UMLS:C0018133 - FACTA Search

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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)

From June 1998 to July 2004, Guangzhou umbilical cord blood bank provided unrelated umbilical cord blood for 54 patients to more than 21 transplantation centers. HLA sequencing-based typing (SBT) was used to re-analyze the results of HLA antigens and alleles so as to investigate the relationship between HLA alleles and GVHD. The information about 48 out of 54 patients was obtained after 6 months of follow up. SBT was used to identify HLA-A, B, DRB1 alleles in 48 patients received the unrelated umbilical cord blood units, and the obtained results were compared with the results of HLA-SSP Low Resolution Typing. The results showed that the difference of GVHD incidence between less than 2 mismatched HLA sites and less than 3 sites was statistically significant (P < 0.05). In the results from single factor analysis and high-resolution typing of HLA-A, B and DRB1 alleles, the mismatch between HLA-B and HLA-DRB1 alleles was found to be a significant factor for the occurence of GVHD. It is concluded that SBT plays an important role in umbilical cord blood transplantation, and the incidence of GVHD is higher in the transplantation with HLA-DRB1 alleles mismatching.
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PMID:[Clinical application of HLA sequencing in unrelated umbilical cord blood transplantation]. 1709 93

The National Marrow Donor Program maintains a registry of volunteer donors for patients in need of a hematopoietic stem cell transplantation. Strategies for selecting a partially HLA-mismatched donor vary when a full match cannot be identified. Some transplantation centers limit the selection of mismatched donors to those sharing mismatched antigens within HLA-A and HLA-B cross-reactive groups (CREGs). To assess whether an HLA mismatch within a CREG group ("minor") may result in better outcome than a mismatch outside CREG groups ("major"), we analyzed validated outcomes data from 2709 bone marrow and peripheral blood stem cell transplantations. Three-hundred and ninety-six pairs (15%) were HLA-DRB1 allele matched but had an antigen-level mismatch at HLA-A or HLA-B. Univariate and multivariate analyses of engraftment, graft-versus-host disease, and survival showed that outcome is not significantly different between minor and major mismatches (P = .47, from the log-rank test for Kaplan-Meier survival). However, HLA-A, HLA-B, and HLA-DRB1 allele-matched cases had significantly better outcome than mismatched cases (P < .001). For patients without an HLA match, the selection of a CREG-compatible donor as tested does not improve outcome.
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PMID:HLA mismatching within or outside of cross-reactive groups (CREGs) is associated with similar outcomes after unrelated hematopoietic stem cell transplantation. 1720 13

We investigated the effect of multiple-unit umbilical cord blood (UCB) transplantation on engraftment in the setting of severe human leukocyte antigen (HLA) mismatch. Ten poor-risk adult patients with hematological malignancy received multiple unit, HLA-unmatched, sex-mismatched, unrelated UCB transplantation after a reduced intensity-conditioning regimen (RICR) with engraftment as the primary endpoint. The median age of the patients was 55 years with a range of 28-67. Patients received one unit of UCB per 10 kg of recipient body weight (5-7 units). The median number of nucleated cells and CD34(+) cells per kilogram of recipient body weight infused was 6.3 x 10(7) (range 3.8-10.0) (NC/kg) and 5.7 x 10(5) (range 1.1-11.9) (CD34/kg), respectively. Three patients expired before day 28 and were not evaluable for engraftment. Five of the remaining 7 patients showed increasing neutrophil counts. Fluorescent in situ hybridization (FISH) for the Y chromosome or HLA-typing showed only donor cells in the peripheral blood. After engraftment, HLA typing was done on 3 patients and their infused UCB units. All revealed the presence of a single HLA type concordant with one of the infused units. Moreover, the order of infusion did not influence which UCB unit engrafted. The engrafting UCB units were infused first or second in one case and fourth in the other two. One patient transplanted for refractory acute lymphoblastic leukemia (ALL) survives in continuous complete remission 4 years after transplant. He engrafted with one UCB unit, is fully hematologically reconstituted, has no evidence of graft-versus-host disease (GVHD), and takes no immunosuppressive medication. HLA typing reveals that the recipient and the engrafted cord blood match at only one HLA-B locus using conventional 6 antigen typing (A, B, and DR). Although engraftment was not accelerated, it did occur in the majority of evaluable patients. Long-term disease-free survivorship without debilitating GVHD is possible in patients with refractory hematological malignancy who receive unmatched multiple unit UCB.
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PMID:Multiple unit HLA-unmatched sex-mismatched umbilical cord blood transplantation for advanced hematological malignancy. 1734 13

