Treatment of newly diagnosed children and adolescents with acute myeloid leukemia: a Childrens Cancer Group study.

Wells, Robert J.; Woods, William G.; Buckley, Jonathan D.; Odom, Lorrie F.; Benjamin, Denis R.; Bernstein, Irwin D.; Betcher, Donna L.; Feig, Stephen A.; Kim, T; Ruymann, Frederick B.

doi:10.1200/jco.1994.12.11.2367

Cited by 121 publications

(92 citation statements)

References 24 publications

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“…[1][2][3][4] However, less than one-third of children have a sibling donor, and nearly 50% of patients relapse after achieving a first CR with chemotherapy alone. [5][6][7] About 50% of children who receive re-induction chemotherapy for a first relapse achieve a remission, and their probability of a second relapse is in excess of 75%. [6][7][8][9] For children with AML beyond first CR, allogeneic BMT may offer the only chance for cure, but the clinical outcome of these patients has not been clearly defined.…”

Section: Discussionmentioning

confidence: 99%

Outcome of allogeneic bone marrow transplantation for children with advanced acute myeloid leukemia

Nemecek

Gooley

Woolfrey

et al. 2004

Bone Marrow Transplant

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Summary:Allogeneic bone marrow transplantation (BMT) may offer the only chance of cure for children with acute myeloid leukemia (AML) in second complete remission (CR2) or with relapsed disease, but the outcome of these patients has not been clearly defined. We conducted a retrospective study of 58 children, median age 7.4 years (range 0.8-17.3), who received matched related or unrelated BMT at our institution for AML in CR2 (n ¼ 12), in untreated first relapse (n ¼ 11) or with refractory disease (n ¼ 35), to identify risk factors associated with disease-free survival (DFS). Life threatening to fatal regimen-related toxicity was observed in 22% of patients. Estimates of DFS at 5 years (95% confidence interval) for patients in CR2, with untreated first relapse and refractory disease were 58% (27-80%), 36% (11-63%) and 9% (2-21%), respectively. Non-relapse mortality estimates were 0%, 27% (0-54%) and 17% (5-30%), and relapse estimates were 42% (14-70%), 36% (8-65%) and 74% (60-89%), respectively. Advanced disease phase and cytogenetic abnormalities at the time of transplantation were each associated with decreased DFS and increased relapse in multivariable regression models. Survival for children transplanted in CR2 or untreated first relapse is higher than that previously reported, but relapse remains the major cause of treatment failure regardless of disease stage.

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Section: Discussionmentioning

confidence: 99%

Outcome of allogeneic bone marrow transplantation for children with advanced acute myeloid leukemia

Nemecek

Gooley

Woolfrey

et al. 2004

Bone Marrow Transplant

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“…1 Intensification of chemotherapy has led to remissions in 70-85% of individuals with AML, and postremission relapses occur frequently. 2,3 Recent studies found that the genotype of mutant nucleophosmin (NPM1) without FLT3 internal tandem duplications and the mutant CCAAT/enhancer-binding protein-a (CEBPA) were significantly associated with complete remission in individuals with cytogenetically normal AML. 4 In addition, these studies found that individuals with wild-type NPM1 benefited from hematopoietic stem cell transplantation from an HLA-matched related donor; 4 however, regimen-related toxicities and relapse remain serious problems.…”

Section: Introductionmentioning

confidence: 99%

Blockade of mTOR signaling potentiates the ability of histone deacetylase inhibitor to induce growth arrest and differentiation of acute myelogenous leukemia cells

et al. 2008

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This study found that MS-275, a novel synthetic benzamide histone deacetylase inhibitor (HDACI), blocked Akt/mammalian target of rapamycin (mTOR) signaling in acute myelogenous leukemia (AML) HL60 and acute promyelocytic leukemia (APL) NB4 cells, as assessed by decreased levels of the phosphorylated (p)-Akt, p-p70 ribosomal S6 kinase (p70S6K) and p-S6K by western blot analysis. Interestingly, further inactivation of mTOR by rapamycin analog RAD001 (everolimus) significantly enhanced MS-275-mediated growth inhibition and apoptosis of these cells in parallel with enhanced upregulation of p27 kip1 and downregulation of c-Myc. In addition, RAD001 potentiated the ability of MS-275 to induce differentiation of HL60 and NB4 cells, as measured by the expression of CD11b cell surface antigens, as well as reduction of nitroblue tetrazolium. Importantly, RAD001 potentiated the ability of MS-275 to induce the expression of the myeloid differentiation-related transcription factor, CCAAT enhancer-binding protein-e, in these cells in association with enhanced acetylation of histone H3 on its promoter. Furthermore, RAD001 (5 mg/kg) significantly enhanced the effects of MS-275 (10 mg/kg) to inhibit proliferation of HL60 tumor xenografts in nude mice without adverse effects. Taken together, concomitant administration of an HDACI and an mTOR inhibitor may be a promising treatment strategy for the individuals with a subset of human leukemia.

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“…The outcome of the therapy has been described. 14 In this paper, univariate and multivariate methods are used to describe possible relationships between pretreatment characteristics and induction measurements, and obtaining an initial complete remission (CR), or prolonged survival from diagnosis (OS).…”

Section: Introductionmentioning

confidence: 99%

Prognostic variables in newly diagnosed children and adolescents with acute myeloid leukemia: Children's Cancer Group Study 213

et al. 2002

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The objective of this study was to identify biologic parameters that were associated with either exceptionally good or poor outcome in childhood acute myeloid leukemia (AML). Among the children with AML who entered Children's Cancer Group trial 213, 498 patients without Down syndrome or acute promyelocytic leukemia (APL) comprise the basis for this report. Univariate comparisons of the proportion of patients attaining complete remission after induction (CR) indicate that, at diagnosis, male gender, low platelet count (р20 000/ l), hepatomegaly, myelodysplastic syndrome (MDS), French-AmericanBritish (FAB) category M5, high (Ͼ15%) bone marrow (BM) blasts on day 14 of the first course of induction, and +8 are associated with lower CR rates, while abnormal 16 is associated with a higher CR rate. Multivariate analysis suggests high platelet count at diagnosis (Ͼ20 000/ l), absence of hepatomegaly, р15% day 14 BM blast percentage, and abnormal 16 are independent prognostic factors associated with better CR. Univariate analysis demonstrated a significant favorable relationship between platelet count at diagnosis (Ͼ20 000/ l), absence of hepatomegaly, low percentage of BM blasts (р15%), and abnormal 16 with overall survival. Absence of hepatomegaly, р15% day 14 BM blast percentage, and abnormal 16 were determined to be independent prognostic factors associated with better survival. Leukemia (2002) 16, 601-607.

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Treatment of newly diagnosed children and adolescents with acute myeloid leukemia: a Childrens Cancer Group study.

Abstract: The 5-year EFS rate of patients with AML is 31% and has improved. The five-drug induction regimen is no better than standard induction, BMT appears superior to chemotherapy, and maintenance therapy was not beneficial.

Cited by 121 publications

References 24 publications

Outcome of allogeneic bone marrow transplantation for children with advanced acute myeloid leukemia

Outcome of allogeneic bone marrow transplantation for children with advanced acute myeloid leukemia

Blockade of mTOR signaling potentiates the ability of histone deacetylase inhibitor to induce growth arrest and differentiation of acute myelogenous leukemia cells

Prognostic variables in newly diagnosed children and adolescents with acute myeloid leukemia: Children's Cancer Group Study 213

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