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)

Since HLA-DP mismatches are known to induce proliferative response in MLR I, we investigated the real impact of the different DP alleles and the possible role of one or several hypervariable regions of the DPB allelic sequences. Accordingly, we performed MLR I between HLA-A, B, DR, DQ, and Dw identical individuals DP oligotyped after DNA amplification. A total of 23 one-DP-mismatched healthy stimulator and responder cells displaying nine different DP specificities were thus evaluated in 52 MLRs I. This allowed us to analyze the impact of amino acid composition of each of the six hypervariable regions independently of the amino acid matching or mismatching in the five others. We show here that DP combinations sharing the same amino acid sequence in the third (C) and fourth (D) hypervariable regions are associated with a low proliferative response in vitro (p less than 0.01). These data imply that a perfect HLA-DP matching may not be requisite in selecting bone marrow donors. Indeed, the choice of donors may rely on determination of these particular mismatched HVRs between the DP alleles involved especially in GvHD direction. This policy including prospective DP oligotyping should be of great interest, especially when MLRs I are false negative or nonevaluable. It will enable a better definition of which DP mismatches are acceptable in BMT.
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PMID:Crucial role of the third and fourth hypervariable regions of HLA-DPB1 allelic sequences in the mixed lymphocyte reaction. 153 19

In a study carried out for patients receiving intrafamilial HLA-A,B,DR identical, MLC negative bone marrow transplants, RFLP profiles of HLA-class II for 27 donor recipient pairs were analyzed. Twenty-four pairs were found HLA-class II identical while three pairs were HLA-DP incompatible. The patients of these three pairs did not reveal any acute GVHD greater than or equal to grade II. The seven cases of acute GVHD greater than or equal to grade II found in our panel were HLA-DR, DQ, and DP compatible. Thus, in practical terms pretransplantation HLA-DP typing does not seem necessary for intrafamilial HLA-identical, MLC negative BMT. On the other hand, this work confirmed that it is possible to type for HLA-DP using molecular biological techniques, and this in itself may have some important implications for unrelated BMT.
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PMID:HLA-DP genotyping in HLA-A,B, and DR identical intrafamilial bone marrow transplantation. 196 10

Possible donors may be recommended by the following order: 1. HLA-identical twins (syngeneic) 2. HLA-identical siblings 3. HLA-haploidentical related donors The increased number of additional HLA-incompatibilities (HLA-A, -B, -DR) increases the risk of GVHD. 4. HLA-phenoidentical and MLC-negative unrelated donors The DRS for BMT includes the early HLA typing of the patient and of all related potential donors, covering all known antigens. Evidence on the basis of MLC should be available for cellular non-reactivity between donor and recipient cells, although this will be rarely possible with haploidentical related donors. Donor-specific HLA antibodies must not be detectable in the recipient. No generally accepted method has so far become available for consideration of minor histocompatibility antigens in the context of DRS for BMT.
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PMID:Histocompatibility and bone marrow transplantation (BMT). 248 Feb 87

Six children (aged 9 months to 10 and 5/12 years) with hemophagocytic lymphohistiocytosis (HLH) have undergone allogeneic BMT in Sweden. In two of the children unrelated donors were used. Parents were available as donors in two of the cases and siblings in the other two. Conditioning before BMT consisted of etoposide, busulfan and cyclophosphamide with the addition of ATG in two cases and OKT 3 in one case. For post-transplant immunosuppression, i.v. methotrexate and cyclosporin A (CsA) were used in five cases, and in one child CsA was combined with methylprednisolone. Of the six children, four are alive and well 2 and 3/12 to 3 and 1/12 years after BMT. One child, who had an unrelated donor with one DR-antigen mismatch, died 30 days after BMT of fulminant grade IV GVHD. Another patients, seropositive for CMV, received marrow from an unrelated HLA-A, -B, -DR and -DP identical donor. After an initially uneventful course, CMV was isolated from her leukocytes. Seven months after BMT she developed a progressive obstructive chronic bronchiolitis and succumbed to respiratory insufficiency 14 months after the transplant. This study supports the view that BMT is the treatment of choice in HLH, particularly if an HLA-identical related donor is available.
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PMID:Allogeneic bone marrow transplantation for hemophagocytic lymphohistiocytosis in Sweden. 759 55

