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)

We retrospectively analysed the outcome of voluntary unrelated donor (VUD)-SCT in 56 patients after conditioning without or with ATG. All received partially lymphocyte-depleted grafts. Four of 17 patients (24%) who were not given ATG rejected their grafts, as did one of 33 (3%) conditioned with ATG (P=0.02). The incidences of acute graft-versus-host disease grade III/IV were 29 and 6%, respectively (P=0.02), and probabilities of 1-year transplant-related mortality were 64% (95% CI, 44-84%) and 27% (95% CI, 12-42%), respectively (P=0.004). Projected at 3 years, probability of survival was 18% (95% CI, 2-34%) after conditioning without ATG and 60% (95% CI, 43-70%) after conditioning with ATG (P=0.002). Probabilities of disease-free survival (DFS) were 18% (95% CI, 2-34%) and 45% (95% CI, 27-63%), respectively (P=0.005). Patients who did not receive ATG had a probability of current DFS of 18% (95% CI, 3-34%) and this was 60% (95% CI, 43-77%) for the patients conditioned with ATG (P<0.001). We conclude that the addition of ATG to the conditioning regimen is associated with a significantly more favourable outcome in recipients of partially T-cell-depleted grafts from VUDs.
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PMID:Addition of ATG to the conditioning regimen is a major determinant for outcome after transplantation with partially lymphocyte-depleted grafts from voluntary unrelated donors. 1506 94

It is difficult to treat lung complications caused by chronic graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). We retrospectively analyzed the characteristics of five patients with mediastinal emphysema (ME) and bilateral pneumothoraces (BP) caused by chronic lung GVHD after allo-SCT. Four of these patients had undergone unrelated SCT, and three had had HLA-identical unrelated donors. All patients received total body irradiation (TBI) during conditioning. Immunosuppressive agents were administered as GHVD prophylaxis, but two patients developed acute GVHD and all the five developed chronic GVHD. The onset of lung complications was 99-1915 days (median, 202 days) after SCT. The onset of ME and BP was 6-48 days (median, 23 days) after the onset of lung complications. Immunosuppressive agents were initially beneficial on the lung complications, but the patients later showed no response to therapy, and all died from respiratory failure 7-195 days (median, 28 days) after the development of ME and BP. The results suggest that these complications progress rapidly, are resistant to treatment, and have a poor prognosis. It is therefore important to start prophylaxis and treatment as early as possible.
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PMID:Mediastinal emphysema and bilateral pneumothoraces with chronic GVHD in patients after allogeneic stem cell transplantation. 1506 95

In all, 41 multiple myeloma (MM) patients received an antithymocyte globulin (ATG), fludarabine, and busulfan-based reduced intensity conditioning (RIC) for allogeneic stem cell transplantation (allo-SCT) from HLA-identical siblings. In total, 29 patients (70%) were in partial remission, one patient in complete remission, and 11 (27%) with progressive disease at the time of allo-SCT. Median time between diagnosis and allo-SCT was 24 months. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) were 36% (95% CI, 21-51%) and 7% (95% CI, 2-20%), respectively. Overall, 10 patients developed limited chronic GVHD, whereas seven developed an extensive form (cumulative incidence, 41% (95% CI, 26-56%) at 2 years). With a median follow-up of 389 days, the overall cumulative incidence of transplant-related mortality (TRM) was 17% (95% CI, 6-28%). In all, 11 patients (27%) are in continuous complete remission, and the Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) at 2 years were 62% (95% CI, 47-76%) and 41% (95% CI, 23-62%), respectively. PFS and OS were significantly higher in patients with chronic GVHD as compared to patients without chronic GVHD (P=0.006 for PFS and P=0.01 for OS). Collectively, these data demonstrate that RIC allo-SCT can mediate a potentially curative graft-versus-myeloma effect with an acceptable incidence of toxicity and TRM.
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PMID:Graft-versus-myeloma effect following antithymocyte globulin-based reduced intensity conditioning allogeneic stem cell transplantation. 1513 85

