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)

It is now possible to access more than one million HLA-A, B typed volunteer individuals willing to donate marrow and a preliminary search through the NMDP registry provides access to more than 200,000 HLA-A, B, DR typed donors. Fifty-four percent of preliminary searches yield at least one potentially HLA-matched donor but the majority of these successful searches involve patients of Caucasian origin. Substantially greater recruitment must occur among different racial and ethnic groups if minority patients are to have a better chance of finding an HLA match. This can be accomplished by recruiting diverse donors within each regional registry or by expanding worldwide the existing international registry network. Molecular typing and matching for alleles in the HLA-D region improve the precision of donor selection and the timeliness of the donor search process. Although the risk of GVHD in unrelated donor transplants remains higher than in HLA-identical sibling transplant is not as good as HLA-identical sibling transplants, newer methods of supportive care and GVHD control are providing and gradual improvement in both the safety of the procedure and long-term relapse-free survival.
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PMID:Marrow transplants from HLA matched unrelated donors: an NMDP update and the Seattle experience. 792 Feb 94

HLA antigens are the major barrier to successful transplantation. Three of the seven heterodimers (HLA-A, -B, and -DR) contribute most to the immunogenicity of a mismatched organ. Although classical serology has been used in the past to phenotype donors and recipients, histocompatibility laboratories are increasingly turning to DNA-based methods to directly genotype patients and donors for the alleles of the HLA complex. Some methods are still evolving, while several others are established well enough to use in the clinical laboratory. The application to solid organ transplantation will result in greater accuracy and a better correlation between HLA matching and graft survival in the future. In fields such as bone marrow transplantation, where matching is critically important for prevention of graft-versus-host disease and engraftment, molecular HLA testing is already being mandated by the transplantation community.
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PMID:HLA molecular typing. 792 29

One hundred and fourteen patients with hematological malignancies received bone marrow transplantation from donors other than HLA-identical siblings. Sixty-three patients received transplantations from related donors; 20 were phenotypically identical for HLA-A, B, D/DR (RM0). 32 differed at one locus (RM1) and 11 differed at more than one loci (RM2). Fifty-one transplantations were from unrelated donors; 37 were phenotypically identical and mixed lymphocyte culture (MLC) negative (UR0) and 14 were MLC positive (UR1). One hundred and four patients had durable engraftment. Four (RM1(1), RM2(2), UR0(1)) failed to achieve engraftment. In terms of the probability of > or = Grade II acute graft-versus-host disease (GVHD), there was no significant difference among the groups according to HLA disparity (RM0:25%, UR0:33%, UR1:39%, RM1:47%, and RM2:50%). The probability of chronic GVHD was significantly higher in UR0 and UR1 than RM0 (71%, 75% vs 28%, p < 0.05). The disease-free survival at 3 years was 45% (RM0), 50% (RM1) and 42% (UR0). More than 50% of patients other than RM0 died of fatal complications including GVHD within 60 days after grafting. In conclusion, unrelated donor and related donor mismatched at one locus could be selected for marrow graft in the case of the absence of an HLA-matched related donor. However, more advances in post-transplant management and in histocompatibility testing should be required.
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PMID:[Bone marrow transplantation from donors other than HLA matched siblings for hematological malignancies. Nagoya Bone Marrow Transplantation Group and Tokai Marrow Donor Bank]. 793 58

It is now possible to access more than 1 million HLA-A, B typed volunteers willing to donate marrow. A preliminary search through the U.S. NMDP provides direct computerized access to the HLA-A, B, DR phenotypes of more than 186,000 registered donors. Fifty-one percent of preliminary searches yield at least one HLA-A, B, DR match, but a disproportional number of successful searches benefit primarily patients of Caucasian origin. Substantially greater recruitment among different racial and ethnic groups must occur if non-Caucasians are to have a better chance of finding an HLA-matched donor. Improved cooperation between registries and transplant networks in different countries remains an important goal. The optimal application of URD transplants may not be possible until an efficient and reliable worldwide marrow donor program has been established. DNA typing and matching for HLA alleles improves the timeliness of the donor search process and the precision of donor selection. HLA mismatching increases the probability and severity of GVHD, but minor mismatches for one HLA-A, B, or D/DRB1 locus does not appear to decrease survival. Although the risk of GVHD in URD transplants remains high and survival currently is not as favorable as HLA identical sibling transplants, better supportive care and GVHD control are providing a gradual improvement in the long-term disease-free survival of URD transplants.
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PMID:Marrow transplants from unrelated donors. 803 96