We performed a sequential study comparing two regimens, cyclosporine-methotrexate (CsA-MTX) and cyclosporine-methotrexate-methylprednisolone (CsA-MTX-MP) for graft-versus-host disease (GVHD) prophylaxis in patients undergoing matched unrelated donor bone marrow transplantation (MUD BMT). Study end-points were the development of GVHD, various infectious complications and survival. Twenty nine patients with malignant hematologic disease without HLA-compatible family donors were treated between May 1990 and November 1993. All donors were volunteers from the National Marrow Donor Program (NMDP) serologically HLA-A-A, B and DR identical. MLC reactivity and high resolution DR DNA typing were not used to exclude donors. Sixteen patients received CsA-MTX and 13 patients received CsA-MTX-MP. CsA and MTX doses were the same in both groups: CsA 1.5 mg/kg i.v. over 2h every 12h beginning the day prior to transplant (day-1) and MTX 10 mg/m2 i.v. bolus on days +1, +3 and +6 with leucovorin on days +2, +4 and +7. MP was administered at a dose of 0.25 mg/kg i.v. every 12h beginning on day +7 and increased to 0.5 mg/kg on day +14. Beginning on day +35 MP and CsA were tapered 5% per week with targeted discontinuation at 6 months. Both groups were comparable for primary disease, preparative regimen, recipient age (median 33 VS 33 years), donor age (median 39 vs 39.5 years), donor-recipient sex, donor ABO mismatch and serologic CMV positivity. All patients received similar supportive care.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Graft-versus-host-disease prophylaxis for matched unrelated donor bone marrow transplantation: comparison between cyclosporine-methotrexate and cyclosporine-methotrexate-methylprednisolone. 759 65

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

To prevent GVHD in BMT from unrelated donors, the matching of HLA between patient and donor is crucial. The appearance of acute GVHD was studied in 51 patients with hematological malignancies who were transplanted with non-T cell purged marrow from HLA-A,B and DR compatible unrelated donors with the assistance of the Tokai Marrow Donor Bank of Nagoya, Japan. Probability of grade II-IV acute GVHD was 32.0% and of grade III-IV acute GVHD was 17.0%. HLA-class II antigen compatibility showed a good correlation with the occurrence of acute GVHD. When the percentage relative response (RR) of MLC between patient and donor (GVHD vector) was < or = 5, grade II-IV acute GVHD was found in only 7.7% of patients (n = 16) and no severe grade III-IV GVHD occurred. Among patients with 6-10% RR (n = 10), 25.9% showed grade II-IV GVHD and 14.3% grade III-IV GVHD. Among patients with > or = 11% RR (n = 20), however, the incidence of grade II-IV acute GVHD reached 51.8% and that of grade III-IV acute GVHD 36.2%. These reactivities of MLC reflected the compatibility of HLA-DRB1 and DPB1. The fact that the incidence of acute GVHD in BMTs from HLA-A,B,DR compatible Japanese pairs was found to be lower than in the USA may be due to less diversity of the genetic background in Japan.
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PMID:Low incidence of acute GVHD in patients transplanted with marrow from HLA-A,B,DR-compatible unrelated donors among Japanese. 777 12

We studied 23 consecutive patients, median age 34 years, with relapsed or resistant aggressive lymphoma who underwent allogeneic BMT at the UCLA Medical Center Bone Marrow Transplantation Unit from 1 November 1984 to 30 March 1993. All patients were < 50 years of age and had sibling donors who were matched at the HLA-A, B and DR loci. Nine patients had Hodgkin's disease (HD) and 14 had non-Hodgkin's lymphoma (NHL); three of these had low grade histology and 11 had intermediate or high grade lymphoma histology. After a median follow-up of 34 months, eight patients are alive, seven without recurrent lymphoma. Five patients had early deaths. The disease-free survival for the entire group is 26% with an overall survival of 29%. There was no difference in survival rate on the basis of disease or histology. Comparing preparative regimens containing TBI to those without there was no difference in survival rate (P = 0.35). Neither age nor sex was a significant determinant of outcome (P = 0.63 and 0.36, respectively). Disease status at the time of transplantation proved to be the important determinant of outcome. Patients transplanted with chemotherapy sensitive disease (n = 9), defined as a partial or complete response to salvage chemotherapy, had a survival rate of 42%, which was significantly better than those who had refractory disease at transplantation (n = 14), who had a survival rate of 21% (P = 0.006). However, this small, but significant fraction of patients with refractory disease was curable. Thus, our data demonstrate that allogeneic bone marrow transplantation is an effective means of treatment for relapsed or aggressive Hodgkin's and non-Hodgkin's lymphoma.
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PMID:Allogeneic bone marrow transplantation for Hodgkin's and non-Hodgkin's lymphoma. 777 22

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

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


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