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)

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.
 ...
PMID:Low incidence of acute GVHD in patients transplanted with marrow from HLA-A,B,DR-compatible unrelated donors among Japanese. 777 12

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.
 ...
PMID:Molecular analysis of HLA genes for the selection of unrelated bone marrow donor. 853 3

Recipients of marrow from alternative donors (unrelated or HLA-mismatched related donors) have a higher incidence of post-transplant complications compared to recipients of marrow from HLA-identical siblings. HLA disparity undetected by routine typing techniques has been suggested as one cause for the increased complications observed. Limiting dilution analysis (LDA) of donor-derived, host-reactive T cell precursor frequency prior to transplant has been proposed as a surrogate indicator of underlying HLA disparity which might be used to predict transplant outcome and aid in donor selection. We compared results of LDA of host-reactive IL-2 producing helper T lymphocytes (HTLp) and/or cytolytic T lymphocytes (CTLp) in 77 alternative marrow donor/recipient pairs with transplant outcome using univariate and multivariate analysis. All donor grafts were depleted ex vivo of mature T cells. Median patient age was 15 years (1-53). Donor selection was based on serologic typing for HLA class I and high resolution oligotyping for HLA-DRB1-DRB5, and HLA-DQB1. HLA-A and HLA-B locus antigens were retrospectively defined by one dimensional isoelectric focusing (IEF). Cox proportional hazards regression models were used to assess the impact of frequency and estimated cell dose of CTLp and HTLp on outcome. The CTLp assay was most sensitive to HLA-A and HLA-B locus disparity detected by serology or IEF. The HTLp assay detected class I disparity but was most strongly reactive in the presence of HLA-DRB1 disparity. Univariate analysis indicated a significant association of CTLp frequency and dose with severe (grades 3-4) acute graft-versus-host disease (GVHD), and of CTLp dose with chronic GVHD. Both assays were associated with survival and neither assay was associated with relapse. After adjustment for other significant covariables including known HLA disparity, the association of CTLp with acute GVHD was lost, however, CTLp frequency and CTLp dose remained associated with survival and HTLp frequency was associated with chronic GVHD. These data support the hypothesis that post-BMT complications may be influenced not only by T cell dose but by the alloreactive potential of the cells infused. LDA of alloreactive potential was useful in detecting disparity and in predicting survival or chronic GVHD in recipients of alternative donor TCD marrow grafts.
 ...
PMID:Association of donor-derived host-reactive cytolytic and helper T cells with outcome following alternative donor T cell-depleted bone marrow transplantation. 916 44

We have retrospectively analyzed the impact of prognostic factors on the outcome of serologically HLA-matched unrelated donor (UD) BMT for CML. For this purpose, we have studied a cohort of 366 patients transplanted in Europe between January 1985 and December 1994. The median age of the 211 males and 155 females was 34 years; 238 patients were transplanted in first chronic phase and 116 in advanced phases. The median interval from diagnosis to BMT was 827 days. GVHD prophylaxis consisted of CsA and MTX in 202 patients or of ex vivo or in vivo T cell depletion (TCD) in 129. Recently, DNA-based methods of HLA-class II typing have been used to improve donor selection. We obtained complete data on 300 donor/recipient (D/R) pairs. Among them, we have identified three groups of patients, according to specific HLA-DRB1 D/R compatibility. Two hundred and ten patients received marrow from donors identical for HLA-DRB1 (group 1). Thirty-one patients received BMT from a donor who was HLA-DRB1 mismatched (group 2) and 59 from a donor in whom specific HLA-DRB1 typing was not performed (group 3). The overall survival was 37 +/- 3% at 2 years and leukemia-free survival (LFS) was 31 +/- 3%. In univariate analysis, five variables had a favorable effect on LFS: transplant in first chronic phase (P = 0.0001), time interval from diagnosis to BMT shorter than the median (P = 0.01), prophylaxis of GVHD without TCD (P + 0.001), acute GVHD < grade III (P = 0.0009) and HLA-DRB1 D/R matching (P = 0.0001). Transplant-related mortality (TRM) was 49 +/- 4% in group 1, 79 +/- 8% in group 2 and 80 +/- 6% in group 3 (P = 0.0001). Multivariate analysis confirmed that HLA-DRB1 matching was the most significant factor influencing survival (P = 0.04), LFS (P = 0.013) and TRM (P = 0.0049). From these results, we have defined a 'good risk' group, ie patients transplanted in first chronic phase, from an HLA-DRB1 matched donor, without TCD as prophylaxis against GVHD. The 2 year LFS, TRM and relapse incidence for this group were 51 +/- 5%, 47 +/- 5% and 2 +/- 2%, respectively. This suggests that the long-term outcome of patients with favorable prognostic features can approach that of patients transplanted from geno-identical siblings. In contrast, the TRM for patients transplanted for advanced disease from non HLA-DRB1-identical donors was 94%. Such a high TRM clearly indicates that UD BMT is not justifiable for these individuals.
 ...
PMID:European results of matched unrelated donor bone marrow transplantation for chronic myeloid leukemia. Impact of HLA class II matching. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. 923 50