Treating patients with severe aplastic anemia (SAA) who fail to respond to immunosuppressive therapy (IST) and do not have an HLA-matched donor is challenging. We report favorable outcomes in 11 patients who underwent bone marrow transplantation (BMT) from an HLA-mismatched unrelated donor. The median age was 11 years (range, 3-20 years). The conditioning regimen consisted of cyclophosphamide (200 mg/kg), antithymocyte globulin (10 mg/kg), and total body irradiation (5 Gy). Patients received tacrolimus and methotrexate for prophylaxis against graft-versus-host disease (GVHD). Donorrecipient pairs were mismatched for the HLA-DR antigen in 8 patients by serologic typing. HLA-A and HLA-B antigens were mismatched in 1 and 2 patients, respectively. Ten patients achieved engraftment. One patient who failed to engraft was rescued by a second transplantation from her mother, who was mismatched at 2 HLA antigens. Acute GVHD of grades II to IV occurred in 2 patients. Three patients developed limited chronic GVHD, and 1 patient developed extensive chronic GVHD of the lung. All patients are alive at 9 to 56 months after transplantation (median, 33 months). Considering our encouraging results, HLA-mismatched unrelated-donor BMT for SAA is feasible as a salvage therapy for nonresponders to IST.
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PMID:Feasibility and results of bone marrow transplantation from an HLA-mismatched unrelated donor for children and young adults with acquired severe aplastic anemia. 1756 22

Hematopoietic cell transplantation (HCT) from an HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele-matched unrelated donor is a well-recognized life-saving treatment modality for patients with hematologic disorders. The morbidity and mortality from clinically significant acute graft-versus-host disease (aGVHD) remains a limitation. The extent to which transplantation outcome may be improved with donor matching for HLA-DP is not well defined. The risks of aGVHD, relapse, and mortality associated with HLA-DPB1 allele mismatching were determined in 5929 patients who received a myeloablative HCT from an HLA-A-, HLA-B-, HLA-C-, HLA-DRB1-, and HLA-DQB1-matched or -mismatched donor. There was a statistically significantly higher risk of both grades 2 to 4 aGVHD (odds ratio [OR] = 1.33; P < .001) and grades 3 to 4 aGVHD (OR = 1.26; P < .001) after HCT from an HLA-DPB1-mismatched donor compared with a matched donor. The increased risk of aGVHD was accompanied by a statistically significantly decrease in disease relapse (hazard ratio [HR] = 0.82; P = .01). HLA-DPB1 functions as a classical transplantation antigen. The increased risk of GVHD associated with HLA-DPB1 mismatching is accompanied by a lower risk of relapse. Knowledge of the DPB1 matching status prior to transplantation will aid in more precise risk stratification for the individual patient.
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PMID:The importance of HLA-DPB1 in unrelated donor hematopoietic cell transplantation. 1772 64

