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)

Detection of minimal residual disease is one of the major goals in bone marrow transplantation. We used a fluorescence in-situ hybridization technique to detect residual Philadelphia-chromosome positive cells in chronic myelogenous leukemia (CML) patients after sex-mismatch BMT. We analyzed the level of detection using probes for the BCR/ABL fusion product by comparison with results obtained with probes for the Y and X sex chromosomes. Detection of sex-mismatch chromosomes was significantly higher than that of the BCR/ABL translocation. In contrast, a higher specificity of residual tumor cell detection by the BCR/ABL probe was demonstrated because most of the sex-mismatch cells detected by FISH had a normal karyotype. Tumor-specific markers probes are thus superior and more accurate than sex-mismatch probes for detection of MRD in CML patients after BMT.
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PMID:Detection of minimal residual disease after sex-mismatch bone marrow transplantation in chronic myelogenous leukemia by fluorescence in situ hybridization. 817 87

Current progressive chemotherapy and transplantation induce not only remission but complete cure. By this reason, the detecting system for MRD must be established in complete remission phase. In this study, we showed the detecting for MRD by molecular biology techniques in the patients with non-Hodgkin's lymphoma, CML, B-ALL and AML. 1) Malignant cells could be detected in peripheral blood or bone marrow cells by Southern blot analysis in 15 of 30 patients with non-Hodgkin's lymphoma. 2) In CML patients, BCR/ABL fusion gene was positive by RT-PCR for 6 months after BMT, 4 patients became undetectable for 7 months after BMT. 3) Rearrangement of Ig H has been disappeared in 12 months after achieved complete remission the patients with B-ALL. In conclusion, the detection for MRD remain an important goal for therapy including chemotherapy and bone marrow transplantation in hematopoetic malignancy.
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PMID:[Detection of residual malignant cells in patients with hematopoietic malignancy]. 831 24

Results for adult ALL have improved, with CR rates of 68% to 91% and a cure rate of 25% to 41%. The outcome for patients with T-ALL has especially improved, and the major drugs responsible are C and ara-C. Outcome for B-ALL has improved by using short intensive cycles including, among other drugs, C and high-dose MTX. The inferior outcome of adult ALL compared with childhood ALL seems related to the high proportion of Ph1/BCR-ABL positive ALL patients, which constitute about 30% in adults versus less than 5% in children. The major prognostic factors for survival in adult ALL are age, time to achieve CR, cytogenetic abnormalities, immunologic subtype, and WBC; these may serve as a guide for BMT in first CR. New approaches in the treatment of adult ALL include the use of HGFs, the use of biologic response modifiers, and the detection of MRD to tailor treatment decisions.
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PMID:Therapy of the newly diagnosed adult with acute lymphoblastic leukemia. 844 56

In the twelve years since the first PBSCT were reported, impressive advancements in BCT techniques have made it easy to perform, effective, less costly, rapid haematologically recoverable, reduced morbidity and mortality, shorten overall duration of cancer treatment and hospital stay. Development of high-dose chemotherapy and new novel effective antitumor drugs otherwise limited by haematological toxicities may now become possible. Treatment of haematological malignancies with purged autologous PBPCT, e.g. Ph Chromosome negative progenitor cells in CML or with immunologically manipulated allogeneic PC having preserved GVL but not GVHD action, with hopeful prospects, is now becoming possible. Tailoring of BC for ex-vivo selection and expansion of specially active T Iymphocytes, NK cells and other immune effector cells will enable adoptive immunotherapeutic approach and treatment of Minimal residual disease [MRD] after high-dose chemotherapy both in grafts and in patients. The discovery of a nonhaematopoietic, engraftment facilitator cell form donor BM may usher in further precision in GVHD prevention by purification and in adoptive immunotherapeutic approach. Therefore, it is likely that BCT will supersede BMT, though the follow-up is too short to draw conclusions.
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PMID:Peripheral blood cells transplantation--a review article. 1075 57

Overall, the MRC Adult Leukaemia Trials have been successful, in that since the 1970s they have demonstrated a stepwise improvement in outcome. Examination of the survival curves shows the DFS rate at 5 years in UKALL Trial 1 of 5% rising to 38% in UKALL Trial XII (year 2000). Unfortunately, compared with children with ALL, these results in adults must be regarded as poor, because in the UKALL children's trials the EFS rate at 5 years for a child entered in the year 2000 is expected to be above 80%. With a low proportion of all adults entered into randomized trials, one cannot be certain that improvements result from treatment rather than patient selection. Only recently have randomized trials in adults become large enough to detect plausible treatment effects. The authors believe that the main contribution of these trials so far, confirmed by other groups, is in examining prognostic features in al patients and finding that age and the presence of the Ph chromosome, independent of WBC count, gender, and cell type, is the main feature for predicting outcome. The UKALL XII trial will provide valuable information on the relative merits of transplantation and molecular studies of MRD. An in-depth study of a large number of Ph chromosome-positive ALL leukemias will also provide information on which to base future studies. Preliminary data suggest that all Ph-positive patients should undergo some sort of allograft early after CR is achieved, because these patients are not rescued by BMT after relapse. At the time of the publication of this article, preliminary studies suggest that STIs may not be as effective in Ph-positive ALL as in chronic granulocytic leukemia. The challenge for the future is to understand the biologic role of age and its impact on outcome so as to overcome "ageism" in adult ALL.
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PMID:The Medical Research Council trials in adult acute lymphocytic leukemia. 1114 26

