Diffuse large B-cell lymphoma in a South African cohort with a high HIV prevalence: an analysis by cell-oforigin, Epstein-Barr virus infection and survival

Introduction: Diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) is subdivided according to the cell-of-origin (COO) classification into germinal centre B-cell (GCB) and activated B-cell (ABC) subtypes, each with different molecular profiles and clinical behaviour. This study aims to describe the pattern of the COO subtypes, the proportion of Epstein-Barr virus (EBV) co-infection, and their influence on survival outcomes in a setting of high HIV prevalence. Materials and Methods: This retrospective cohort study included patients diagnosed with de novo DLBCL NOS at our tertiary academic centre in Cape Town, South Africa over a 14-year period. Immunohistochemical stains were performed for COO classification, according to the Hans algorithm. Tumour EBV co-infection was established by EBV-encoded ribonucleic acid in situ hybridisation (EBER-ISH) staining. The effect of the COO subtypes and EBV co-infection on overall survival were described by means of univariate, bivariate and multivariate analyses. Results: A total of 181 patients with DLBCL NOS were included, which comprised 131 HIV-uninfected and 50 HIV-infected patients. There was an equal distribution of GCB and ABC subtypes in the HIV-infected and HIV-uninfected groups. EBV co-infection was detected in 16% of the HIV-infected cases and in 7% of the HIV-uninfected cases (p=0.09). There was no significant difference in the incidence of EBV co-infection between the GCB and ABC subtypes (p=0.67). HIV-infected patients with CD4≥150 cells/mm3 had similar survival to HIV-uninfected patients (p=0.005). Multivariate regression analysis showed that in the HIVinfected group with marked immunosuppression (CD4 <150 cells/mm3), there was significantly poorer overall survival compared to the HIV-uninfected group (HR 2.4, 95% CI 1.3–4.1). There were no statistically significant differences in overall survival by DLBCL COO subtype. Conclusions: There was no difference in the proportion of DLBCL COO subtypes, regardless of HIV status. EBV co-infection was more common in the HIV-infected group, but less than described in the literature. Unexpectedly, there were no significant differences in survival outcomes between the GCB and ABC subtypes. Higher CD4 counts in the HIV-infected group had good survival outcomes, while lower CD4 counts predicted adverse survival outcomes. Further research is needed to explore the genetic mutational landscape of HIVassociated DLBCL.

Grantor

Department of Clinical Laboratory Sciences

Year dc:date.issued

2022

Author dc:creator

• Cassim, Sumaiya

Advisors dc:contributor.advisor

• Antel, Katherine
• Verburgh Estelle

• B-cell lymphoma
• DLBCL NOS
• HIV-infected
• HIV
• South Africa

Handle dc:identifier.uri

http://hdl.handle.net/11427/36418

OAI identifier oai:identifier

oai:open.uct.ac.za:11427/36418