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Title: Epidemiology, prognosis and treatment of aggressive non-Hodgkin lymphomas
Authors: Sieniawski, Michal Konrad
Issue Date: 2017
Publisher: Newcastle University
Abstract: The concept of aggressive non-Hodgkin lymphoma (NHL) originates in the Working Formulation classification of NHL and describes a heterogeneous group of NHLs. Despite the introduction of the WHO classification the term ‘aggressive non- Hodgkin lymphoma’ still remains in clinical use. This work will focus on some important aspects of epidemiology, clinical presentation, prognosis, treatment and treatment outcome in two main subtypes of aggressive lymphoma: diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL). DLBCL is the most common NHL occurring more frequently in older patients and is characterised by heterogeneous histology. The current standard treatment is immunochemotherapy with cyclophosphamide, doxorubicine, vincristine, prednisone (CHOP) and anti-CD20 antibody rituximab. Approximately 50-60% of patients eventually die from DLBCL. Depending on the patient’s age, two different approaches can be defined in order to improve the outcome in DLBCL. In younger patients, the better risk stratification and prediction of response to standard therapy can help to define the high-risk groups suitable for new, more intensive therapy approaches. In elderly patients, where already delivery of standard chemotherapy is difficult, the introduction of the targeted therapies and its combination with new less toxic chemotherapy regimens could be seen as a future approach. Targeted therapies can be also adopted in younger patients. It was aimed to describe DLBCL in a population-based setting in order to obtain the realistic picture of disease, define the needs of patients and develop a prognostic model based on expression of molecular factors in routine formalin fixed paraffin embedded (FFPE) tissue samples using quantitative polymerase chain reaction (qPCR) for identification of high risk patients. A population-based study on 1863 DLBCL patients described picture of disease, therapy and outcome. Importantly, it revealed that a significant number of patients (30%) who did not receive standard chemotherapy were characterised by a very bad prognosis. Additionally, the duration of first remission was one of the most important factors for patient survival, suggesting first-line treatment should be escalated in suitable high-risk patients. The model based on expression of MYC, HLA-DRΒ and variant 2 of the C13orf25 locus (v2-transcript) using qPCR was successfully established in FFPE tissue. Unfortunately, we could not confirm its predictive value in patient cohort. The preliminary work on expression of microRNA encoded in v2-transcript as predictive biomarker was performed in FFPE tissue and delivered promising results. PTCL is characterised by dismal outcome when treated with standard CHOP. The rarity and heterogeneity of the PTCL, lack of prospective trials in homogenous types of the PTCL as well as hesitation to use high intensity treatments can contribute to the poor outcome. It was aimed to collect prospective data in a population-based setting on clinical presentation, treatment and outcome of patients with enteropathy associated T-cell lymphoma (EATL), a subtype of PTCL, and to assess the role of a novel high-dose chemotherapy with ifosfamide, epirubicin, etoposide/methotrexate and autologous stem cell transplantation (IVE/MTX-ASCT) in EATL and other PTCL subtypes. The incidence of EATL in the studied population was 0.14/100 000 per year. The detailed picture of the disease at presentation was obtained. The prognosis was dismal when treated with conventional treatment with 5-years PFS and OS of 18% and 20%, respectively. The new IVE/MTX–ASCT regimen improved the patient outcome with the 5-years PFS and OS of 52% and 60%, respectively. The results of IVE/MTXASCT in other PTCL were also promising with 3-years PFS and OS of 65% and 72%, respectively.
Description: PhD Thesis
Appears in Collections:Northern Institute for Cancer Research

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