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

A murine model of allogeneic bone marrow (BM) transplantation was used to determine the relative importance of CD4+ and CD8+ T cells in establishing donor T cell chimerism and in the development of graft-versus-host (GVH) and graft-versus-leukemia (GVL) reactivity. Mature donor T cells were essential for complete chimerism when host mice (AKR, H-2k) were conditioned with suboptimal irradiation (9 Gy = LD50). Transplantation of donor BM (B10.BR, H-2k) resulted in mixed chimerism, whereas mice given BM containing additional T cells developed into complete and stable chimeras. Depletion of T cell subsets was associated with an increase in the frequency of mixed chimerism. The incidence of lethal GVHD was dependent on the number of T cells added to the BM inoculum. Ex vivo depletion of CD4+ T cells eliminated GVH-associated mortality. Removal of CD8+ T cells had no effect on overall survival. In contrast to the GVH results, removal of either CD4+ or CD8+ T cells compromised GVL reactivity, indicating that an optimal GVL response required both CD4+ and CD8+ T cells. T cell-subset depletion did not interfere with the induction of donor-host tolerance in these chimeras and may have facilitated its development. The loss of GVH/GVL effector cells as a result of T cell depletion and the development of donor-host tolerance may act synergistically to prevent or suppress GVH and GVL reactivity.
 ...
PMID:Contribution of CD4+ and CD8+ T cells to graft-versus-host disease and graft-versus-leukemia reactivity after transplantation of MHC-compatible bone marrow. 183 16

Bone marrow transplantation has become an accepted procedure for the treatment of severe aplastic anemia, hematologic malignancies (particularly lymphoma and leukemia) and certain inborn errors of metabolism and immunity. However, numerous complications follow bone marrow transplantation. Liver disease is a very common and complex complication after human transplantation. The major complications are: veno-occlusive disease, graft-versus-host disease acute and/or chronic. In this decade, the results of bone marrow transplantation will enhance.
 ...
PMID:[Hepatic complications of bone marrow transplantation]. 184 69

Autologous bone marrow transplantation (Auto-KMT) involves harvesting of a portion of a patient's bone marrow for subsequent reinfusion and restoration of marrow function following ablative doses of cytotoxic therapy, used in the treatment of various malignancies. The use of autologous rather than allogeneic marrow stem cells reduces the probability of acute graft-versus-host disease and reduces the need for obtaining HLA-matched marrow from limited donor pools. The greatest problem in Auto-KMT involves efficacy of the cytotoxic therapy and the obvious lack of graft-versus-leukemia effect. In addition, a theoretical limitation is that the marrow may contain clonogenic malignant cells, which may be the source of reestablished disease. In absence of phase III clinical trials directly comparing Auto-KMT with conventional therapies in the treatment of most malignancies, its role continues to be poorly defined. In an attempt to identify subsets of patients with leukemia or lymphoma who might benefit from transplantation, we performed this study of recent reports from the literature. It is concluded that the associated mortality is acceptable. At present the indications for Auto-KMT are lymphoma in relapse after conventional therapy and acute myeloblastic leukemia in second remission. It is probable that Auto-BMT will be used in earlier disease stages in the future (first remission).
 ...
PMID:[Autologous bone marrow transplantation in malignant hematologic diseases]. 185 58

In conclusion, graft-versus-leukemia is important to prevent leukemia relapse following allogeneic bone marrow transplantation. This beneficial GVL effect is at least partly mediated by T-lymphocytes and is greatest in transplants from HLA-nongenotypically identical donors. GVL is associated with the presence of GVHD, although preliminary studies suggest it may be possible to separate these two processes. Improvement in treatment results requires innovative effective therapies to enhance the direct antineoplastic effects of the preparative regimen or immune-mediated antileukemia mechanisms.
 ...
PMID:Immunobiology of bone marrow transplantation as treatment for hematologic malignancies. 187 28

Children with hematological malignancies (n = 33), severe aplastic anemia (SAA, n = 7) and other non-malignant diseases (n = 4) were followed for cataract development after bone marrow transplantation (BMT). The children with hematological malignancies were subjected to total body irradiation (TBI), 10 Gy, in one session with no shielding of the eyes as part of their conditioning regimen before BMT. The children with SAA or other non-malignant diseases received either no irradiation before BMT or a reduced dose, 8 Gy, with shielding of their eyes. After 3 years all patients who had undergone BMT for hematological malignancies had developed lens opacification. No patients in the other groups, without leukemia, showed any sign of cataract development. There was no relationship between steroid treatment for graft-versus-host disease and cataract development. No relation to age of onset of treatment or to the sex of the patient and cataract formation was seen. It seems evident from the present study that TBI given in one session was the main cause of cataract development after BMT.
 ...
PMID:The development of cataract in children as a late side-effect of bone marrow transplantation. 187 89

Results of 470 bone marrow transplants from related donors other than genotypically HLA-identical siblings (alternative related donors) were analysed to identify factors associated with transplant outcome and to determine whether T cell depletion improved results. As compared to 3648 transplant from HLA-identical siblings, alternative related donor transplants were associated with increased graft failure, increased acute graft-versus-host disease (GVHD), and lower disease-free survival. The likelihood of adverse outcome correlated with increasing donor-recipient HLA-disparity. In multivariate analysis of alternative related donor transplants, donor age greater than or equal to 30 years, (relative risk [RR] 1.7, p less than 0.006), intermediate and advanced leukemia (RR 1.5 and 1.6, p less than 0.01 and p less than 0.003), infection pretransplant (RR 1.7, p less than 0.005) and 2- and 3-locus donor-recipient HLA-disparity (RR 1.3, p less than 0.04) were associated with increased risks of treatment failure. The 2-year probability of leukemia-free survival after alternative related donor transplants (n = 43) with none of these adverse prognostic features was 44% (95% confidence interval 28-59%) compared to 56% (95% confidence interval 52-59%) for similar patients receiving HLA-identical sibling transplants (n = 868, univariate p less than 0.03). T cell depletion increased graft failure and decreased acute GVHD after alternative related donor transplants but did not improve leukemia-free survival.
 ...
PMID:Bone marrow transplantation from related donors other than HLA-identical siblings: effect of T cell depletion. 187 91

