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)

Late-onset renal failure occurs in up to 20% of survivors of bone marrow transplantation. Total body irradiation is a major factor in this syndrome, so-called bone marrow transplant nephropathy (BMT NP), which is defined by disproportionate anemia, hypertension, and azotemia. Previous or concurrent chemotherapy may potentiate the effect of radiation on the kidney. Kidney function may decline acutely or more gradually, with eventual long-term stabilization. Patient survival is associated with control of the blood pressure. BMT NP is a recognized complication of bone marrow transplantation, which will require ongoing attention.
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PMID:Bone marrow transplant nephropathy: radiation nephritis revisited. 756 7

Angiotensin-converting enzyme (ACE) inhibitors can be used to prevent the development of radiation nephropathy after BMT. In previous BMT nephropathy studies, ACE inhibitor therapy was started pre-BMT and continued indefinitely. In preparation for clinical trials, studies were designed to determine whether effective prophylaxis could be achieved if ACE inhibitor therapy was started after engraftment, and to determine whether ACE inhibitors needed to be given indefinitely. The present studies in our rat syngeneic BMT model showed that captopril therapy started 25 days post-BMT was as effective as therapy started prior to BMT. When ACE inhibitor therapy was discontinued 28 weeks after BMT, the protective effect was not lost if adequate control of azotemia had been maintained for 26 weeks. If adequate control of azotemia was not maintained for 26 weeks, BMT nephropathy progressed rapidly when ACE inhibitor therapy ended, and slowly when it was continued. Failure to control azotemia was a better predictor of renal failure than failure to control hypertension or proteinuria. Based on these preclinical studies, it would appear that ACE inhibitor therapy will be effective in the prophylaxis of BMT nephropathy even if begun after engraftment, and that ACE inhibitors may not need to be given indefinitely.
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PMID:Noncontinuous use of angiotensin converting enzyme inhibitors in the treatment of experimental bone marrow transplant nephropathy. 915 51

A 64-year-old woman underwent an ileocecal resection for ileus. The specimen revealed a diffuse large B cell lymphoma. The diagnosis was stage IIA non-Hodgkin's lymphoma. She received chemotherapy with the CHOP-etoposide regimen, resulting in partial remission. High-dose etoposide was used for PBSC mobilization before auto-PBSCT. Conditioning was ranimustine, carboplatin, etoposide and cyclophosphamide. Her renal function deteriorated gradually, starting 3 months post-PBSCT. Eight months post-transplant, serum creatine concentration was 7.1 mg/dl, and BUN was 59.2 mg/dl. Her hemoglobin concentration decreased to 5.3 g/dl, with no evidence of hemolysis. Renal biopsy revealed fibrous crescent formations in glomeruli, and mononuclear cell infiltration in interstitial spaces. Renal injury in this patient differs from BMT nephropathy, which is similar to hemolytic uremic syndrome, and represents another type of late renal injury after PBSCT.
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PMID:Crescentic glomerulonephritis developing 3 months after autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma. 981 4

Chronic renal failure is an acknowledged late complication of BMT. It is related to the intensive chemotherapy, radiation and supporting medications. Polymorphism in the angiotensin converting enzyme (ACE) gene is associated with progression of nephropathy caused by diabetes and IgA nephropathy. We sought to determine whether ACE genotype and other clinical factors were associated with loss of renal function after BMT. We determined the genotype of 106 adult allogeneic BMT recipients, who received a similar preparative regimen, survived 1 year, and had assessment of renal function up to 3 years after BMT. We found that the distribution of genotypes was similar to the general population; 29%, 51%, and 20% for the DD, DI, and II genotypes, respectively. There was no statistical difference in patient survival between the three groups. Among all patients, the average creatinine clearance declined from 124 (95% CI 117, 131) to 89 (95% CI 78, 100) ml/min over the 36 months after BMT. Decline in renal function over time was less for patients with the DD compared to the II genotype (P = 0.040). Renal function in patients with the DD genotype was also better than those with the DI genotype, but this was of borderline statistical significance (P = 0.055). Renal shielding reduced decline in renal function compared to no shielding (P = 0.026). We conclude that the ACE genotype does not seem to influence survival, but the DD genotype may be protective against renal injury after BMT. Furthermore, we confirm that renal shielding during TBI reduces the renal injury after BMT.
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PMID:Loss of renal function following bone marrow transplantation: an analysis of angiotensin converting enzyme D/I polymorphism and other clinical risk factors. 1131 76