Complementarity-determining region (CDR3) size spectratyping has often been used to analyze the clonal expansion of T-cells. CDR3 size spectratyping has been useful in the analysis of the oligoclonal expansion of T-cells in virus infection, graft-versus-leukemia effect (GVL), graft-versus-host disease (GVHD), and immune reconstitution of T-cells after allogeneic stem cell transplantation (allo-SCT). We analyzed 26 T cell receptor (TCR)-beta-chain subfamilies (VB) in 25 patients who underwent allo-SCT. Fifteen of these patients developed acute GVHD (aGVHD). Many TCR-VB were skewed in the early stage. In these TCR-VB subfamilies, VB6 was most often skewed at the time of skin aGVHD. We then analyzed the average score of the complexity of 26 TCR-VB spectratypings in patients with or without cGVHD. The patients who developed chronic GVHD (cGVHD) had a lower average score of TCR-VB complexity than that of patients without cGVHD (P = 0.010). In particular. the patients who developed the quiescent type and de novo type of cGVHD from 4 months after allo- SCT had a lower average score of TCR-VB complexity at 3 months than that of the patients who had no cGVHD (P = 0.0055). These results suggest that we might be able to consider a possible development of cGVHD by analyzing TCR-VB spectratyping after allo-SCT.
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PMID:Molecular analysis of T-cell repertoire in patients with graft-versus-host disease after allogeneic stem cell transplantation. 1516 Sep 9

The aim of this study was to investigate if graft-versus-leukemia (GVL) activity conferred by allogeneic stem cell transplantation (allo-SCT) is effective in chronic lymphocytic leukemia (CLL) with unmutated V(H) gene status. The kinetics of residual disease (MRD) were measured by quantitative allele-specific immunoglobulin heavy chain (IgH) polymerase chain reaction (PCR) in 9 patients after nonmyeloablative allo-SCT for unmutated CLL. Despite an only modest decrease in the early posttransplantation phase, MRD became undetectable in 7 of 9 patients (78%) from day +100 onwards subsequent to chronic graft-versus-host disease or donor lymphocyte infusions. With a median follow-up of 25 months (range, 14-37 months), these 7 patients remain in continuous clinical and molecular remission. In contrast, PCR negativity was achieved in only 6 of 26 control patients (23%) after autologous SCT for unmutated CLL and it was not durable. Taken together, this study shows for the first time that GVL-mediated immunotherapy might be effective in CLL with unmutated V(H).
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PMID:Graft-versus-leukemia activity may overcome therapeutic resistance of chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene status: implications of minimal residual disease measurement with quantitative PCR. 1520 68

Antithymocyte globulin (ATG) is increasingly used in pre-allogeneic stem cell transplantation (allo-SCT) conditioning regimens to prevent graft rejection and graft-versus-host disease. However, ATG was also found to be associated with increased incidence of thrombosis during organ transplantation. In the present study, we tested the coagulation status of 21 patients with hematologic malignancies undergoing allo-SCT who received ATG-based (11 patients) or non-ATG-based (10) conditioning treatment. We assessed several thrombophilia markers as well as circulating total and endothelial microparticles (TMP/EMP) and soluble CD40 ligand (CD40L). No significant difference in the mean values of prothrombin time, partial thromboplastin time, fibrinogen, antithrombin, protein C, protein S, thrombin-antithrombin III complex, homocysteine levels, prevalence of genetic thrombophilia markers and levels of EMP, TMP or CD40L was observed between the ATG-treated and ATG-untreated patients, as well as before and after conditioning in each group separately. Platelet counts decreased significantly in ATG-treated patients; however, this decrease was not associated with clinical or laboratory evidence of disseminated intravascular coagulation. No patient developed thromboembolic event or veno-occlusive liver disease. Our results suggest that allo-SCT is not associated with increased hypercoagulability and addition of ATG to conditioning regimen has no significant procoagulant effect.
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PMID:Assessment of the coagulation profile in hemato-oncological patients receiving ATG-based conditioning treatment for allogeneic stem cell transplantation. 1524 31

In patients with poor-risk relapse of aggressive lymphoma, reduced-intensity conditioning followed by allogeneic PBSCT may have its limitations because of rapid regrowth of the tumor. We tried to address this problem by intermediate-intensity conditioning followed by allogeneic SCT. A total of 21 patients received fludarabine, busulfan and cyclophosphamide prior to allogeneic SCT. In the first 10 patients, GVHD prophylaxis by CD34+ selection of the grafts was employed (group I). The next 11 patients received nonmanipulated grafts and mycophenolat mofetil plus cyclosporinA (group II). In group I, no GVHD was observed. In contrast, patients in group II had a significant risk of acute GVHD (aGVHD) (six patients with grade II-IV acute GVHD). However, in group I, all surviving patients progressed within 9 months. In contrast, eight of nine surviving patients of group II remain in remission after a median observation time of 10.5 months (range 4-22 months). Survival differed significantly between the groups (P=0.004). Multivariate analysis identified intensive GVHD prophylaxis as important risk factor for survival. These results support the existence of a clinically relevant GVL effect in aggressive lymphoma. T-cell depletion (or CD34 selection) of grafts is not recommended in patients with poor-risk aggressive NHL.
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PMID:Reduced-intensity conditioning prior to allogeneic transplantation of hematopoietic stem cells: the need for T cells early after transplantation to induce a graft-versus-lymphoma effect. 1527 7