In Vietnam, the first three cases of Allo-BMT were successfully performed in 1995 at the Blood Transfusion and Hematology Hospital (BT-H) of Ho Chi Minh City. Donors were HLA fully matched siblings (HLA-A, HLA-B and HLA-DRB1). The patients were a 26-year-old man with CML in chronic phase (CP), a 12-year-old woman with beta-thalassemia/Hb E and a 9-year-old girl with beta-thalassemia/Hb E. All patients were engrafted with the median time to recover ANC>0.5 x 10(9)/l, and platelet count >20 x 10(9)/l was 16 and 38 days. At 12 years after transplantation, all three patients are alive and well. Today, Vietnam has five SCT centers; in the north, there are three centers: 108 Military Hospital, Pediatric Institute and Blood transfusion and Hematology Institute; in the middle of Vietnam is Hue Hospital and in the south, the BT-H Hospital of Ho Chi Minh City. Until now, 65 patients have had SCT in Vietnam; among them, 52 patients had SCT at the BT-H Hospital, Ho Chi Minh City. Because of no connection of data between different SCT centers, we present here only the results performed at the BT-H Hospital, Ho Chi Minh City. With Allo-SCT we performed 19 cases with 3 procedures: BMT (4 cases), PBSC (6 cases) and cord blood transplantation (9 cases); patients were diagnosed with AML (n=7), ALL (n=1), CML (n=5) and beta-thalassemia (n=6). Following transplantation, 7 patients (36.84%) relapsed, 12 (63.16%) remained alive and overall survival times: 6.81+/-1.35 years, disease-free survival times: 6.69+/-1.4 years (range 0.5-12 years). With Auto-SCT: since November 1996, we have performed 33 cases of autologous PBSC transplantation consisting of without cryopreservation (24 cases) and with cryopreservation (9 cases); patients were diagnosed with AML in CR1 (n=21), ALL in CR1 (n=6), CML in CP (n=5) and non-Hodgkin's lymphoma in CR1 (n=1). The median age of the patients was 35 years (range 18-46). The median time to recover ANC >0.5 x 10(9)/l and platelet count >20 x 10(9)/l was 14 days (range 9-25 days) and 35 days (range 9-120 days). Following transplantation, 18 patients (54.50%) relapsed, 15 (45.45%) remained alive and overall survival times: 5.74+/-0.82 years and disease-free survival times: 5.48+/-0.92 years. There was no statistically significant difference of overall survival and disease-free survival between Allo-SCT and Auto-SCT procedures (P>0.05). These preliminary data suggest that HSCTs have been used as one of the standard treatments for hematological diseases and malignancies in Vietnam and that cord blood is an alternative source of hematopoietic stem cells for allogeneic transplantation in children.
 ...
PMID:Current status of hematopoietic stem cell transplantations in Vietnam. 1872 91

Bone marrow transplantation from unrelated donors (UR-BMT) has been considered to be effective for patients with hematological malignancies who have no suitable related donor. However, disparities of HLA between a recipient and a donor increase the risk of severe acute graft-versus-host disease (GVHD). We evaluated GVHD prophylaxis using tacrolimus and methotrexate for HLA-A, B, or DRB1 genotypically mismatched UR-BMT. Fifty-five patients were enrolled in this study. The incidence of grade III to IV acute GVHD was 23.6% for all patients. No significant difference in the incidence of grade III to IV acute GVHD was observed between HLA-A or B 1 locus mismatch transplantation (18.8%) and HLA-DRB1 1 locus mismatch transplantation (16.7%) (P = 0.96). The incidence of chronic GVHD was 71.7%. Disease-free survival at 5 years was 53.2% for patients with standard risk disease and 24.5% for patients with high-risk disease. Patients with chronic GVHD exhibited better disease-free survival than those without chronic GVHD (53.2 vs. 30.9%, P = 0.011). Twenty patients (36.4%) had a relapse of leukemia and 14 of them died of recurrent leukemia. This study indicates tacrolimus and methotrexate can lower the risk of severe acute GVHD after HLA-A, B, or DRB1 genotypically 1 locus mismatched UR-BMT.
 ...
PMID:Phase II study of tacrolimus and methotrexate for prophylaxis of acute graft-versus-host disease after HLA-A, B, and DRB1 genotypically mismatched unrelated bone marrow transplantation among Japanese patients. 1905 93