Regional Oncology Research Center (Stimulate Research in HIV/AIDS Supplement)

Johns Hopkins University, Baltimore MD

Investigators

Linked publications, trials & patents

Abstract

PROJECT SUMMARY Worldwide, Hodgkin lymphoma (HL) is treated with curative intent, regardless of HIV status. In South Africa, at least 40% of people living with HIV (PWH) with HL and marrow involvement do not survive until diagnosis. For those that survive long enough for a diagnosis to be pathologically confirmed, secondary hemophagocytic lymphohistiocytosis (HLH) appears to be a significant contributor to the high mortality and a cause of considerable morbidity resulting in poor outcomes. Strategies to improve the diagnosis of HL in this population are desperately needed. In a cohort of HIV-associated HL in South Africa, a marked elevation of ferritin was seen at time of diagnosis and was associated with known poor prognostic factors, raising the question as to whether a marked elevation of ferritin could be useful in prioritizing HL diagnosis in this setting. While HL is not the only trigger associated with HLH in Johannesburg (or an elevation in serum ferritin), it was associated with over 44% of suspected HLH cases referred to Hematology. Co-infection with TB in PWH and HL is also a considerable concern in South Africa, however one of the most widely used diagnostic tests for disseminated TB has only modest sensitivity (~50%). Having a biomarker that can help identify patients early for prioritized HL diagnosis could result in lives saved. Additionally, this biomarker could help identify patients at high risk for early mortality. Several future clinical trials could be considered for this population including: 1) Empiric TB treatment if ferritin is markedly elevated 2) Frontline clinical trial of immunotherapy to aid in the management of both HLH and HL 3) Incorporation of JAK-inhibitors (i.e. Ruxolitinib) into the upfront treatment regimen to help manage co-existing HLH. We acknowledge the drawbacks of ferritin given that it is a non-specific marker of inflammation. The benefit of serum ferritin is that it is readily available in low resource settings. In this proposal, by utilizing data from an existing cohort of lymphoma patients and stored specimens from a pneumonia cohort study, we will better understand the levels of ferritin elevation seen in other subtypes of lymphoma, other EBV-associated tumors, PWH and disseminated TB and PWH admitted to the hospital with pneumonia. Our overarching goal is to show that extreme elevations in ferritin, that do not respond to initial treatment regimens (i.e antibiotics or TB therapy), should raise the suspicion of HL in PWH.