Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.1.1.69 (BMT)
2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Twenty eight Hungarian patients lacking a compatible related donor and their 61 HLA-A,B,DR serologically identical potential unrelated donors (selected from BMDW) were investigated in this study. Out of the 61 donor-recipient pairs only 7 (11,5%) proved to be HLA-identical at DNA level. Thirty one pairs (50,8%) differed in DP alleles, 1 pair (1,6%) has a DQ mismatch only and 22 (36,1%) pairs differed in more alleles. More than one potential donor was found for 26 patients and 5 of them have several donors with DP mismatches only. Among the 31 donor-recipient pairs differing only in DP alleles, 0, 1 and 2 mismatches were observed in GvH direction in 7, 10 and 14 cases, respectively. In the MLC assay no proliferative response was observed when no DP mismatch has been found. Among the 1 and 2 DP mismatched cases 11 (35,5%) gave negative and 13 (41,9%) gave positive MLR results. We have found a large scatter in RR values. On the basis of the DNA typing and MLR results we have found that HLA-DPB1*0101-0201 stimulator-responder combination always gave negative MLR in both direction. HLA-DPB1*0201-0301 and DPB1*0301-0401 allele combinations were reactive in all cases. In conclusion MLC assay might indicate the low immunogeneicity in certain DP allele combinations as well as the avoidable positive combinations, which may help to select the best fitting donor for BMT.
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PMID:Influence of HLA-DPB1 mismatches on MLR responses: the role of high resolution HLA class II typing and MLC in unrelated donor selection for BMT. 991 30

To evaluate the outcomes of unrelated bone marrow transplantation facilitated by TCTMDR, we focused on 48 marrow transplants performed in Taiwan during the period May 1994 to June 1997. Follow-up of these 48 cases was made up to 30 May 1998. The average length of follow-up was 328 days (range 7-1385 days). All the donor/recipient pairs were HLA-A, B and DR matched and were divided into two risk groups based on diagnosis and stage of disease. There were 24 standard risk and 24 high risk patients. Engraftment occurred in 40 patients (83.3%). Acute and chronic GVHD was observed in 80% of evaluable patients and accounts for 41% of deaths. The second leading cause of death was infection, accounting for 35% of deaths. The overall probability of survival for the 48 patients after BMT over 2 years was 33.3% (95% CI 19.67-46.32%). The probability of survival for standard risk and high risk groups was 54% and 8%, respectively. In multivariate analysis, patients who were younger, in the standard risk group, or with a shorter search interval showed a higher survival probability.
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PMID:Marrow donor registry and bone marrow transplantation from unrelated donors in Taiwan: initial experience of the Tzu Chi Taiwan Marrow Donor Registry (TCTMDR). 1021 51

In December 1991, the Japan Marrow Donor Program (JMDP) was established with the cooperation of the Japanese Red Cross and Japan Marrow Donor Foundation under the auspices of the Ministry of Health and Welfare in Japan. By December 1998, 122365 HLA-A,B typed volunteer marrow donors and 7207 patients had been cumulatively registered in the JMDP. The results of HLA-matching between donors and patients revealed that 5684 out of 7207 (78.9%) patients could have at least one HLA-A,B,DR serologically matched donor. Among these matched pairs, 1829 unrelated bone marrow transplants (UR-BMT) were performed. The initial 500 UR-BMT transplanted from January 1993 to October 1995 were analyzed as of July 1998. Engraftment was achieved in 95% of cases. Probability of the occurrence of grade III and IV acute GVHD was 18.4%. The rate of disease-free survival (DFS) of the patients who had standard-risk leukemia and did not suffer from grade III or IV acute GVHD (n = 154) was 60-71% and the rate of survival of patients with aplastic anemia was 56%. It can be stated that UR-BMT is a modality of treatment which is as effective as related BMT if the occurrence of grade III or IV acute GVHD is predicted and prevented.
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PMID:Analysis of 500 bone marrow transplants from unrelated donors (UR-BMT) facilitated by the Japan Marrow Donor Program: confirmation of UR-BMT as a standard therapy for patients with leukemia and aplastic anemia. 1055 59

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disease of hematopoiesis due to a mutation in the PIG-A gene. Affected patients may demonstrate hemolysis or venous thrombosis, and may develop MDS or aplastic anemia. Successful results may be obtained after conditioning and transplantation from syngeneic or genotypically matched sibling donors. Experience with transplantation from matched unrelated donors (MUD) is limited to eight patients, with only one survivor. We report three patients who underwent successful MUD BMT for PNH. All three patients had severe aplastic anemia (SAA) and PNH at the time of BMT. Unrelated donors were six-antigen HLA-matched (n = 2) or HLA-A mismatched (n = 1). Conditioning consisted of cytarabine, cyclophosphamide, TBI, and ATG. Grafts were T cell-depleted by anti-CD6/CD8 antibodies + complement. Further GVHD prophylaxis consisted of cyclosporine. Patients received 0.7-1.1 x 10(8) nucleated cells/kg and 1.1-2.1 x 10(6) CD34(+) cells/kg. Neutrophil engraftment occurred at 16-21 days. One patient developed grade 1 acute GVHD. Although all three patients experienced significant transplant-related complications, they ultimately resolved and all patients are alive and well 30-62 months after BMT. T cell-depleted MUD BMT is an effective treatment option for PNH-related MDS and SAA.
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PMID:Successful unrelated donor bone marrow transplantation for paroxysmal nocturnal hemoglobinuria. 1131 87

