Follicular and Diffuse Large B-Cell Lymphoma - Studies of Primary Treatment and Prognostic Factors

The most common types of B-cell lymphoma are diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), which together make up 50% of all NHL (non-Hodgkin’s lymphomas). DLBCL has a multifactorial aetiology. Patients with DLBCL are cured in approximately 50% of cases with adequate chemotherapy. FL is an indolent and usually incurable disease, and many different therapeutic approaches are used to maintain a good quality of life for a prolonged time. Data were obtained from the Swedish Lymphoma Registry and used to investigate prognostic factors, incidence, and treatment modalities of the population with DLBCL and FL in Sweden. The first study demonstrated an increased incidence of DLBCL during the period 2000-2010, especially among men. Extranodal involvement of bone marrow, the central nervous system, lung, and bone was associated with inferior outcome, and male sex also had a negative impact on overall survival (OS). The OS of DLBCL patients has improved markedly during the past decade, most prominently in the age group 60-78 years, and in patients with good performance status. No significant improvement was seen in OS in patients with poor PS or in patients older than 78 years, indicating that attention should be directed towards high-risk patients and elderly patients, who may require specially tailored treatment. In the second study, the efficacy of three chemotherapy regimens was evaluated in terms of the OS of DLBCL patients. The addition of etoposide to primary chemotherapy was found to be associated with improved survival in DLBCL patients up to 65 years of age, when corrected for prognistic factors, indicating that this may be an effective treatment option for this patient population. In the third study, the season of diagnosis was found to affect OS in male patients with DLBCL, showing improved survival of patients diagnosed during the summer months. Possible explanations of these results may be the higher vitamin D levels during this period and/or the immunomodulatory effects of sunlight. In the final study, the initial management of FL was investigated by comparing the efficacy of different treatment options. The OS of the patients managed with the watch-and-wait approach was not significantly different from that of patients treated immediately. Patients treated with single-agent rituximab had a similar OS to patients treated with chemoimmunotherapy. The studies described in this thesis were performed using population-based datasets, and the results contribute to previously reported findings on prognostic factors and the improvement of OS of patients with DLBCL over the past decade. The improved outcome of DLBCL patients under 65 years of age with etoposide addition suggests a beneficial effect of this strategy. Elderly patients and patients with high-risk factors are in need of customized and more aggressive treatment including novel agents. For the optimal management of patients with FL, the watch-andwait strategy and rituximab monotherapy should both be considered as first-line treatment options. Vitamin D, activated by sunlight, could play an important role in immunomodulation and the enhancement of the effect of chemoimmunotherapy.