Factores pronósticos biológicos y clínicos en el linfoma de células del manto
ENGLISH SUMMARY: "BIOLOGICAL AND CLINICAL PROGNOSTIC FACTORS IN MANTLE CELL LYMPHOMA" TEXT: Mantle cell lymphoma (MCL) is characterized by the presence of translocation t(11;14)(q13;q32), an aggressive clinical course and poor response to chemotherapy. Few data concerning drug-induced apoptosis in MCL have been reported. The aim of the first study that constitutes the present thesis was to analyze the mechanisms of drug-induced apoptosis in MCL. Four cell lines carrying the t(11;14) and primary cells of 10 patients with MCL were incubated in vitro with several drugs currently used in the treatment of lymphoproliferative disorders and drug-induced cell death was characterized. Our results support that MCL cells have functional apoptotic machinery but require the integrity of functional DNA-damage response genes for its activation. From a clinical standpoint, extranodal involvement is a well-known feature in patients with MCL. Relatively few studies to date have focused on the peripheral blood (PB) involvement and the incidence of leukemic expression in MCL varies highly in different studies. The objective of our second study was to analyze the incidence, and the biological and clinical significance of leukemic involvement in patients with MCL. We investigated the incidence of PB involvement by both morphologic and flow cytometry (FC) analyses. Clinical features, genetic abnormalities detected by comparative genomic hybridization (CGH) and patient outcome were also determined. Leukemic expression at diagnosis detected by FC was a highly common feature, even in patients with a normal lymphocyte count. Although morphologically apparent leukemic expression was not associated with specific chromosomal alterations detected by CGH, a lymphocyte count >/ 5 x 10(9)/L was correlated with particular genetic abnormalities and a poor outcome. The incidence of central nervous system (CNS) involvement in patients with MCL is also highly variable in different studies, and predicting factors and outcome of CNS infiltration in these patients have not been thoroughly investigated. The aim of our study was to assess the incidence and factors for CNS involvement in MCL. In addition, we analyzed the clinical features, therapy and outcome of patients with MCL once CNS infiltration was detected. Our results suggest that, in most cases, CNS involvement occur late in the course of the disease, as part of a generalized relapse or progression. Blastoid histology, high proliferative index, high serum LDH and high-risk IPI are the variables associated with a higher risk to develop this complication.
Document Full Text
Advisor:Bosch Albareda, Francesc
School:Universitat de Barcelona
Source Type:Master's Thesis
Date of Publication:01/25/2008