We report a case of Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD) after allogeneic bone marrow transplantation (allo-BMT) from a partially mismatched related donor for acute lymphocytic leukemia, which was treated successfully by donor lymphocyte infusion (DLI). A 54-year-old woman in first complete remission from acute lymphocytic leukemia received an unmanipulated bone marrow transplant from an HLA-A 1-locus-mismatched sibling donor after preconditioning with cyclophosphamide and total body irradiation. Prophylaxis against graft-versus-host disease (GVHD) was done with tacrolimus and short-term methotrexate. Skin GVHD (grade I) occurred on day 36, but this subsided spontaneously without treatment. On day 61, rapidly progressive cervical lymphadenopathy with fever developed. Lymph node biopsy revealed lymphoid cell proliferation, which was positive for LCA, L26 and LMP-1. A diagnosis of EBV-LPD was made. After withdrawal of the tacrolimus, DLI (1 x 10(6) CD3 cells/kg) resulted in remission. This case suggests that even in the absence of risk factors such as severe GVHD, intensive immunosuppressive therapy and ATG administration, allo-BMT from an HLA 1-locus-mismatched related donor can be complicated by EBV-LPD, and that reduction of immunosuppressive therapy and DLI can be an effective treatment for it.
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PMID:[Successful donor lymphocyte infusion for Epstein-Barr virus-associated lymphoproliferative disorder after allogeneic bone marrow transplantation from an HLA 1-locus-mismatched sibling donor in a patient with acute lymphocytic leukemia]. 1180 79

In order to determine the influence of HA-1 minor histocompatibility antigen mismatch on BMT outcome, we analyzed a pool of 94 thalassemic transplanted patients all selected for the presence of HLA-A(*)0201 allele. The HA-1 typing was performed using SSP analysis. All the patients received bone marrow from HLA-identical MLC nonresponsive siblings. As graft-versus-host-disease (GVHD) prophylaxis, all patients received cyclosporin and short methotrexate. Grades II-IV GVHD occurred in five (33.3%) of the 15 patients with recipient HA-1 disparity compared with 14 (17.7%) of the 79 patients without HA-1 disparity. Despite the higher incidence of acute graft-versus-host-disease (aGVHD) in the group of patients with HA-1 incompatibility, these data were not statistically significant. However, it was interesting to observe that no GVHD developed in any of the 15 cases in which the recipient was HA-1 negative and the donor HA-1 positive.
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PMID:Recipient mHag-HA1 disparity and aGVHD in thalassemic-transplanted patients. 1269 24

Graft failure and nonrelapse mortality (NRM) are major obstacles after the first unrelated-donor bone marrow transplantation (UD-BMT) with reduced-intensity conditioning. We evaluated UD-BMT with fludarabine (5 x 25 mg/m2) and melphalan (2 x 90 mg/m2) treatment combined with short-term methotrexate and tacrolimus (n = 20) or cyclosporine (n = 2) therapy for 22 patients with hematologic malignancies who were ineligible for conventional conditioning. Only 9 patients were in remission at transplantation. Seventeen patients underwent HLA-matched or DRB1 allele-mismatched transplantation, and 5 patients underwent HLA-A allele-mismatched or serologically HLA-DR-mismatched transplantation. Regimen-related toxicities were tolerable, although transient oral mucositis, hepatobiliary enzyme elevation, and diarrhea were observed frequently. All evaluable patients achieved sustained neutrophil engraftment, and all patients tested showed complete donor chimerism on day 28. With a median follow-up of 16 months, NRM and overall survival rates at 1 year were 19% and 81%, respectively, among the patients who underwent HLA-matched or DRB1 allele-mismatched transplantation. Acute graft-versus-host disease (GVHD) of grades II to IV occurred in 26% of the patients. The cumulative incidence of chronic GVHD was 44%. Despite the small number of patients and the short follow-up period, this reduced-intensity regimen enabled satisfactory engraftment and achievement of rapid complete donor chimerism with tolerable toxicities in the patients, including those who underwent HLA-mismatched UD-BMT.
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PMID:Stable engraftment after a conditioning regimen with fludarabine and melphalan for bone marrow transplantation from an unrelated donor. 1675 39

The responsible human leukocyte antigen (HLA) locus and the role of killer immunoglobulin-like receptor (KIR) ligand matching on transplantation outcome were simultaneously identified by multivariate analysis in 1790 patients with leukemia who underwent transplantation with T-cell-replete marrow from an unrelated donor (UR-BMT) through the Japan Marrow Donor Program. The graft-versus-leukemia (GVL) effect depended on leukemia cell type. HLA-C mismatch reduced the relapse rate in acute lymphoblastic leukemia (ALL) (hazard ratio [HR] = 0.47; P = .003), and HLA-DPB1 mismatch reduced it in chronic myeloid leukemia (CML) (HR = 0.35; P < .001). In contrast, KIR2DL ligand mismatch in the graft-versus-host (GVH) direction (KIR-L-MM-G) increased in ALL (HR = 2.55; P = .017). An increased rejection rate was observed in KIR2DL ligand mismatch in the host-versus-graft direction (HR = 4.39; P = .012). Acute GVH disease (GVHD) was increased not only in the mismatch of HLA-A, -B, -C, and -DPB1, but also in KIR-L-MM-G. As a whole, the mismatch of HLA-A, -B, and -DQB1 locus and KIR-L-MM-G resulted in increased mortality. In conclusion, not only the mismatch of HLA-C and -DPB1, but also KIR-L-MM-G affected leukemia relapse, which should be considered based on leukemia cell type. Furthermore, KIR-L-MM induced adverse effects on acute GVHD (aGVHD) and rejection, and brought no survival benefits to patients with T-cell-replete UR-BMT.
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PMID:Effects of HLA allele and killer immunoglobulin-like receptor ligand matching on clinical outcome in leukemia patients undergoing transplantation with T-cell-replete marrow from an unrelated donor. 1731 85

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.
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PMID:Current status of hematopoietic stem cell transplantations in Vietnam. 1872 91


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