Burkitt lymphoma and diffuse large B-cell lymphoma – therapeutic strategies and pathogenetic mechanisms

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Burkitt lymphoma (BL) is a rare, aggressive disorder constituting 1% of all non-Hodgkin lymphoma. Diffuse large B-cell lymphoma (DLBCL) is more common, accounting for 30% of malignant lymphoma. Standard treatment for adult BL and for certain subgroups of patients with DLBCL remains to be defined due to paucity of randomised trials performed. The focus in this thesis lies on the effect of prognostic factors and treatment on outcome for patients with these two aggressive lymphomas, using unselected, population based patient cohorts.

In the first and second study, prognostic factors and efficacy of treatment regimens used for adult BL patients were investigated using data from the Swedish lymphoma registry (SLR) and Danish lymphoma registry (study two). Age was determined the most important predictor of adverse prognosis, and improvement in outcome during the study period was restricted to patients aged ≤65. Also, the superiority of high-intensive chemotherapy regimens compared to low-intensive treatment was confirmed, whereas the role of the monoclonal antibody rituximab remained undefined.

In the third study, the impact of dose-dense chemotherapy administration and addition of etoposide were evaluated for adult DLBCL patients, using data from a six-year period, collected from the SLR. Among all patients, there was no evidence of a difference in outcome between examined regimens. However, when restricted to patients ≤65, the addition of etoposide to the R-CHOP-14 regimen was associated with superior outcome.

In study number four, the frequency and potential clinical implications of expression of the transcription factor SOX11 in adult BL was investigated. SOX11 is aberrantly expressed in various hematopoietic and solid malignancies and appears to affect clinicopathological characteristics. Fourteen of 45 examined adult BL samples expressed SOX11 and its presence did not impact overall survival, in our material. In contrast, SOX11 knockdown in a BL cell line resulted in increased cellular proliferation, suggesting a potential growth regulatory role for SOX11 in BL.

Collectively, the studies included in this thesis provide real-world data regarding the effect on outcome of patient characteristics and treatment in adult BL and DLBCL. Although optimal treatment needs to be established in a randomised setting, this work emphasises the importance of high-intensive treatment and provides unselected, population based information on clinicopathological factors that affect outcome. Novel therapeutic strategies are warranted particularly for elderly patients, but will hopefully contribute to improve survival and decrease toxicity for all adult BL and DLBCL patients. Additionally, results presented in this thesis may possibly serve as comparative data for future population based studies.

Details

Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical and Health Sciences

Keywords

  • Burkitt Lymphoma, Chemotherapy, SOX11, Diffuse large B-cell lymphoma, Prognostic factors, Rituximab
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
Award date2016 Nov 18
Place of PublicationLund
Publisher
  • Lund University: Faculty of Medicine
Print ISBNs978-91-7619-324-2
Publication statusPublished - 2016
Publication categoryResearch

Bibliographic note

Defence details Date: 2016-11-18 Time: 13:00 Place: Lecture Hall, Radioterapy building, floor 3, Department of Oncology, Skåne University Hospital, Lund. External reviewer(s) Name: Chamuleau, Martine E.D. Title: associate professor Affiliation: VU University Medical Centre, Department of Haematology, Amsterdam, The Netherlands --- ISSN: 1652-8220 Lund University, Faculty of Medicine Doctoral Dissertation Series 2016:98

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