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  • 1
    Keywords: SURVIVAL ; Germany ; THERAPY ; PATIENT ; IMPACT ; TRANSPLANTATION ; BINDING ; treatment ; chromosome ; NO ; TRIAL ; EXPERIENCE ; DIFFERENCE ; AGE ; meta-analysis ; chemotherapy ; leukemia ; PROGNOSTIC-FACTORS ; allogeneic ; PROGNOSTIC FACTORS ; ALLOGENEIC TRANSPLANTATION ; PROGNOSTIC FACTOR ; relapse ; COMPLETE REMISSION ; Y-CHROMOSOME ; acute myeloid leukemia ; INTENSIVE CHEMOTHERAPY ; POSTREMISSION THERAPY ; AUTOLOGOUS TRANSPLANTATION ; ONCOLOGY ; ADULT ; ADULTS ; overall survival ; REMISSION DURATION ; METAANALYSIS ; ACUTE MYELOBLASTIC-LEUKEMIA ; ADULT PATIENTS ; CHROMOSOME-ABNORMALITIES ; DE-NOVO AML ; HIGH-DOSE CYTARABINE ; REPETITIVE CYCLES ; STANDARD CYTOGENETICS
    Abstract: Purpose To evaluate prognostic factors for relapse-free survival (RFS) and overall survival (OS) and to assess the impact of different postremission therapies in adult patients with core binding factor (CBF) acute myeloid leukemias (AML). Patients and Methods Individual patient data-based meta-analysis was performed on 392 adults (median age, 42 years; range, 16 to 60 years) with CBF AML (t(8;21), n = 191; inv(1 6), n = 201) treated between 1993 and 2002 in prospective German AML treatment trials. Results RFS was 60% and 58% and OS was 65% and 74% in the t(8;21) and inv(16) groups after 3 years, respectively. For postremission therapy, intention-to-treat analysis revealed no difference between intensive chemotherapy and autologous transplantation in the t(8;21) group and between chemotherapy, autologous, and allogeneic transplantation in the inv(16) group. In the t(8;21) group, significant prognostic variables for longer RFS and OS were lower WBC and higher platelet counts; loss of the Y chromosome in male patients was prognostic for shorter OS. In the inv(16) group, trisomy 22 was a significant prognostic variable for longer RFS. For patients who experienced relapse, second complete remission rate was significantly lower in patients with t(8;21), resulting in a significantly inferior survival duration after relapse compared with patients with inv(16). Conclusion We provide novel prognostic factors for CBF AML and show that patients with t(8;21) who experience relapse have an inferior survival duration. (C) 2004 by American Society of Clinical Oncology
    Type of Publication: Journal article published
    PubMed ID: 15289486
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  • 2
    Keywords: CANCER ; SURVIVAL ; TOXICITY ; DEATH ; RISK ; COMPLEX ; MUTATIONS ; ABNORMALITIES ; ACUTE PROMYELOCYTIC LEUKEMIA ; TOPOISOMERASE-II ; RECOMMENDATIONS ; CELL TRANSPLANTATION ; MYELODYSPLASTIC SYNDROMES ; MITOXANTRONE ; SECONDARY LEUKEMIAS
    Abstract: To study the characteristics and clinical impact of therapy-related acute myeloid leukemia (t-AML). 200 patients (7.0%) had t-AML and 2653 de novo AML (93%). Patients with t-AML were older (P 〈 .0001) and they had lower white blood counts (P = .003) compared with de novo AML patients; t-AML patients had abnormal cytogenetics more frequently, with over-representation of 11q23 translocations as well as adverse cytogenetics, including complex and monosomal karyotypes, and with underrepresentation of intermediate-risk karyotypes (P 〈 .0001); t-AML patients had NPM1 mutations (P 〈 .0001) and FLT3 internal tandem duplications (P = .0005) less frequently. Younger age at diagnosis of primary malignancy and treatment with intercalating agents as well as topoisomerase II inhibitors were associated with shorter latency periods to the occurrence of t-AML. In multivariable analyses, t-AML was an adverse prognostic factor for death in complete remission but not relapse in younger intensively treated patients (P 〈 .0001 and P = .39, respectively), relapse but not death in complete remission in older, less intensively treated patients (P = .02 and P = .22, respectively) and overall survival in younger intensively treated patients (P = .01). In more intensively treated younger adults, treatment-related toxicity had a major negative impact on outcome, possibly reflecting cumulative toxicity of cancer treatment.
    Type of Publication: Journal article published
    PubMed ID: 21127174
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  • 3
    Keywords: CANCER ; EXPRESSION ; SURVIVAL ; CELL ; Germany ; GENE ; MARKER ; prognosis ; polymorphism ; single nucleotide polymorphism ; TRIAL ; AGE ; MUTATION ; SNP ; leukemia ; MARKERS ; MUTATIONS ; HIGH-RISK ; GLIOMAS ; GENE-MUTATIONS ; STUDY-GROUP ULM ; ONCOLOGY ; overall survival ; MYELOID-LEUKEMIA ; PROGNOSTIC-FACTOR ; ALLELES ; methods ; PREDICTS ; STEM ; GROUP-B ; outcome ; IDH1 ; CODON 132 ; single nucleotide ; NUCLEOPHOSMIN ; clinical oncology ; AML STUDY-GROUP ; YOUNGER ADULTS 16
    Abstract: Purpose We assessed the prognostic impact of IDH1 R132 mutations and a known single nucleotide polymorphism (SNP) located in the same exon of the IDH1 gene in patients with cytogenetically normal acute myeloid leukemia (CN-AML) in the context of other prognostic markers. Patients and Methods IDH1 exon four was directly sequenced in 275 CN-AML patients from two subsequent AML multicenter treatment trials and 120 healthy volunteers. Moreover, mutations in NPM1, FLT3, CEBPA, and WT1 were analyzed, and mRNA expression of IDH1 was quantified. Results IDH1 R132 mutations were found in 10.9% of CN-AML patients. IDH1 SNP rs11554137 was found in 12% of CN-AML patients and 11.7% of healthy volunteers. IDH1 R132 mutations had no impact on prognosis. In contrast, IDH1 SNP rs11554137 was an adverse prognostic factor for overall survival in univariate and multivariate analysis. Other significant factors were age, NPM1/FLT3 mutational status, WT1 SNP rs16754, and platelet count. The impact of IDH1 SNP rs11554137 was most pronounced in the NPM1/FLT3 high-risk patients (either NPM1 wild-type or FLT3-internal tandem duplication positive). Patients with IDH1 SNP rs11554137 had a higher expression of IDH1 mRNA than patients with two wild-type alleles. Conclusion IDH1 SNP rs11554137 but not IDH1 R132 mutations are associated with an inferior outcome in CN-AML
    Type of Publication: Journal article published
    PubMed ID: 20368538
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