Different variants of Burkitt lymphoma (BL) are being recognised by the 4th Edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, namely endemic, sporadic and immunodeficiency-related BL. All three variants differ in epidemiologic features and also in part in their molecular characteristics, but in turn show considerable biologic similarities. For example, a chromosomal translocation juxtaposing the MYC-gene nexto one of the immunoglobulin (IG) loci is the hallmark genetic alteration in all three subtypes. Secondary genetic alterations include somatic pathogenic variants in genes like MYC or TP53, genes encoding the TCF3/ID3 or SWI/SNF complexes or in cell cycle regulators like CCND3. Notably, the frequency of these aberrations varies with epidemiologic variant, but also at least in the sporadic variants with age. Explanatory for these differences could be that the frequency of mutations inversely correlates with presence of EBV in the tumor cells. Indeed, EBV positivity is associated with signficant alterations of the epigenome of BL cells, and e.g. altered DNA methylation might substitute for genomic mutations in BL. Finally, germline predisposition likely also contributes to BL pathogenesis, e.g. via modifying the risk for EBV infection or malaria. Basing on the wealth of recent whole genome, epigenome and transcriptome data pulbished by us and others and taking into account the clinical and epidemiologic characteristics of the BL variants as well as infectious agents we here will discuss a simplified model for BL which shows the option to link the pathogenesis of the three variants.

Globally, adding rituximab to chemotherapy backbone (R-CHOP) has been the primary therapeutic advance for diffuse large B-cell lymphoma (DLBCL) in the past two decades, yielding absolute increases in long-term overall survival of 10-20% compared to chemotherapy alone. Rituximab also improves outcomes in patients with HIV-associated DLBCL. Rituximab is currently included in the WHO Model List of Essential Medicines, and several biosimilar drugs, with equivalent pharmacokinetic, safety, and efficacy data to the proprietary drug, are commercially available worldwide. Despite the importance and availability of biosimilar drugs, rituximab remains unavailable in most public sector settings in sub-Saharan Africa because of cost. Additionally, there are no prospective data for rituximab focused on populations in sub-Saharan Africa, where HIV is prevalent, the supportive care infrastructure is weak, hematopoietic growth factors are often unavailable, and the burden of opportunistic infections is high. Using data from the first prospective clinical trial for treatment of DLBCL with rituximab in sub-Saharan Africa that was conducted at Kamuzu Central Hospital in Malawi, this presentation will demonstrate that a) curative upfront lymphoma treatment is feasible, safe, and efficacious in this region, and b) investments in such high-quality cancer care may be very prudent when short-term costs result in a normal life expectancy thereafter. These sorts of demonstrations will hopefully spur a treatment access movement across the region for cancer that is analogous to what has occurred for HIV.

Infections from Epstein-Barr virus (EBV), malaria and HIV can all contribute to causing childhood lymphoma in sub-Saharan Africa, in particular Burkitt’s Lymphoma (BL), Hodgkin’s lymphoma and diffuse large B-cell lymphoma. The treatment is widely available and free-of-charge in most sub-Saharan countries. However, currently, the majority of children either remain undiagnosed, present late to hospital, or are diagnosed late while in hospital. Alongside raising cancer awareness, strengthening histopathology services in three referral hospitals and performing health-economic analyses of different diagnostic approaches, a multidisciplinary team of researchers based in Oxford, Tanzania and Uganda with mentorship from Prof Anna Schuh have developed a method to identify children presenting with suspected lymphoma using DNA analysis from liquid biopsies, a simple blood test that measures circulating tumour DNA (ctDNA) to make the diagnosis of cancer specifically for the EBV-related lymphomas in sub-Saharan Africa. Plans to use liquid biopsies for other cancer screenings across Africa in the future are part of the programme’s sustainability plan.
In close collaboration with the Muhimbili University of Health and Allied Sciences (MUHAS), the team has equipped a DNA laboratory for local DNA sequencing, cloud-based data analysis and clinical data collection. Efforts are underway to build additional capacity for a DNA sequencing laboratory in Uganda, in partnership with the Ugandan Central Public Health Laboratory. The programme not only contributes to building in-country capacity to analyse ctDNA, but also helps create capacity for other genomic research and diagnostics for example of infectious or inherited diseases.
Prof Schuh will present a summary of the programme including preliminary data on the first 160 children recruited.