLI in CML is not necessarily applicable to the management of lymphoproliferative diseases because of the heterogeneity of the conditioning regimens used in chronic lymphoid malignancies. We will review the role of DLI for different disease types in the context of conventional and reduced-intensity conditioning regimens. The factors influencing response and graft-versus-host disease as well as the optimal cell dose will be discussed. Finally, we will describe the main avenues currently being explored to improve the selectivity and efficacy of DLI.
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PMID:Disease relapse after haematopoietic stem cell transplantation: risk factors and treatment. 1744 64

To investigate the efficacy and safety of haploidentical (from family member donors) hematopoietic stem cell transplantation (HSCT) for children. 42 children under 14 yrs old with hematological malignancies underwent haploidentical HSCT. Outcomes were analyzed. Thirty-three children were classified as high-risk candidates. Of 42 patient/donor pairs, 4 (9.5%) were mismatched in 2 HLA loci, 15 (35.7%) in 3 loci, and 23 (54.8%) in 4 loci. Follow-ups were performed for a median of 1110 (449-1959) days after transplantation. All patients achieved stable engraftments. The cumulative incidence of acute graft-versus-host disease (aGVHD) of grade 2-4 was 57.2%, and that of grade 3-4 was 13.8%. The cumulative incidence of chronic graft-versus-host disease (cGVHD) was 56.7% for total and 29.5% for extensive. Twenty-seven patients survived with a 3-yr probability of leukemia-free survival (LFS), 57.3+/-8%, 18 of them were in the high-risk group. Fifteen patients died, 4 from infection, 7 from relapse of leukemia, 2 from heart failure, one from severe aGVHD, and one from lymphoproliferative disorders. The results encourage extending haploidentical HSCT without T cell depletion treatments to children with an indication for transplantation.
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PMID:Haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for treatment of hematological malignancies in children. 1834 90

Disease relapse following an allogeneic transplant remains a major cause of treatment failure, often with a poor outcome. Second allogeneic transplant procedures have been associated with high TRM, especially with myeloablative conditioning. We hypothesized that the use of reduced-intensity conditioning (RIC) would decrease the TRM. We performed a retrospective national multicentre analysis of 71 patients receiving a second allogeneic transplant using RIC after disease relapse following an initial allogeneic transplant. The majority of patients had leukaemia/myelodysplasia (MDS) (N=57), nine had lymphoproliferative disorders, two had myeloma and three had myeloproliferative diseases. A total of 25% of patients had unrelated donors. The median follow-up was 906 days from the second allograft. The predicted overall survival (OS) and TRM at 2 years were 28 and 27%, respectively. TRM was significantly lower in those who relapsed late (>11 months) following the first transplant (2 years: 17 vs 38% in early relapses; P=0.03). Two factors were significantly associated with a better survival: late relapse (P=0.014) and chronic GVHD following the second transplant (P=0.014). These data support our hypothesis that the second RIC allograft results in a lower TRM than using MA. A proportion of patients achieved a sustained remission even when relapsing after a previous MA transplant.
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PMID:Outcome of second allogeneic transplants using reduced-intensity conditioning following relapse of haematological malignancy after an initial allogeneic transplant. 1872 93


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