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)

We report 11 years experience with a modified version of a chemotherapy programme in use at the MRC Leukaemia Unit from 1982 to 1984, supplemented by allogeneic bone marrow transplantation in first relapse or second or later remission from 1985. 79 consecutive patients aged 15-60 years with newly diagnosed acute lymphoblastic leukaemia (ALL) were given induction chemotherapy. This included a standard DAT course (daunorubicin, cytarabine and thioguanine) applied as in acute myelogenous leukaemia approximately midway in the induction programme. A 3-year rotating maintenance programme consisted of combinations of cytotoxic drugs used in the induction therapy. CNS prophylaxis did not include CNS irradiation. Allogeneic BMT was not performed in first remission. The overall complete remission (CR) rate was 82% (65/79). 26 patients relapsed (seven first in the CNS). Seven patients underwent allogeneic BMT of whom six are alive and well with a mean observation time of 32 months (range 4-99 months) after transplantation. Three patients died in first CR. Estimated 5- and 8-year overall survival was 51% (95% confidence interval (CI) 39-63) and 47% (CI 33-61). For patients who reached CR, the corresponding figures were 63% (CI 50-76) and 57% (CI 41-73). Estimated disease-free survival in the remitters was 54% (CI 40-68) at 5 years and 44% (CI 28-60) at 8 years. Patient age below 25 years and white cell count below 15 x 10(9)/l at presentation were both found to improve the chance of overall survival.
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PMID:Estimated 8-year survival of more than 40% in a population-based study of 79 adult patients with acute lymphoblastic leukaemia. 780 61

359 eligible children with acute myeloid leukaemia (AML) entered the MRC AML 10 trial between May 1988 and March 1995. Patients received four courses of intensive induction and consolidation chemotherapy, with or without subsequent autologous (A-BMT) or allogeneic (allo-BMT) bone marrow transplant. There were randomized comparisons of thioguanine versus etoposide in induction and of A-BMT versus not. Allo-BMT was recommended for patients with a HLA-matched sibling and was evaluated by donor versus no donor comparison. The complete remission rate was 92%. In first remission there were 20 deaths during consolidation chemotherapy and 11 after BMT (8/61 allo-BMTs. 1/60 A-BMTs and 2/4 matched unrelated donor transplants). The relapse rate was low, decreasing from 26% in the first year to 2% in the fourth. Long-term outcome was excellent with survival at 7 years from entry of 56% and event-free survival of 48%. There were no significant differences between thioguanine and etoposide, whereas both A-BMT and allo-BMT reduced relapse risk but did not produce a significant survival benefit. It appears that over half the children entered into AML 10 are cured, a result which compares favourably with other reported series. We conclude that four courses of intensive chemotherapy are an effective approach to the treatment of paediatric AML, which avoids the acute toxicity and long-term side-effects of BMT and also avoids the need for prolonged maintenance therapy or cranial irradiation.
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PMID:Marked improvements in outcome with chemotherapy alone in paediatric acute myeloid leukemia: results of the United Kingdom Medical Research Council's 10th AML trial. MRC Childhood Leukaemia Working Party. 957 93

Between May 1988 and March 1995, 359 children with acute myeloid leukaemia (AML) were treated in the MRC AML 10 trial. Three risk groups were identified based on cytogenetics and response to treatment. One hundred and twenty-five children relapsed--103 in the bone marrow only, 12 in the bone marrow combined with other sites, and six had isolated extramedullary relapses (site was not known in four cases). Eighty-seven children received further combination chemotherapy, one all-trans retinoic acid for acute promyelocytic leukaemia, and one a matched unrelated donor allograft in relapse, and 61 achieved a second remission. One patient with no details on reinduction therapy also achieved second remission. Treatment in second remission varied--44 children received a BMT (22 autografts, 12 matched unrelated donor allografts, 10 family donor allografts), and 17 were treated with chemotherapy alone. The overall survival rate for all children (treated and untreated) was 24% at 3 years, with a disease-free survival of 44% for those achieving a second remission. Length of first remission was the most important factor affecting response rates--children with a first remission of less than 1 year fared poorly (second remission rate 36%, 3 year survival 11%), whereas those with longer first remissions had a higher response rate (second remission rate 75%, 3 year survival 49%, P < 0.0001).
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PMID:Outcome for children with relapsed acute myeloid leukaemia following initial therapy in the Medical Research Council (MRC) AML 10 trial. MRC Childhood Leukaemia Working Party. 1004 56

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

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