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)

Patients who received bone marrow transplantation (= BMT) for the treatment of severe combined immunodeficiency (= SCID), and who were reported in the medical literature from 1968 to 1977, were collected and analysed. Eighteen of these 80 children are still alive, 10 months to 9 years after transplantation. It is thus the first successful form of therapy for this otherwise invariably fatal disease. Fifteen of the 18 survivors received bone marrow cells from HLA and MLC compatible donors; the remaining 3 survivors received grafts from MLC-compatible but HLA-incompatible donors. Bone marrow transplantation is the treatment of choice for SCID when recipient and donor are HLA- and MLC-identical. All patients who received MLC-incompatible grafts died, and bone marrow transplantation for SCID from MLC-incompatible donors should be abandoned. Milt-to-severe graft-versus-host disease (= GVHD) occurred in spite of HLA- and/or MLC-compatibility, with some correlation to the number of cells transplanted. This should preferably be kept below 50 million cells per kilo body weight. Infection was the chief cause of death in all groups. Strict reverse isolation, bowel decontamination and routine pre- and post-transplant Pneumocystis carinii prophylactic treatment are recommended. The clinical picture and laboratory findings of these 80 children before BMT did not differ from non-transplanted SCID patients. Three of the 18 survivors are adenosinedeaminase deficient.
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PMID:Bone marrow transplantation for severe combined immunodeficiency disease. Reported from 1968 to 1977. 3 63

We previously demonstrated that, following a 2-day stimulation of T cells by MHC incompatible cells, a ricin A-chain conjugated to a monoclonal anti-IL2 receptor p55 subunit can kill 1.5 log of the activated alloreactive T cells while non specific killing of alloreactive T cells of a third partner does not exceed 0.5 log. This methodology is of potential use for selective alloreactive T cell depletion in MHC incompatible bone marrow transplantation in order to prevent both graft versus host disease and graft rejection. This study shows that this T cell depletion method does not alter T cell reactivity to microorganism antigens encountered in infection following BMT. It was found that T cell proliferation to cytomegalovirus and to candida antigens is not affected as shown in proliferative assays and by limiting dilution analysis for the latter antigen.
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PMID:[Residual lymphocytes after specific depletion. Functional study]. 129 44

Bone marrow transplantation has become the accepted treatment for several hematologic disorders. We have done 3 autologous and 6 allogeneic bone marrow transplantations at Ramathibodi Hospital since July 1989 in patients with acute lymphoblastic leukemia, acute non-lymphocytic leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma and severe aplastic anemia. Only one patient with aplastic anemia had late graft rejection, but the rest of them engrafted and did well during the median follow up period of 317 days (range: 39 to 962 days) post transplantation. None of the allogeneic BMT had graft-versus-host disease. We use cyclosporin and short course methotrexate for post transplantation immunosuppression.
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PMID:Bone marrow transplantation in Ramathibodi Hospital: progress report. 130 13

CMV infection is the major infectious complication following bone marrow transplantation. It is most often related to reactivation of latent infection in patients who were CMV seropositive before BMT. The incidence and severity have recently been modified by the use of preventive and curative treatments. Prevention of CMV infection with the transfusion of seronegative blood products is useful only when donor and recipient are seronegative. High-dose acyclovir has been shown effective in one randomized study. A multicenter study is currently being performed in Europe to confirm this result. Intravenous gammaglobulins seemed to lower the number of patients who incur interstitial pneumonitis but not the incidence of viremia. They also decreased the incidence of gram-negative sepsis and severe GVH and improved survival. The treatment is based on the use of gancyclovir. Several studies show that gancyclovir is more effective in asymptomatic patients with viral isolation from blood or bronchoalveolar lavage. The addition to gancyclovir of high-dose gammaglobulin improves survival in symptomatic patients with interstitial pneumonitis. This progress in the prevention and treatment of CMV infection has improved the overall results of allogeneic bone marrow transplantation.
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PMID:Prevention and treatment of CMV infection after allogeneic bone marrow transplant. 132 89