Cutaneous T-cell lymphomas (CTCL) are rare diseases that, in their advanced stages or in transformation, have a poor prognosis. Autologous stem cell transplantation (Au-SCT) after high-dose therapy has yielded disappointing results. Allogeneic transplantation (allo-SCT) provides the potential advantage of an immune-mediated graft-versus-lymphoma (GVL) effect. Reduced-intensity allo-SCT potentially offers a GVL effect, but with diminished toxicity related to the induction regimen; however, published experience with this approach in CTCL is limited. We report a series of three patients (age 35-49) with advanced, refractory (n=2) or transformed (n=1) CTCL who underwent reduced-intensity allo-SCT in the context of active disease. All three survived the peri-transplant period and, despite later having disease relapse, all exhibited evidence of a GVL effect. Relapses of the disease were in the context of immune suppression for graft-versus-host disease (GVHD), and when immune suppression was reduced, responses were regained. A comparison is made of these results to those in a review of the published literature to date. We conclude that while a GVL can be achieved for CTCL with reduced-intensity allogeneic transplantation, the clinical benefits are short lived and novel approaches are required to obtain sustained remissions.
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PMID:Graft-versus-lymphoma effect in refractory cutaneous T-cell lymphoma after reduced-intensity HLA-matched sibling allogeneic stem cell transplantation. 1528 86

The use of reduced intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT) can result in a significant decrease in early procedure-related toxicity in patients not eligible for standard myeloablative regimens. However, acute graft-versus-host disease (aGVHD) remains a matter of concern after RIC allo-SCT, and its incidence might be expected to be higher in elderly and high-risk patients. This report investigated mycophenolate mofetil (MMF) and cyclosporin A (CsA) combination (n=14) in comparison to CsA alone (n=20) for GVHD prophylaxis in cancer patients aged over 50 years (27 haematological malignancies and seven solid tumours) receiving an HLA-identical sibling antithymocyte-globulin (ATG)-based RIC allo-SCT. Baseline demographic characteristics and risk factors for aGVHD were comparable between both groups. Although MMF administration was not associated with any significant toxicity, the cumulative incidence of any form of GVHD was comparable between both groups (cumulative incidence of grade II-IV aGVHD, 50% (95% CI, 28-72%) for CsA alone, as compared to 64% (95% CI, 39-89%) to CsA and MMF, P=NS), suggesting that adjunction of MMF to CsA is feasible, but does not translate towards a significant reduction of aGVHD, at least in the context ATG-based RIC allo-SCT.
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PMID:Mycophenolate mofetil and cyclosporine for graft-versus-host disease prophylaxis following reduced intensity conditioning allogeneic stem cell transplantation. 1528 87

Invasive fungal infections (IFI) are common in allogeneic SCT recipients. We have reviewed our experience of IFI with special reference to candidaemia in 685 adult patients transplanted in 1983-2002. The donor was a matched sibling in 505 patients and an unrelated donor in 180 patients. A BM graft was used in 561 patients and a PB graft in 124 patients. Fluconazole prophylaxis was not used during the study period. Definite or probable IFI was observed in 60 patients (8.7%) with a dominance of Aspergillus infections (46 patients, incidence 6.7%). Candidaemia was found only in nine patients (1.3%). The causative agents were Candida albicans (n=8), C. krusei (n=2), and C. glabrata (n=1); in two patients, two causative agents were found. The median time to the diagnosis of candidaemia was 53 days (range 6-249 days) post transplant. Seven patients were neutropaenic at diagnosis, and four patients had experienced acute GVHD. All patients received antifungal therapy, but only one patient was cured. According to this study, candidaemia was a rare event in allogeneic SCT recipients. Thus, systematic prophylaxis against Candida infections might not be indicated. The prognosis of established infections is still poor due to comorbid conditions, notably GVHD.
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PMID:Candidaemia in allogeneic stem cell transplant recipients: low risk without fluconazole prophylaxis. 1551 9


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