Acute graft-versus-host disease (GVHD) is a rare complication of pancreas transplantation. We describe a 54-year-old male with type 1 diabetes who received a zero-antigen mismatched pancreas-after-kidney transplant from a pancreas donor who was homozygous at the HLA-B, -Cw, -DR, and -DQ alleles. Starting on postoperative day (POD) #22, the patient developed persistent fevers. Workup was notable only for low-grade cytomegalovirus viremia, which was treated. The fevers eventually disappeared. On POD #106, the patient was noted to have a diffuse erythematous rash. A skin biopsy was consistent with GVHD. Short tandem repeat DNA analysis of both peripheral blood lymphocytes and skin demonstrated mixed chimerism, confirming the diagnosis of GHVD. Soon after diagnosis, the patient developed pancytopenia and fevers and died of multiorgan failure on POD #145. Transplant clinicians should consider GVHD as a possible, although admittedly rare, cause of fevers of unknown origin in recipients of pancreas transplants.
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PMID:Fatal graft-versus-host disease presenting as fever of unknown origin in a pancreas-after-kidney transplant recipient. 1829 53

The aim was to evaluate two transplant strategies for patients who lack HLA-identical donors, namely HLA-A, HLA-B or -DR beta 1 mismatched unrelated donor (MM URD) transplants (n=14) and umbilical cord blood transplants (UCB, n=27). Diagnosis, disease stage and age were similar in the two groups. Cell dose was lower in the UCB group (P<0.001). Median time to ANC of >0.5 x 10(9)/l was 30 days in the UCB group and 17 days in the MM URD group (P=0.002). Engraftment of plt was delayed in the UCB group (P=0.03). The UCB patients required fewer erythrocyte transfusions (P=0.001). At 100 days, complete donor chimerism for CD3 was 63 and 44% in the UCB and MM URD groups, respectively. Acute GVHD of grades II-IV were 30% in the UCB group and 21% in the MM URD group. The corresponding figures for chronic GVHD were 9 and 20%, respectively. TRM was 30% in the UCB patients and 50% in the MM URD patients. Three-year survival was 66% in the UCB group and 14% in the MM URD group (P=0.006). Although the material is small and heterogeneous, engraftment was delayed, leukocyte chimerism was not significantly different and survival was superior using UCB rather than MM URD transplants.
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PMID:Unrelated cord blood and mismatched unrelated volunteer donor transplants, two alternatives in patients who lack an HLA-identical donor. 1876 60

HLA disparity between hematopoietic stem cell donors and recipients is one of the most important factors influencing transplant outcomes, but there are no well-accepted guidelines to aid in selecting the optimal donor among several HLA mismatched donors. In this report, HLA-A is used as a model to illustrate factors that are barriers to delineating the relationship between specific HLA mismatches and transplant outcomes in the United States. Patients in this investigation received transplants for hematologic malignancies that were facilitated by the National Marrow Donor Program (NMDP) between 1990 and 2002 (n = 4226). High-resolution HLA typing was performed for HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPA1, and -DPB1. HLA-A mismatches were observed in 745 donor-recipient pairs and 62% of these pairs also had disparities at HLA-B, -C, and/or -DRB1. The HLA-A mismatches involved 190 different combinations of HLA-A alleles and 51% of these were observed in only 1 pair. Addition of a single HLA-A disparity when HLA-B, -C, and -DRB1 were matched (n = 282) was associated with increased mortality (odds ratio [OR] = 1.32, confidence interval [CI] 1.07-1.63). When HLA-B, -C, and -DRB1 were matched, the most frequent HLA-A mismatches were HLA-A*0201:0205 (n = 28), HLA-A *0301:0302 (n = 15), HLA-A *0201:0206 (n = 15), HLA-A *0201:6801 (n = 12), HLA-A*0101:1101 (n = 11), and HLA-A*0101:0201 (n = 10). There were no statistically significant relationships between any of these disparities and transplant outcomes (engraftment, acute and chronic graft-versus-host disease [aGVHD, cGVHD] relapse, treatment-related mortality [TRM], or overall survival [OS]) when adjustments for multiple comparisons were considered. Achieving 80% power to detect an effect of any 1 of these 6 HLA-A disparities on survival is estimated to require a total transplant population of 11,000 to more than 1 million U.S. donor-recipient pairs depending upon the HLA disparity. Thus, alternative approaches are required to develop a clinically relevant ranking system for specific HLA disparities in the United States.
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PMID:HLA-A disparities illustrate challenges for ranking the impact of HLA mismatches on bone marrow transplant outcomes in the United States. 1958 87