Ultraviolet-B irradiation (UV-B) (700 J/m2) of BM cells prior to transplantation into lethally gamma-irradiated (1050 rads) allogeneic rats prevents the development of GVHD and results in stable chimerism. This study was developed to determine if UV-B modulation of BMT is useful for preconditioning recipients for the induction of tolerance to donor islets and heart allografts. Lethally irradiated Lewis rats that received UV-B irradiated (700 J/m2) WF BMT (10(8) BM cells) demonstrated stable chimerism without any evidence of GVHD. The stable Lewis chimeras were made diabetic with streptozotocin (STZ) at 28-35 days after BMT and subdivided into 3 experimental groups that received 1000-1200 islets from WF, Lewis, or BN (third-party), respectively. The results showed that group I diabetic Lewis chimeras accepted permanently (greater than 300 days) BM donor WF islets and became normoglycemic. When 3 of 6 Lewis chimeras transplanted with WF islets were rechallenged with WF hearts 60 days after islet grafts, they accepted both islets and cardiac allografts permanently (greater than 240 days). Similarly, the remaining 3 animals accepted Lewis cardiac allografts permanently, thus indicating tolerance to both donor and recipient alloantigens. Group II diabetic chimeras accepted permanently (greater than 300 days) recipient (Lewis) islets. In contrast, group III chimeras rejected acutely (7-8 days) third-party (BN) islets. However, when these animals that rejected BN islets and again became diabetic were retransplanted with BM donor-type (WF) islets, they became permanently normoglycemic (greater than 200 days). This finding emphasizes the specificity of the induction of tolerance in this model and the apparent lack of organ-specific sensitization. To define the underlying mechanism of tolerance, in vivo adoptive transfer of 10(8) spleen cells to naive Lewis or WF recipients, obtained from tolerant Lewis chimeras carrying donor islets and heart allografts, showed no prolongation of cardiac allografts in the unmodified syngeneic hosts, thus questioning the role of suppressor mechanisms in the tolerant rats. Furthermore, cells from the tolerant chimeras that showed no mixed lymphocyte reaction (MLR) response to Lewis or; WF alloantigens failed to suppress anti-Lewis and anti-WF MLR-response in coculture MLR. These results suggest that tolerance to donor alloantigens in the UV-B BMT model is most likely due to selective elimination of anti-BM donor helper or effector cell precursors (clonal deletion) rather than induction of suppressor cell activity. This study demonstrates that this relatively simple and effective approach to modulation of T cells in BM treatment may be potentially useful in the induction of tolerance to donor organs.
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PMID:Induction of stable chimerism and transplantation tolerance to rat islet and heart allografts by ultraviolet-B modulation of bone marrow cells. 138 14

Severe microangiopathy resembling thrombotic thrombocytopenic purpura (TTP) has been reported as a complication of acute graft-versus-host disease (aGvHD) in patients receiving cyclosporin (CsA) prophylaxis following allogeneic BMT. In order to analyze the pathophysiological events involved in microangiopathy, a prospective study comparing release of von Willebrand Factor (vWF), t-PA and PAI, as well as TNF alpha and further coagulation parameters was performed in 32 patients. Endothelial damage as the central lesion was confirmed by the close association of vWF and t-PA:Antigen with severity of microangiopathy. t-PA activity, however, was neutralized by a simultaneous rise in PAI. Activation of coagulation in the course of microangiopathy was further confirmed by increased levels of DDimer (DDi), fibrinopeptide A (FPA), beta-thromboglobulin (beta TG) and platelet factor 4 (PF4). As clinical grades of microangiopathy, as well as the release of t-PA:Ag and PAI were correlated with systemic release of TNF alpha our data further support our hypothesis of cytokine induced endothelial damage in clinical complications following allogeneic BMT.
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PMID:Increased levels of tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor (PAI) correlate with tumor necrosis factor alpha (TNF alpha)-release in patients suffering from microangiopathy following allogeneic bone marrow transplantation (BMT). 141 3

Two patients with hematologic relapse of chronic myelogenous leukemia (CML) following allogeneic BMT were treated by abrupt discontinuation of cyclosporine. Both patients rapidly attained complete hematologic and cytogenetic remission and remain free of disease with long follow-up. In the first patient, disappearance of CML was associated with the development of graft-versus-host disease (GVHD). In the second patient GVHD did not develop until after clearing of disease had been documented by cytogenetic analysis. Laboratory studies in the second patient disclosed the presence of lytic activity against both K562 and autologous CML cells that enhanced with IL2. Correlation with serial immunophenotyping data from this patient suggests that the effector for this graft-versus-leukemia (GVL) reaction could have been a T lymphocyte. Abrupt discontinuation of post-transplant immunosuppression with cyclosporine may represent a therapeutic approach to CML which has recurred following BMT. Moreover, investigation of this clinical phenomenon in subsequent cases may permit direct study of the cellular mechanisms involved in the GVL effect.
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PMID:Hematologic relapse of chronic myelogenous leukemia following allogeneic bone marrow transplantation: apparent graft-versus-leukemia effect following abrupt discontinuation of immunosuppression. 142 99

