RESUMO
Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a variable clinical course. The aim of this study was to evaluate whether a combination of genetic parameters can improve prediction of outcome irrespective of clinical stage. The prognostic impact of chromosome banding analysis (CBA) in addition to FISH and IgVH mutation status was evaluated. In total, 482 patients were analyzed, but evaluation of prognostic factors was restricted to 399 untreated cases. The prognostic significance of age, white blood cell (WBC) count, IgVH status, and TP53 and ATM deletions was confirmed. In addition, a prognostic impact of translocations involving the IGH@ locus (t(IgH)) and of a complex aberrant karyotype was found. On the basis of these results, we propose a scoring system for overall survival (OS) based on: age >or=65 years, WBC >or=20 x 10(9)/l, unmutated IgVH status, TP53 deletion, t(IgH), and the number of chromosome aberrations observed with CBA. Three risk groups showed considerable differences in OS (94.5% vs. 64.3% vs. 41.1% surviving at 5 years, P < 0.0001). Time to treatment (TTT) can be predicted best by unmutated IgVH status, ATM deletion, t(IgH), and number of chromosome aberrations. Four distinct subgroups were separated with median TTT of 110.7 months, 39.8 months, 19.5 months, and 3.8 months, respectively (P < 0.0001). In conclusion, cytogenetic data from CBA add prognostic information. The proposed scoring systems for OS and TTT based on a combination of genetic markers improve the separation of prognostic subgroups in CLL already early in the course of the disease.
Assuntos
Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Aberrações Cromossômicas , Leucemia Linfocítica Crônica de Células B/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular/genética , Bandeamento Cromossômico , Proteínas de Ligação a DNA/genética , Feminino , Deleção de Genes , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação/genética , Prognóstico , Proteínas Serina-Treonina Quinases/genética , Taxa de Sobrevida , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
The combination of bendamustine (B) and paclitaxel (P) as anthracycline-free treatment option in patients with advanced breast cancer has been evaluated in the previous RiTa I trial. The regimen of weekly B 70 mg/m(2) and P 90 mg/m(2) with a pause every 4th week was established as an effective regimen with low toxicity. The aim of the present RiTa II study was to investigate the potential of BP as anthracycline-free combination therapy. The primary objective was to determine the progression-free survival (PFS); secondary endpoints were safety, tolerability, overall response rate (ORR) and overall survival (OS). 26 patients were available, 15 received BP as first-line, 11 as beyond first-line treatment. 27% patients had triple-negative breast cancer (TNBC). Median PFS and OS were 7.3 months (95% confidence interval (CI): 5.5-10.9) and 14.9 months (95% CI: 9.9-22.9), respectively. The 1-year PFS rate was 20.3% and the 1-year OS rate 71.2%. The ORR was 42.3%, including 4 complete and 7 partial remissions. TNBC patients reached an ORR of 71.4%. Anthracycline-pretreated patients showed an ORR of 43.8%, confirming bendamustine's lack of cross-resistance to anthracycline agents. BP represents a favorable option with moderate toxicity in pretreated metastatic breast cancer and offers a possibility for application in anthracycline-pretreated and TNBC patients.