To characterize skin-infiltrating T lymphocytes during acute GVHD, skin biopsies were obtained from two patients who received unrelated marrow matched for HLA-A, -B, -DR, and -DQ but mismatched for -DP. A total of 120 T-cell clones were generated. Phenotype analysis of the clones showed that the majority of cells were CD4+ and expressed alpha/beta TCR. HLA-DP oligonucleotide genotyping of the clones revealed the presence of lymphoid chimerism. PLT assay showed the lack of HLA specificity, including mismatched HLA-DP. However, mAb to HLA antigens blocked proliferation of the majority of the clones, indicating that the clones recognized HLA-associated molecules. Interestingly, proliferation of two CD4+ T-cell clones was inhibited by class I mAb. A few of the clones revealed augmented proliferation in the presence of CMV antigens and a few revealed cytolytic activity. The above study suggests that (a) CD4+ helper T cells may be primarily responsible for immunopathogenesis of skin manifestations during acute GVHD, (b) there is a mixed lymphoid chimerism in skin during acute GVHD, (c) HLA-DP may not be a factor contributing to the development of acute GVHD, (d) the peptide of the HLA groove or superantigen associated with HLA molecules may be the stimulatory antigen, and (e) CMV antigens appear to stimulate some of the skin-infiltrating T lymphocytes.
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PMID:Characterization of skin-infiltrating cells during acute graft-versus-host disease following bone marrow transplantation using unrelated marrow donors. 804 93

Recent studies have shown that host-reactive interleukin-2 (IL-2)-secreting donor T lymphocytes (TI) are critically involved in the development of acute graft-versus-host disease (GVHD) after allogeneic HLA-identical sibling bone marrow transplantation (BMT). To further characterize the responding TI, we determined the frequency of pretransplant IL-2-secreting TI-precursors (TI-p) between eight HLA-A, -B, -C, -DR, and -DQ-identical sibling donor-host pairs in both the graft-versus-host (GVH) and the host-versus-graft (HVG) direction. High frequencies of pretransplant host-reactive donor TI-p (1/18,000 to 1/49,000) were detectable in five patients with grade II acute GVHD. Donor-reactive host TI-p (1/3,700 to 1/31,000) were observed in previously in vivo primed (n = 5) and unprimed (n = 1) patients. In two pairs tested after previous in vivo priming, pretransplant donor-reactive host TI-p were highly enriched within the CD45RO+ memory T-cell subset. Previously unprimed host-reactive donor TI-p occurred in almost equal frequencies within CD45RO+ and CD45RO- T cells. Both CD4+ and CD8+ T-cell subsets contributed in comparable frequencies to host- and donor-reactive TI-p. Recognition of minor histocompatibility (mH) antigens by CD8+ TI-p appeared to be class I major histocompatibility complex (MHC)-restricted, whereas CD4+ TI-p operated in a class II (HLA-DR) MHC-restricted fashion. Even between oligonucleotide-defined HLA-DPB1-disparate sibling donor-host pairs (n = 3), either responding T-cell subset was found to recognize cellularly defined mH antigens. These data indicate that various T-cell subsets contribute to host- and donor-reactive IL-2-secreting TI in allogeneic sibling BMT.
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PMID:Pretransplant detection of human minor histocompatibility antigen-specific naive and memory interleukin-2-secreting T cells within class I major histocompatibility complex (MHC)-restricted CD8+ and class II MHC-restricted CD4+ T-cell subsets. 810 Jul 22

A patient without evident immune deficiency who received a transfusion of blood from a second-degree family member developed fatal transfusion-associated graft-versus-host disease (TA-GVHD). The donor was homozygous for an HLA haplotype for which the recipient was heterozygous (one-way HLA match). All 39 reported cases of TA-GVHD in immunocompetent patients were reviewed to ascertain the predisposing factors and to define the indications for irradiating blood for this population. HLA typing was described in 15 cases; in 13, including seven related and six unrelated donors, a one-way HLA match was present. Thirty-one (79%) of the 39 cases were reported from Japan (and 196 other cases are cited in the Japanese literature), but a one-way HLA match among unrelated donors at HLA-A, -B, -DR loci is only approximately two to four times more likely in Japanese persons than in whites. Fresh blood (< 96 hours old) was used in 29 (94%) of the 31 cases reported from Japan and in 33 (87%) of 38 cases overall (in one case, the age of the blood used was not reported). Thus, factors that appear to predispose to TA-GVHD in immunocompetent patients are a one-way HLA match, fresh blood, and, possibly, Japanese ancestry. Irradiating cellular blood components from all blood relatives of transfusion recipients will not completely eliminate the risk of TA-GVHD.
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PMID:Transfusion-associated graft-versus-host disease in immunocompetent patients: report of a fatal case associated with transfusion of blood from a second-degree relative, and a survey of predisposing factors. 821 11