We report a case of autologous hematopoietic recovery with durable leukemic remission after BMT from a phenotypically HLA-identical donor in a 30-year-old male with CML. Graft loss was diagnosed from day 60 post-BMT by VNTR PCR. To assess for the presence of a minor donor-derived T cell population that could exert an anti-leukemic effect, we serially applied a sensitive process of chimerism analysis by fluorescent PCR on sorted T cells. No residual donor T cells could be detected. We also showed retrospectively that a very sensitive method of MRD analysis by real-time quantitative PCR could have permitted prediction of relapse in this case.
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PMID:Autologous reconstitution combined with durable leukemic remission after allogeneic BMT for CML: absence of persistence of a donor-derived T cell effector population. 1170 98

The accuracy of cytogenetic diagnosis in the management of hematological malignancies has improved significantly over the past 10 years. Fluorescence in situ hybridization (FISH), a technique of molecular cytogenetics, has played a pivotal role in the detection of unique sub-microscopic chromosomal rearrangements that helped in the identification of chromosomal loci, which contain genes involved in leukemogenesis. We studied the feasibility and sensitivity of the FISH technique for molecular analysis of translocations markers, t(9;22) and t(15;17) for accurate molecular diagnosis and for monitoring the disease in 21 patients with chronic myeloid leukemia (CML) who received interferon-alpha and/or chemotherapy (7 patients), bone marrow transplantation (14 patients), and 14 patients with acute promyelocytic leukemia (APL) who received all-trans-retinoic acid (ATRA) and/or chemotherapy. We also applied conventional karyotyping (CK) for identification of t(9;22) and t(15;17) at diagnosis. All CML cases had a Ph; t(9;22) and except for two cases all APL had t(15;17). The FISH studies on CML marrows in complete cytogenetic remission (CCR) (100% Ph- by CK) achieved by IFN-alpha, showed 0-2.5% of cells with BCR-ABL fusion in first cytogenetic remission (Controls, range 0.5-1.5%). Repeat follow-up FISH studies could be done in two cases in remission, which demonstrated 0-10% of cells with BCR-ABL fusion. Evaluation of Ph positive status of CML marrow at diagnosis by CK (100% Ph+ cells) and FISH (80-92% BCR-ABL fusion) pointed the existence of dormant clone of normal residual hematopoietic cells along with actively proliferating clones of Ph positive cells. Fluorescence in situ hybridization analysis of post-BMT CML marrows in CCR (0% Ph+ mitoses) could detect MRD with range of 1-6%. Among 14 patients, 9 who showed percentage of BCR-ABL positive cells (0.0-1.5%) almost similar to normal controls, 6 patients had comparatively good prognosis (disease-free survival 7-14 months). Of five patients with residual leukemic cells in the range of 2-6%, 4 relapsed within a period of 3-24 months. Fourteen APL patients in CCR [100% t(15;17) negative cells by CK] were evaluated by FISH to check the presence of residual leukemic cells. In these patients FISH could efficiently detect 1-14.5% of residual cells with PML-RARA (patients mean MRD 5%, controls mean MRD 3.5%, P=.02). Since the time of FISH analysis, 5 to 7 patients with higher fraction of leukemic cells (5-11%) relapsed within a short period (1-7 months). On the contrary, 5 of 7 patients with either absence or low percentage of PML-RARA positive cells remained in complete remission for 11-24 months. Our data show that FISH has a potential to detect and measure the fraction of aberrant malignant cells in remission marrows, induced by BMT in CML and chemotherapy in APL. These findings encourage the investigations on a large scale to merit its potential for identification of patients at high risk. In the present studies, FISH on interphase cells also demonstrated its efficiency in the molecular diagnosis by its ability to detect BCR-ABL and PML-RARA fusion in CML with masked/variant Ph and t(15;17) negative APL, respectively. The efficiency of technique in molecular diagnosis was also proved in one of the CML patients who progressed to myeloid blastic phase where interphase FISH could identify an extra BCR-ABL fusion on both chromosomes 9 indicating insertion of BCR into ABL and its duplication.
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PMID:Fluorescence in situ hybridization: a highly efficient technique of molecular diagnosis and predication for disease course in patients with myeloid leukemias. 1175 52

High MRD levels before transplantation in children receiving T cell-depleted unrelated grafts for relapsed ALL were associated with a 100% relapse risk. We report on two children with relapsed ALL who underwent non T cell-depleted BMT from unrelated donors. Despite a high residual tumor load pre- transplant and the occurrence of only aGVHD grade I, they are still in second complete remission 2.7 and 5.2 years after transplantation, respectively. Thus, we propose that the transplant regimens influence the prognostic significance of high MRD levels pre-BMT.
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PMID:Influence of transplantation regimen on prognostic significance of high-level minimal residual disease before allogeneic stem cell transplantation in children with ALL. 1178 21

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 39-year-old female patient who underwent HLA-identical sibling allogeneic BMT for CML in accelerated phase. Severe pancytopenia refractory to G-CSF associated with progressive splenomegaly and RBC/platelet transfusion dependency were present from day +60 after BMT. MRD assessed by FISH and RT-PCR multiplex for BCR-ABL rearrangement was negative, and complete chimerism was documented by VNTR on days +100, +180, +360 and 2 years after BMT. Splenectomy was performed on day +225 and pancytopenia resolved but chronic extensive graft-versus-host disease developed, with hepatic cholestasis, diffuse scleroderma and sicca-like syndrome. She was sequentially and progressively treated with different immunosuppressive therapy combinations with no clear benefit. On day +940, she presented with infection over the previously present ulcers on both limbs, which culminated in septic shock and death on day +1041. We conclude that, although splenectomy may reverse poor graft function after allogeneic BMT, hyposplenism may trigger or worsen chronic extensive GVHD leading to increased morbidity and mortality.
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PMID:Refractory chronic GVHD emerging after splenectomy in a marrow transplant recipient with accelerated phase CML. 1285 7


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