RESUMO
The expression of zeta-associated protein 70 (ZAP-70) in chronic lymphocytic leukemia (CLL) seems to correlate with the mutational status of the immunoglobulin heavy-chain variable-region genes, clinical course and patient prognosis. The aim was to determine the prognostic significance of the immunohistochemical expression of ZAP-70 protein in CLL by means of the long-term follow-up of 108 patients. This study identified 3 patterns of ZAP-70 immunoreactivity: negative (58 patients, 54%), weakly positive (20 patients, 18%) and strongly positive (30 patients, 28%). Overall, ZAP-70 immunoreactivity correlated with an abnormal karyotype ( p = 0.017), a lymphocyte doubling time (LDT) of <6 months ( p = 0.001) and <12 months ( p = 0.01), Rai II - IV and Binet B - C stage ( p = 0.013), the clinical need for chemotherapy ( p < 0.001) and the need for more than 1 chemotherapy line ( p < 0.001). Kaplan-Meier analysis demonstrated that ZAP-70 immunoreactivity closely correlated with a shorter LDT ( p < 0.0001) and time from diagnosis to initial therapy ( p = 0.0001). The same significance was retained when the patients were stratified into the ZAP-70 immunoreactivity groups ( p < 0.0001). This study shows that ZAP-70 immunoreactivity can be a reliable prognostic marker in CLL and proposes a system for evaluating the results. The observations support the inclusion of the immunohistochemical expression of ZAP-70 in clinical trials involving CLL patients.
Assuntos
Leucemia Linfocítica Crônica de Células B/metabolismo , Proteína-Tirosina Quinase ZAP-70/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Citogenética , Progressão da Doença , Seguimentos , Humanos , Imuno-Histoquímica , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Proteína-Tirosina Quinase ZAP-70/análiseRESUMO
Subcutaneous low-dose alemtuzumab (10 mg t.i.w. for 18 weeks) induced a 50% response rate, including 25% complete response, in 16 patients with refractory chronic lymphocytic leukemia (CLL) patients. The responses were substantial even in patients with unfavorable cytogenetics, fludarabine/rituximab refractoriness, Rai stage IV, previous infections, and age over 65 years. Subcutaneous low-dose alemtuzumab is effective in poor prognosis B-CLL, and has a particularly favourable toxicity profile.