A combination of cyclosporine (CSA) and methylprednisolone (MP) was used as graft-versus-host disease (GVHD) prophylaxis in 25 patients age 11-47 years (median 27 years) who received HLA-compatible sibling marrow transplants after myeloablative therapy for leukemia, myelodysplasia or lymphoma. CSA was initiated at 3 mg/kg/day in two divided doses, and the dose was adjusted to maintain a trough whole blood h.p.l.c. concentration between 200 and 800 ng/ml. While on i.v. CSA, the dose of CSA was increased for 10 of the 25 patients. The actuarial rate of grades II-IV acute GVHD was 37%. Those patients who developed moderate to severe GVHD had a significantly higher early mortality than those who did not (56% vs 12%, p = 0.02). There was a significant association between the development of acute GVHD and a mean week 2 CSA trough concentration less than 250 ng/ml. Life threatening regimen-related toxicities in the first 100 days included capillary leak syndrome, acute pancreatitis and small bowel perforation. Although the combination of CSA and MP in this dosing schedule was active in preventing acute GVHD, nephrotoxicity remained a problem, and outcome was limited by the inability to achieve the target CSA trough concentration in a substantial proportion of patients.
 ...
PMID:Cyclosporine and methylprednisolone after allogeneic marrow transplantation: association between low cyclosporine concentration and risk of acute graft-versus-host disease. 187 93

Graft-versus-host disease (GVHD) in leukemia patients following allogeneic bone marrow transplantation (BMT) has a lot of demerits but it also has a merit, namely graft-versus-leukemia effect. We reported the results of our recent trials on prevention, treatment and induction of GVHD, and prevention of viral infection after BMT. The results were as follows: 1) Twenty-four percent of patients who received prophylactic administration of cyclosporine and short term methotrexate still developed II degree-IV degree acute GVHD. 2) Patients with I degree or II degree acute GVHD showed good clinical courses. But, most patients with III degree GVHD gradually developed chronic GVHD. All patients with IV degree GVHD died of GVHD or infection. 3) Mizoribine and deoxyspergualin were effective for steroid-resistant GVHD. 4) Bestatin was administered to recipients who did not develop GVHD until day 30 after BMT. An interim report suggests that bestatin may induce chronic GVHD and suppress the relapse of leukemia. 5) Oral administration of gamma-globulin may prevent viral enteritis. Intravenous administration of anti-cytomegalovirus monoclonal antibody may prevent cytomegalovirus pneumonia.
 ...
PMID:[Control of graft-versus-host disease and infection associated with immunosuppression]. 190 15

We analyzed the effects of T-cell depletion on the outcome of HLA-identical sibling bone marrow transplants for leukemia by comparing 731 T-cell-depleted transplants with 2,480 non-T-cell-depleted transplants. T-cell depletion decreased acute graft-versus-host disease (GVHD) (relative risk [RR] 0.45; P less than .0001) and chronic (GVHD) (RR 0.56; P less than .0001). However, it increased graft failure (RR 9.29; P less than .0001). Leukemia relapse also was increased. In first remission acute leukemia or chronic phase chronic myelogenous leukemia, leukemia relapse was 2.75 times more likely after T-cell-depleted transplants (P less than .0001). T-cell depletion increased the risk of treatment failure (RR 1.35; P less than .0003) and decreased leukemia-free survival. We also studied controllable variables associated with outcome of T-cell-depleted transplants. The unique findings were that among recipients of T-cell-depleted transplants for early leukemia, radiation doses greater than or equal to 11 Gy (RR 0.54; P less than .01), dose rates greater than 14 cGy/min (RR 0.56; P less than .002), and additional posttransplant immune suppression with cyclosporine alone (RR 0.53; P less than .0006) or cyclosporine plus methotrexate (RR 0.36; P less than .01) were associated with fewer treatment failures. Use of monoclonal antibodies rather than physical techniques for T-cell depletion (RR 2.01; P less than .03) and fractionated radiation (RR 1.69; P less than .05) were associated with increased treatment failure and lower leukemia-free survival. These data may be useful in designing strategies to improve results of T-cell-depleted transplants.
 ...
PMID:T-cell depletion of HLA-identical transplants in leukemia. 191 89

Bone marrow transplantation has become widely used in the treatment of aplastic anemia and leukemia. Cyclosporine is used as prophylaxis against graft-versus-host disease. The authors report on eight cases of optic disc edema in patients taking cyclosporine after allogenic bone marrow transplant. Thorough evaluation revealed a possible alternate cause in two cases. In all cases, the optic disc edema resolved after discontinuing or decreasing the cyclosporine. Although cyclosporine has not previously been associated with optic disc edema, it has been implicated as the cause of a variety of neurologic side effects. Bone marrow transplant patients taking cyclosporine should be followed for the development of optic disc edema.
 ...
PMID:Optic disc edema after bone marrow transplantation. Possible role of cyclosporine toxicity. 192 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>