Acute leukemia is the most common form of childhood cancer and is the primary cause of cancer-related mortality in children. In the United approximately 3250 cases are diagnosed annually in children and adolescents younger than 20 years, of whom 2400 have acute lymphoblastic leukemia (ALL). Treatment results in childhood ALL continue to improve, and the expected current cure rates approach 75 to 80% of all children with ALL, including T-ALL and mature B-cell ALL, the two variants that, not too long ago, had a considerably poorer prognosis compared with the common form of BpALL. The most significant new development in the past 2 years has been the development of further evidence for fetal origin of childhood leukemias, and additional evidence to support the notion that postnatal events modulating the events of immune-mediated elimination of these leukemic clones play a major role in the eventual development of clinical disease. Other epidemiologic developments include (1) increased appreciation of the role of drug-metabolizing enzymes, both in determining the predisposition to leukemia and response to therapy; and (2) both clinical observations and gene expression studies seeming to identify a new approach to the evaluation and treatment of children with MLL (11q23) rearrangements. A most remarkable new development in the induction therapy of childhood leukemia and lymphoma in the United States is the use of urate oxidase for prevention of tumor lysis syndrome and the associated uric acid nephropathy. Drug resistance, determined either on leukemic blast cells in vitro or by studies of MRD, is being looked at critically in an effort to improve the treatment results further. Consolidation with HDMTX has gained wider popularity with the realization that effective CNS prophylaxis can be achieved with intrathecal therapy plus HDMTX for consolidation. In contrast to ALL, the progress in the therapy of acute myeloid leukemia (AML) lags behind, with cure rates of approximately 40 to 50%. There is no convincing evidence for substitution of daunorubicin with other anthracyclines, nor evidence for using high-dose cytarabine during induction in childhood AML. Rather, a 3 + 10 regimen with total daunorubicin 180 mg/m2 and cytarabine 100 to 200 mg/2 for 10 days appears to yield the best results. The most important component of the postremission chemotherapy continues to be several courses of high-dose cytarabine. The results from the MRC 10, LAME 89/91 studies and the recent BFM 93 trial with high-dose cytarabine and mitoxantrone suggest that there may be some benefit to including this combination in the postremission phase of AML. Despite these improvements in chemotherapy, allogeneic BMT from a matched family donor remains the best option for most patients (excluding Down syndrome, APL, and possibly those with inv16). Newer prognostic markers of interest include FLT3/ITD and minimal residual disease at the end of induction therapy.
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PMID:Recent advances in pediatric acute lymphoblastic and myeloid leukemia. 1249 Jul 58

We report a patient who developed chronic renal failure 11 months after an allogeneic hematopoietic stem-cell transplantation (HSCT) for Ph1(+) acute lymphocytic leukemia. Renal biopsy showed typical pathological findings compatible with a bone marrow transplant nephropathy (BMT nephropathy). The general course of BMT nephropathy is slowly progressive, eventually reaching endstage renal failure. Intervention therapy with an angiotensin-converting enzyme inhibitor (ACE-I), temocapril, was started for this patient, based on several experimental reports showing the protective effects of ACE-Is on BMT nephropathy. After the induction of ACE-I in this patient, the rate of regression of renal function was significantly reduced and his serum creatinine was maintained at almost the same level for 18 months. Although the course of observation in this patient was short, we clearly showed the effects of an ACE-I on preventing BMT nephropathy from progressing to endstage renal failure in a human rather than in an experimental model.
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PMID:Bone marrow transplant nephropathy successfully treated with angiotensin-converting enzyme inhibitor. 1654 82

Previously we have shown that bone marrow (BM) transplantation (BMT) can attenuate progression of and even ameliorate mesangial sclerosis (MS) in Wt1-heterozygous mice. However, it is unclear whether BMT performed before the onset of disease will prevent the development of MS. To investigate whether intravenous (i.v.) or intrarenal (i.r.) administration of BM have equal effects on the progression of MS in Wt1-heterozygous mice, young Wt1-heterozygous mice that had not yet developed renal disease were used as recipients for BMT. After preconditioning with 750 cGy radiation, mice were transplanted with one million wild-type BM via i.v. or i.r. administration. All recipients and untreated controls were assessed for urinary albumin loss, renal pathology, and BM donor-derived renal cells over time. Representative kidney samples were subjected to transmission electron microscopy (TEM) analysis. Interestingly, i.r. and i.v. administration of BM cells gave comparable hematopoietic engraftment levels, and both were able to prevent the onset of MS as assessed by improved lifespan, renal function, renal histology, and TEM analysis. Taken together, we show for the first time that MS can be prevented if BMT is performed before disease onset. Similar therapeutic effects were obtained whether the BM was administered i.v. or i.r.
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PMID:Prevention of mesangial sclerosis by bone marrow transplantation. 1685 25

Recent development of hematopoietic cell transplantation (HCT) has greatly improved the quality of life in critical patients with hematological malignancies. On the other hand, it is a fact that some HCT survivors suffer from chronic renal failure (CRF). We attempted to examine the clinical characteristics of CRF in patients who were successfully treated with HCT in Japan. A retrospective analysis of 158 long-term survivors receiving HCT at Komagome Hospital was undertaken. CRF was designated as less than 30 mL/min of estimated GFR (eGFR) calculated by the MDRD formula. We statistically analyzed the influences of total body irradiation (TBI), graft versus host diseases (GVHD), renal impairment during HCT, new incidence of hypertension after transplantation, age, and gender on CRF, using the multivariate logistic regression analysis. Twenty-seven patients (17.1%) had CRF. Their mean ages were 33.1 +/- 8.87 years and mean eGFR levels were 20.5 +/- 9.50 mL/min/1.73 m2. Fifteen patients were recipients of TBI (55.6 %). CRF became obvious within one year after BMT in 5 patients (18.5%) and later in 22 patients (81.5%). Seven patients(25.9%) finally reached end-stage renal disease (ESRD) at the time of over 10 years after HCT. Multivariate logistic regression analysis showed that TBI, renal impairment during HCT, and new incidence of hypertension after HCT were significantly associated with CRF. Considering that 12 patients without TBI (44.4%) developed CRF, "renal impairment during HCT", the odds ratio of which was the highest, might be the factor most closely associated with CRF. The clinical course of a representative patient who developed ESRD was described. An increase in ESRD patients receiving HCT should be anticipated and would constitute a new important issue in nephrology.
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PMID:[Chronic renal failure in patients successfully treated with hematopoietic cell transplantation]. 1842 68