The polymorphic products of major histocompatibility complex class I-related chain A (MICA) genes are important in solid organ transplantation rejection. MICA expression is limited to gut epithelium and may play a role in triggering acute graft-versus-host disease (aGVHD). A total of 236 recipients of unrelated donor transplantation were studied. Donor-recipient human leukocyte antigen (HLA) match was 10/10 human leukocyte antigen (HLA-A, -B, -C, -DRB1, -DQB1) in 73% and MICA mismatch in 8.4%. Because of physical vicinity of the loci, MICA mismatch was significantly associated with mismatch at HLA-B and HLA-C. A higher rate of grade II-IV aGVHD was seen in MICA-mismatched patients (80% vs 40%, P = .003) irrespective of degree of HLA matching (HLA 10/10 match: 75% vs 39%, P = .02) and HLA any mismatch (83% vs 46%, P = .003). The rate of grade II-IV gastrointestinal aGVHD was also higher in MICA-mismatched patients (35% vs 17%, P = .05). We conclude that MICA may represent novel a transplantation antigen recognized by human allogeneic T cells. This study was registered at ClinicalTrials.gov (Identifier NCT00506922).
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PMID:Donor-recipient mismatches in MHC class I chain-related gene A in unrelated donor transplantation lead to increased incidence of acute graft-versus-host disease. 1996 15

In fully HLA-matched allogeneic hematopoietic cell transplantation (HCT), the main mechanism of the beneficial graft-versus-tumor (GVT) effect and of detrimental graft-versus-host disease (GVHD) is believed to be caused by donor cytotoxic T cells directed against disparate recipient minor histocompatibility antigens (miHAs). The most common origin of disparate miHAs is nonsynonymous single nucleotide polymorphism (nsSNP) differences between donors and patients. To date, only some 30 miHAs have been identified and registered, but considering the many different HLA types in the human population, as well as all the possible nsSNP differences between any 2 individuals, it is likely that many miHAs have yet to be discovered. The objective of the current study was to predict novel HLA-A- and HLA-B-restricted miHAs in a cohort of patients treated with nonmyeloablative conditioning allogeneic HCT (matched related donor, n = 70; matched unrelated donor, n = 56) for a hematologic malignancy. Initially, the cohort was genotyped for 53 nsSNPs in 11 known miHA source proteins. Twenty-three nsSNPs within 6 miHA source proteins showed variation in the graft-versus-host (GVH) direction. No correlation between the number of disparate nsSNPs and clinical outcome was seen. Next, miHAs in the GVH direction were predicted for each patient-donor pair. Using the NetMHCpan predictor, we identified peptides encompassing an nsSNP variant uniquely expressed by the patient and with predicted binding to any of the HLA-A or -B molecules expressed by the patient and donor. Patients with more than the median of 3 predicted miHAs had a significantly lower 5-year overall survival (42% vs 70%, P = .0060; adjusted hazard ratio [HR], 2.6, P = .0047) and significantly higher treatment-related mortality (39% vs 10%, P = .0094; adjusted HR, 4.6, P = .0038). No association between the number of predicted miHAs and any other clinical outcome parameters was observed. Collectively, our data suggest that the clinical outcome of HCT is affected not by disparate nsSNPs per se, but rather by the HLA-restricted presentation and recognition of peptides encompassing these. Our data also suggest that 6 of the 11 proteins included in the current study could contain more miHAs yet to be identified, and that the presence of multiple miHAs confers a higher risk of mortality after nonmyeloablative conditioning HCT. Furthermore, our data suggest a possible role for in silico based miHA predictions in donor selection as well as in selecting candidate miHAs for further evaluation in in vitro and in vivo experiments.
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PMID:Degree of predicted minor histocompatibility antigen mismatch correlates with poorer clinical outcomes in nonmyeloablative allogeneic hematopoietic cell transplantation. 2035 33

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