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)

Of 52 children aged 9 months to 16 years old with acute myelogenous leukaemia (AML) in first complete remission undergoing bone marrow transplantation at our institution, 31 received allogeneic transplants (allo-BMT) and 21 received autologous transplants (ABMT). Initial induction and consolidation chemotherapy were not uniform. BMT was performed at a median of 7 months (range: 2.5 to 22.5 months) from the diagnosis. Conditioning included chemotherapy (n=43: 4 x 4 mg/kg of busulfan and 3 x 60 to 70 mg/m(2) of melphalan) or total body irradiation (12 Gy) plus chemotherapy (n=9). Graft-versus-host disease (GVHD) prophylaxis in allo-BMT cases consisted of methotrexate +/- cyclosporin A. Unpurged marrow was used in ABMT cases. All patients showed sustained engraftment. Amongst allograft cases, acute or chronic GVHD developed in 7 patients each (23%). 8 patients (15%) died (5 with allo-BMT, 3 with ABMT), including transplant-related mortality in 3 of the allo-BMT patients. 7 patients had relapses (3 with allo-BMT, 4 with ABMT). As of June 1999, 43 patients are alive and well 13 to 160 months after BMT (median, 71), with 5-year disease-free survival rates after BMT of 84% for allo-BMT, 81% for ABMT and 83% altogether. Although the presented data are based on a retrospective evaluation, we consider BMT for childhood AML during first complete remission an effective treatment for eradicating leukaemia.
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PMID:Bone marrow transplantation for children with acute myelogenous leukaemia in the first complete remission. 1070 39

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

Childhood and adolescent acute myeloid leukemia (AML) is traditionally one of the hardest childhood cancers to successfully treat and had an overall survival well under 10% in the 1960s. Initial progress was made by three major events: (1) active chemotherapeutic agents were identified which led to remissions for the first time in this disease; (2) cooperative groups were instituted leading to important clinical trials; and (3) several single institutions began experimenting with the role of allogeneic matched sibling donor (MSD) BMT as effective intensification. Over the last 25 years, the cure rate has improved from <20% to 50% or higher. Most of the clinical research during this time of great advancement focused on two major themes: (1) the role of aggressive induction therapy in not only improving CR rates but in post-remission outcomes; and (2) the role of aggressive post-remission therapy in further improving survival, with an emphasis on high-dose Ara C-based chemotherapy, BMT, and supportive care. But we have "miles to go before we sleep." Some of the challenges that will lead to ongoing reduction of population-based mortality for AML through young adulthood include: (1) improving access of adolescents to pediatric AML therapy; (2) stratification by prognostic factors; (3) individualized therapy based on individual genetics and leukemia cell biology; (4) and the use of novel therapies including targeted immuno-conjugates and "small molecules" which disrupt abnormal signal transduction pathways. This brief review looks at both the advances over the last three decades as well as discusses the challenges moving forward for ultimately curing all children with this disease.
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PMID:Curing childhood acute myeloid leukemia (AML) at the half-way point: promises to keep and miles to go before we sleep. 1626 62

We retrospectively investigated the outcomes of HLA-matched unrelated BMT (MU-BMT, n = 13) and HLA-identical sibling donor BMT (MS-BMT, n = 17) for childhood AML in CR1 between June 2002 and August 2005. Engraftment of neutrophil and platelet did not differ between the two transplant groups. The cumulative incidence of grade II-IV acute GVHD and any chronic GVHD at three yr was not different between MS-BMT and MU-BMT. Of the 30 patients, four patients experienced relapses (three with MS-BMT, one with MU-BMT) and four patients died of transplant-related complications (two with MS-BMT, two with MU-BMT). A total of 23 patients survived with a median follow-up of 43.2 months. The Kaplan-Meier estimates for EFS rates at three yr were 71% and 77% for MS-BMT and MU-BMT, respectively, and the OS rates were 76% and 77% for MS-BMT and MU-BMT, respectively. The outcome of HLA-matched unrelated BMT is comparable to that of HLA-identical sibling BMT for childhood AML in CR1. HLA-matched unrelated BMT may be recommended for patients who have AML in CR1 without an HLA-matched sibling donor.
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PMID:Comparable outcomes of HLA-matched unrelated and HLA-identical sibling donor bone marrow transplantation for childhood acute myeloid leukemia in first remission. 1862 12