Treatment of large cell lymphoma in elderly patients with a mitoxantrone, cyclophosphamide, etoposide, and prednisone regimen: long-term follow-up results.

BACKGROUND: Patients with aggressive non-Hodgkin lymphoma (NHL) require intensive and extensive therapy, which seems impracticable in elderly patients due to hematologic and extrahematologic toxicity. Consequent dose reduction and therapy attenuation can reduce treatment-related toxicity but also decreases therapeutic efficacy. Thus, age represents a fundamental prognostic factor that has a profound influence on both therapeutic decisions and patient outcome. METHODS: Between January, 1990 and June, 1997, 145 patients age > 64 years (median age, 72.3 years) with a diagnosis of aggressive NHL were treated on a chemotherapy regimen that consisted of mitoxantrone, cyclophosphamide, etoposide, and prednisone. RESULTS: Ninety-one patients (63%) achieved complete remission, and 48 patients (33%) achieved partial remission, for an overall response rate of 96%. Six patients (4%) were resistant to therapy. The overall survival rate, with a median follow-up of 66 months, was 44%, and the failure free survival rate was 42%. The disease free survival rate was 63.5%, with a median follow-up of 60 months. Multivariate survival analysis showed that the achievement of complete remission was the single most important prognostic factor, which was associated significantly with longer survival (P < 0.0001). Toxicity was moderate, with 5 deaths (3%) due to complications related to therapy. CONCLUSIONS: The current results confirm that a protocol devised specifically for elderly patients may reduce toxicity and allow longer overall survival in this particular subset of patients.

Lyn kinase is activated following thrombopoietin stimulation of the megakaryocytic cell line B1647.

BACKGROUND AND OBJECTIVES: B1647 is a cell line derived from bone marrow cells of a patient with acute myeloid leukemia (M2) with a complete erythro-megakaryocytic phenotype and bears both k and p isoforms of c-mpl. Interestingly, spontaneous B1647 cell proliferation is significantly potentiated by thrombopoietin (TPO). DESIGN AND METHODS: We aimed to evaluate the proliferative signal transduction events following the activation of c-mpl and we stimulated B1647 cells with TPO 40 ng/mL for 3, 7, 15 and 30 minutes; cells were then lysed and whole lysates were immunoprecipitated with anti-phosphotyrosine antibodies. RESULTS: In our hands, TPO stimulation induced phosphorylation of several substrate proteins in B1647 cells. The increase in tyrosine phosphorylation from background spontaneous activation was transient, maximal after 10 minutes and declined to reach constitutive levels after 30 minutes. In particular, protein substrates between 50 and 140 kDa appeared to be selectively phosphorylated by TPO. We demonstrated that Jak2, Stat3 and Shc were activated in B1647 cells after TPO, as already shown for different cell lines by other authors. Moreover, Lyn kinase activation was detected. Grb2 co-immunoprecipitated with phosphorylated proteins. The phosphorylation of Syk kinase was not demonstrated, whereas Vav was activated by TPO. INTERPRETATION AND CONCLUSIONS: The pattern of protein phosphorylation determined in B1647 cells by TPO testifies the role of this cytokine in sustaining cell growth and indicates Lyn tyrosine kinase as a possible target protein in transduction of the TPO proliferative signal.