Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among 42 consecutive recipients of unrelated marrow were 39 HLA-A, -B, -DR identical, matched unrelated donors (MUD) and three with one HLA antigen mismatch. The majority were genomically typed for DRB, DQA, DQB and DPB. The recipients of MUD marrow were compared with 39 recipients of marrow from HLA-identical siblings with similar diagnoses, disease status and age. Each group included 24 patients with hematological malignancies, 6 with severe aplastic anemia and 9 inherited disorders. Immunosuppression consisted of anti-thymocyte globulin (ATG; pre-BMT mainly to recipients of unrelated marrow), CsA and four doses of MTX. Grade I acute GVHD was treated with prednisolone 2 mg/kg. In a comparison of MUD marrow recipients and HLA-identical siblings 34 of 39 and 36 of 39 of the patients engrafted, respectively. Recipients of MUD marrow and HLA-identical siblings achieved 0.2 x 10(9) WBC/l on day 16 (median) and 14, respectively (P = 0.03). Furthermore, the recipients of MUD marrow needed more platelet transfusions (P = 0.04). The incidence of acute GVHD grade II-III was 15% in the MUD marrow recipients compared with 11% among the HLA-identical siblings. The 2-4 year cumulative incidence of chronic GVHD was 29% and 22% in the two groups, respectively. The overall 2-year survival was 59 and 78%, respectively. Among patients with CML in chronic phase or accelerated phase (n = 26), 2-year relapse-free survival was 79% in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Similar incidence of graft-versus-host disease using HLA-A, -B and -DR identical unrelated bone marrow donors as with HLA-identical siblings. 765 90

Current practice for the selection of unrelated donors involves serological typing of HLA-A, -B and -DR antigens, DNA analysis of the class II region and the MLR. However, even after matching for the class II loci at the DNA level, a significant proportion of matched unrelated pairs remain MLR reactive. Ideal matching for BMT would be a match for the whole MHC haplotype rather than individual HLA loci. In the present study, we have evaluated the complementary role of class III typing in determining MHC identity. A group of 86 donor/recipient pairs, of which 14 were unrelated, was investigated using C4, Bf, HSP70 and TNF DNA probes. Phenotypically HLA-matched siblings were always identical at the C4 locus which is the most polymorphic of all the loci examined. Nine of the 14 HLA serologically matched MLR non-reactive (RRI < 20%) unrelated pairs had class III mismatching. Four of these pairs with class III mismatching were matched at the DRB and DQB loci by RFLP analysis. These results demonstrate that serological identity, DRB/DQB RFLP-matching and a negative MLR do not always match the whole haplotype in unrelated pairs. It can be concluded that the linkage of the class III loci to both HLA regions makes this region a reliable marker of the whole MHC haplotype.
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PMID:MHC class III polymorphisms in selection of donors for BMT. 809 7

An important problem in the selection of unrelated donors for bone marrow transplantation (UD-BMT), is HLA matching, between selected donor and recipient. Serological screening, mixed lymphocyte culture (MLC), and sequence specific oligonucleotide genotyping (PCR-SSO) are the methods commonly used for typing of HLA-genes. These ways to select donor candidates are time-expensive. We set up new applications of the "fingerprinting-PCR" technique, to analyse the polymorphic second exon of DRB, DQB, DQA, DPB of HLA Class II and second exon A, B, C HLA-Class I genes, and to search for identity between patient and serologically selected unrelated donors. In an assessment of the technique, 50 normal samples, and 4 unrelated HLA-A and HLA-B serological matched patient-donor pairs were analysed for HLA polymorphic regions. In 3 of the 4 cases (UD-BMT) at least HLA-DRB mismatched different donor-transplanted patterns were identified. In all cases PCR-SSO analysis was performed as control. Based on our data, we suggest that identification of UD for allogeneic BMT should follow these steps: 1) serological HLA-Class I and II genes screening; 2) HLA-Class II DRB gene PCR fingerprinting; 3) confirmation by SSO analysis in case of fingerprinting identity. 4) HLA-Class II DQA, DQB, DPB PCR fingerprinting. Moreover, confirmation by PCR fingerprinting or protein isoelectrofocusing of HLA-Class I identity is recommended. This "strategy" may contribute to rapid and specific selection of unrelated marrow donors.
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PMID:New strategies for selection of unrelated bone marrow donors. 844 42

The selection of fully matched unrelated volunteer donors (UVD) in BMT requires a molecular characterization of MHC polymorphism, since most phenotypically HLA-identical donors can be non-identical when analyzed at a genomic level. The present report describes a molecular typing protocol for HLA genes developed for the selection of UVD, and its application to some donor-recipient pairs. The protocol involves three successive steps. Firstly, PCR with sequence-specific primers for HLA-DRB1 and -DQB1 genes is performed to identify the major alleles of the recipient. PCR-fingerprint matching is then introduced for HLA-A, B, C and DRB, DQB and DPB genes to screen prospective donors. Those showing matched fingerprinting patterns are finally submitted to direct sequencing of the DRB1 gene. DPB compatibility is assessed by oligotyping when there are several potential class I and DRB matched donors. This strategy was applied retrospectively to three BMT recipients and their previously selected donors. Three other patients and their 12 prospective donors were submitted to our protocol before BMT. Clinical evaluation of transplant outcomes indicates the primary importance of complete DRB and class I matching, while DQB and DPB compatibility seems to be less critical.
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PMID:Molecular analysis of HLA genes for the selection of unrelated bone marrow donor. 853 3

Despite the use of partially T cell-depleted grafts, 20% of the recipients of an HLA-identical sibling marrow graft develop aGVHD > or = II. This indicates that the current method for selecting a sibling donor, ie serological typing for HLA-A, B and DR, and a mixed lymphocyte culture (MLC) or molecular typing for HLA-DRB/DQB, is not predictive for aGVHD. In order to optimise our selection procedure, we retrospectively analysed patients who developed aGVHD > or = II by means of sequencing based typing for HLA-DPB and frequency analysis of alloreactive helper and cytotoxic T lymphocyte precursors (HTLp-f and CTLp-f). Patients who did not develop aGVHD or developed aGVHD grade I served as controls. Retrospective typing for HLA-DPB revealed only a single disparity in the group with aGVHD > or = II, indicating that mismatches for antigens other than HLA are the major cause of aGVHD in these patients. Furthermore, in our patient group, neither HTLp-f nor CTLp-f were predictive for development of aGVHD indicating that these assays in their current set-up are insufficiently sensitive to predict aGVHD in BMT with a partially T cell-depleted graft. We conclude, that HLA-identical siblings can be identified by means of serological typing for HLA-A and B and intermediate resolution molecular typing for DRB and DQB, but that for the prediction of aGVHD cellular tests with higher sensitivity and specificity as compared to the currently used HTLp-f and CTLp-f assays need to be developed.
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PMID:Helper and cytotoxic T cell precursor frequencies are not predictive for development of acute graft-versus-host disease after partially T cell-depleted HLA-identical sibling BMT. 987 66