In order to determine the incidence and causes of death during the first 100 days after BMT (early deaths) in a pediatric population we have examined data reported in the AIEOP BMT Registry. Up to July 1990, data on 486 children who underwent allogeneic (180) or autologous (306) BMT were evaluable. The children had acute lymphoblastic leukemia (148 cases), acute non-lymphoblastic leukemia (127 cases), neuroblastoma (82 cases), chronic myelogenous leukemia (15 cases), aplastic anemia (nine cases), solid tumors, lymphoma, immunodeficiency or storage diseases. The overall survival is 55% for allogeneic HLA matched and 38% for autologous transplants at 5 years, 24% for HLA mismatched graft at 2 years. Out of the 486 children, 70 (14%) died during the first 100 days after BMT: 33/306 (11%) after autologous BMT, 24/150 (16%) after allogeneic matched BMT and 13/30 (43%) after mismatched BMT. Causes of early death were as follows: disease progression: 12 children (10/306 after autologous and 2/180 after allogeneic BMT); infection: 12 children (five after autologous and seven after allogeneic BMT); interstitial pneumonitis: 21 children (seven after autologous and 14 after allogeneic BMT); cardiac failure: five children (four after autologous BMT); veno-occlusive disease: eight children (three after autologous, five after allogeneic BMT); acute renal failure: three children (one after autologous and two after allogeneic BMT); multiple organ failure: two cases (one after autologous BMT); cerebral hemorrhage: three children (one after autologous BMT); hypertension: one child; acute GVHD: three children (12% of early deaths after allogeneic BMT).
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PMID:Early deaths in children after BMT. Bone Marrow Transplantation Group of the Italian Association for Pediatric Hematology and Oncology (AIEOP) and Gruppo Italiano Trapianto di Midollo Osseo (GITMO). 146 3

Although the combination of cyclosporin A (CYA) and methotrexate has been reported to reduce the incidence of acute GVHD in patients undergoing allogeneic BMT for leukaemia, it has been associated with a higher risk of leukaemic relapse. Since 1987 we have used the combination of CYA and methotrexate for GVHD prophylaxis in 24 patients undergoing allogeneic BMT for leukaemia or myelodysplasia. Over the first 50 days post-transplantation, CYA dosage was adjusted to keep within a therapeutic range of 95-205 ng/ml. This resulted in a 60% reduction in CYA dosage by day 50 post-transplant compared to the original Seattle protocol. Despite the low dosage of CYA administered, the incidence of acute GVHD was only 25% with no patient having greater than grade I GVHD. There have been no leukaemic relapses in low risk patients. The results indicate that decreasing CYA dosage does not increase the incidence of GVHD but may reduce the risk of leukaemic relapse following allogeneic BMT.
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PMID:Effective prevention of acute GVHD following allogeneic BMT with low leukaemic relapse using methotrexate and therapeutically monitored levels of cyclosporin A. 146 5

Twenty-three consecutive patients undergoing related-donor BMT for myelodysplastic syndrome (MDS) were conditioned with a combination of busulfan (BU) and cyclophosphamide (CY). GVHD prophylaxis was with cyclosporine (CSP)/methotrexate (MTX) in 15 patients, CSP/methylprednisolone (MP) in six patients, and CSP/MP/MTX in two patients. The most frequent regimen-related toxicities were oral mucosal (87% of patients, 61% > or = grade II) and hepatic (82% of patients, 43% > or = grade II). The overall incidence of grade II-IV acute GVHD was 48% with eight patients dying of acute or chronic GVHD. There have been five relapses, with the cumulative risk of relapse being 35% (95% confidence interval [CI], 16%-66%). Eight patients remain alive and well (median follow-up 27 months, range 15-70 months), with an estimated 3-year event-free survival (EFS) of 35% (95% CI, 17%-54%). Univariate analysis of EFS by pretransplant variables indicated that only age < or = 35 years correlated with a favorable outcome (p = 0.04). BUCY is an effective, well-tolerated alternative conditioning regimen for MDS patients undergoing allogeneic BMT.
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PMID:Treatment of myelodysplastic syndrome with busulfan-cyclophosphamide conditioning followed by allogeneic BMT. 146 8


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