Aggressive lymphomas

ArticleinLa Revue du praticien 52(9):972-7 · June 2002with12 Reads
DOI: 10.1056/NEJMra0807082 · Source: PubMed
Treatment strategies of aggressive lymphoma are the subject of this review. Main regimens of chemotherapy are described, as well as prognostic factors that direct therapeutic decisions. First-line treatment modalities of localized and advanced disease are envisaged, including the role of high-dose therapy with hematopoietic support, as well as salvage treatment of failures. Finally, the recent and major impact of immunotherapy based on the CD20 monoclonal antibody is outlined.
    • "Many of the cytotoxic drugs used to treat DLBCL induce caspase-dependent apoptosis, however, a significant number of patients acquire resistance that is associated with defective caspase-dependent apoptotic pathways (3). Upregulation of the BCL2 gene, due to either the t(14;18) translocation or genomic BCL2 gain/amplification, results in overexpression of the Bcl-2 protein and apoptosis resistance (2). The Bcl-2 family is a group of mitochondrial-associated proteins that are characterized as either anti-apoptotic or pro-apoptotic. "
    [Show abstract] [Hide abstract] ABSTRACT: Bcl-2 and other anti-apoptotic proteins are associated with defective caspase-dependent apoptotic pathways, resulting in chemoresistance. We have previously shown that ATN-224, a copper chelator drug, induces cell death in murine thymic lymphoma cells transfected with Bcl-2. In the current study, we tested whether ATN-224 was effective in diffuse large B cell lymphoma (DLBCL) cells, which have increased anti‑apoptotic proteins through translocation or amplification. We found that nanomolar concentrations of ATN-224 induced cell death in DLBCL cells independent of Bcl-2, Bcl-xL or Mcl-1 status. ATN-224 treatment resulted in mitochondrial dysfunction, release of apoptosis-inducing factor (AIF) and induction of caspase‑independent cell death. In addition, ATN-224 degraded Mcl-1 and enhanced the effect of the BH3 mimetic ABT-263. These findings indicate that ATN-224 has potential as a therapeutic for the treatment of DLBCL. Induction of caspase‑independent cell death in apoptosis‑resistant DLBCL would provide a therapeutic alternative for the treatment of refractory disease.
    Full-text · Article · Apr 2014
    • "Genome-wide molecular profiling has revealed a high degree of complexity in DLBCL,and significantly accelerated the understanding of oncogenic mechanisms in lymphomagenesis [6], [7]. On the basis of gene expression profiling (GEP), DLBCL is classified into distinct molecular subtypes [8]–[11]. "
    [Show abstract] [Hide abstract] ABSTRACT: Despite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL. We analysed 51 prospectively collected pretreatment tumour samples from clinically high risk patients treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis with high resolution array comparative genomic hybridization (aCGH) and gene expression microarrays. Major finding was validated at the protein level immunohistochemically in a trial specific tissue microarray series of 70, and in an independent validation series of 146 patients. We identified 31 genes whose expression changes were strongly associated with copy number aberrations. In addition, gains of chromosomes 2p15 and 18q12.2 were associated with unfavourable survival. The 2p15 aberration harboured COMMD1 gene, whose expression had a significant adverse prognostic impact on survival. Immunohistochemical analysis of COMMD1 expression in two series confirmed the association of COMMD1 expression with poor prognosis. COMMD1 is a potential novel prognostic factor in DLBCLs. The results highlight the value of integrated comprehensive analysis to identify prognostic markers and genetic driver events not previously implicated in DLBCL. NCT01502982.
    Full-text · Article · Mar 2014
    • "These differ in the postulated stage of cell of origin, gene expression, and response to anthracycline-based chemotherapy. The GCB DLBCL has better response rate than ABC DLBCL.[45] "
    [Show abstract] [Hide abstract] ABSTRACT: Relapsed-Refractory Diffuse Large B Cell Lymphoma (RR DLBCL), which accounts for approximately one-third of patients with DLBCL, remains a major cause of morbidity and mortality. Managing RR DLBCL continues to be a challenge to the treating hemato-oncologist. Salvage high-dose chemotherapy followed by autologous stem cell transplantation is the standard of care for chemosensitive relapses in DLBCL. Various salvage regimens are available, but the quest for an optimal regimen continues. The addition of rituximab to the salvage regimen has improved the outcome of RR DLBCL. Several pertinent issues regarding the management of RR DLBCL are discussed in this short review.
    Article · Mar 2014
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