Machailo, J T2017-09-282017-09-282016http://hdl.handle.net/10539/23175A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfillment of the degree of Master of Medicine (Internal Medicine) Johannesburg, 2016Introduction: Non-Hodgkin Lymphoma (NHL) constitutes a heterogeneous group of lymphoproliferative disorders with a variable clinical and biological spectrum. Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of NHL and is the prototype of the aggressive lymphomas. DLBCL accounts for approximately one third of all newly diagnosed patients with NHL. Aim: The aim of the study was to review the demographic and clinical profile as well as the treatment and outcome of adult patients with DLBCL, at Chris Hani Baragwanath Academic Hospital (CHBAH). Furthermore, the study explored the impact of Human immunodeficiency virus (HIV) on the study population and compared the findings in both HIV seronegative and HIV seropositive patients, over a 5 year period (01/01/2008 to 31/12/2012). Methodology: This study entailed a retrospective review of all patients seen at CHBAH during the above time period, with a confirmed histological diagnosis of DLBCL. A data sheet was used to collect relevant information (demographics, clinical presentation, diagnostic tools, staging of the disease, prognostic factors and management) from the files of patients attending the Clinical Haematology unit, Department of Medicine, CHBAH. Results: A total of 139 evaluable patients were reviewed during the study period. The majority of patients were from the Gauteng province (83%), and of black African ethnicity (95%), in keeping with the patient demographics seen at CHBAH. There were 73 females (53%) and 66 males (47%) males, with a female: male ratio of 1.1:1. The median age of the patients was 41 years, with a range of 14-85 years. Common presenting features included constitutional symptoms (76%), extranodal disease (73%) and lymphadenopathy (64%). Most patients presented with advanced stage (III and IV) disease (76%). Human immunodeficiency virus (HIV) infection had a major impact on the study population, with 81% of the patients being HIV seropositive. HIV seropositive patients presented at a younger age of 39 years and had a female to male ratio of 1.04:1. A direct comparison between HIV seropositive and HIV seronegative individuals was less meaningful in this study, in view of the small number of HIV seronegative patients. However, adverse prognostic factors were consistently noted in the HIV seropositive patients, similar to the entire cohort (i.e. all the patients). In addition, tuberculosis was a comorbidity that was more strongly associated with HIV seropositivity. The median overall survival for all the patients in the study was 24 months. This generally poorer survival is attributed to significant delays in diagnosis and subsequent late referrals, late presentations with more advanced stage disease, more ‘B’ symptoms, more extranodal disease as well as the significant impact of HIV on NHL. HIV seropositive patients present with more aggressive histological subtypes (however, this study was specific to DLBCL and limited to DLBCL), atypical clinical and laboratory features, more frequent comorbidities such as tuberculosis and other opportunistic infections, more myelosuppression, delays in giving chemotherapy on schedule, and ultimately, a poorer prognosis. Conclusion: NHL is the most common haematological malignancy encountered in adults at CHBAH. DLBCL accounts for 35% of all the patients with NHL. HIV seropositivity is present in 81% of the patients with DLBCL and has a significant impact with regard to the presentation and outcome of the patients in our study. More recently, with the early introduction and continuation of combination antiretroviral treatment (cART), the institution of appropriate antibiotic and CNS prophylaxis, the more liberal use of growth factors and more optimal chemotherapy with the early introduction of etoposide and rituximab and the use of autologous stem cell transplantation in patients with relapsed, chemosensitive disease, it is hoped that the outcome of patients with DLBCL treated at CHBAH, will improve significantly compared to the outcome of the patients in this retrospective study.enThesis