BMT from matched unrelated donors or mismatched family members is associated with an increased risk of graft-versus-host disease (GVHD) compared with HLA-identical sibling donors. It has been suggested that the level of patient-specific CTL precursors (CTLp) present in matched unrelated donors correlates with the incidence and severity of GVHD after BMT. This study group consisted of 17 patients who all received unmanipulated bone marrow from an HLA-A,B,DR-matched unrelated donor. Patient-specific CTLp frequencies were estimated in the donor before transplant. The CTLp frequencies were then compared with the incidence and severity of GVHD experienced by the patient after transplantation. Statistical analysis revealed no correlation between donor precursor frequencies and the patient developing clinically significant acute GVHD after transplantation (X2 = 1.16). This study suggests that caution should be used before the inclusion of the CTLp frequency result in the clinical decision of selecting the most suitable matched unrelated donor for BMT. CTLp frequency does not correlate with either the incidence or severity of GVHD after matched unrelated donor BMT.
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PMID:Cytotoxic T lymphocyte precursor frequency does not correlate with either the incidence or severity of graft-versus-host disease after matched unrelated donor bone marrow transplantation. 814 Jun 31

Between January 1988 and March 1993, 48 patients received T-cell-depleted marrow grafts from unrelated donors as treatment for chronic myelogenous leukemia (CML). The median age of the population was 31.7 years (range 5.4 to 53) with 17 of 48 patients greater than 40 years of age. Twenty-seven patients were transplanted in chronic phase, 17 in accelerated phase, and 4 in blast crisis. All patients received a standardized preparative regimen of cyclophosphamide, high-dose cytosine arabinoside, methylprednisolone, and total body irradiation. Marrow grafts were depleted of mature T cells with the alpha beta T-cell receptor antibody T10B9 as graft-versus-host disease (GVHD) prophylaxis. All patients also received posttransplant cyclosporine therapy. Twenty-eight of 48 patients were mismatched with their donors for one or more HLA-A, B, DR, or DQ loci by either serology or high-resolution oligonucleotide genotyping. Nine of 28 were mismatched at multiple HLA loci. Durable engraftment was achieved in 94% (45/48) of patients. The actuarial probability of developing grades II to IV and grades III to IV acute GVHD were 39.6% (95% confidence interval (CI) 26.9 to 53.0) and 8.3% (95% CI 6.1 to 10.9) for the entire cohort. There was no difference in the incidence of grades II to IV acute GVHD between patients receiving matched (36.8%) or mismatched (41.4%) marrow grafts (P = .77). The actuarial probability of relapse at 2 years was 8.8% (95% CI 2.1 to 21.6) for the entire cohort and 18% (95% CI 4 to 41) for patients transplanted in either the accelerated or blast crisis phase (advanced disease). One cytogenetic relapse has occurred among patients transplanted in the chronic phase. The probability of disease-free survival at 2 years was 52% (95% CI 24 to 70) for patients transplanted in chronic phase and 46% (95% CI 25 to 73) for patients transplanted with advanced disease. No difference in disease-free survival was observed between patients receiving matched (49%) or mismatched (51%) marrow grafts (P = .90). This study shows that patients receiving unrelated T-cell-depleted marrow grafts for CML can achieve durable engraftment with a low incidence of severe GVHD and apparent preservation of graft-versus-leukemia reactivity. These data also suggest that T-cell depletion may allow patients who might otherwise experience unacceptable toxicity from GVHD-related complications caused by older age or increased HLA disparity to benefit from unrelated marrow grafts.
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PMID:Effect of T-cell depletion as graft-versus-host disease prophylaxis on engraftment, relapse, and disease-free survival in unrelated marrow transplantation for chronic myelogenous leukemia. 814 64

Transfusion-associated graft-versus-host disease (TA-GVHD) has been reported in immunocompetent recipients of nonirradiated cellular blood components from donors who are homozygous for an HLA haplotype shared with the patient. In these cases, donor lymphocytes have no antigens foreign to the recipient, and this similarity in HLA antigens appears important for the development of TA-GVHD. Experience with 65 patients receiving apheresis platelets matched for class I HLA antigens was reviewed to determine the incidence of such a transfusion among HLA-matched, unrelated donor-recipient pairs. In 5 percent of transfusions (31/673), the patient received lymphocytes from a donor exhibiting no antigens foreign to the recipient, but the patient had additional HLA-A or -B antigens not present on donor lymphocytes. Twenty-three percent (n = 15) of patients received at least one such transfusion. In addition, most patients were immunosuppressed as a result of their underlying disease or therapy, which may decrease the degree of antigen matching required to initiate TA-GVHD. Until the pathogenesis of this disease is better understood, it is recommended that the transfusion of an HLA-matched cellular blood component be considered a risk factor for the development of TA-GVHD regardless of the patient's immune status, and that all such blood components be irradiated.
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PMID:Potential for transfusion-associated graft-versus-host disease due to apheresis platelets matched for HLA class I antigens. 787 25


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