Diffuse Large B-Cell Lymphoma in the Public-Sector of Johannesburg, South Africa, in the Era of Widescale Antiretroviral Therapy Use

Vaughan, Jenifer; Perner, Yvonne; Wiggill, Tracey

doi:10.1097/qai.0000000000003069

Cited by 3 publications

(2 citation statements)

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“…Survival rates in this study were very much poorer than is typically reported in high income countries, a finding which we have documented previously [30]. Important contributors to this finding were late case presentation and/or aggressive disease, as over 40% of the patients who died did so within one month of diagnosis, with 20% dying before any chemotherapy could be administered.…”

Section: Discussioncontrasting

confidence: 46%

The prognostic impact of monocyte fluorescence, immunosuppressive monocytes and peripheral blood immune cell numbers in HIV-associated Diffuse Large B-cell Lymphoma

et al. 2023

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Introduction Diffuse large B-cell lymphoma (DLBCL) is a high grade non-Hodgkin lymphoma which is common among immunodeficient people. Derangements of peripheral blood immune cells have been described to have a prognostic impact in DLBCL in high income countries, including a monocytosis, the ratios of lymphocytes to both monocytes (L:M) and neutrophils (N:L), as well as the numbers of regulatory T-cells (Tregs) and immunosuppressive monocytes (HLA-DRlow monos). To date, the impact of these variables has not been assessed in the setting of HIV-associated DLBCL (HIV-DLBCL), which is among the most common malignancies seen in people living with HIV. In this study, we assessed these factors in a cohort of South African patients with DLBCL and a high HIV-seropositivity-rate. In addition, we evaluated the prognostic value of monocyte activation (as reflected by monocyte fluorescence (MO-Y) on a Sysmex haematology analyser). This parameter has to date not been assessed in the setting of DLBCL. Methods A full blood count and differential count as well as flow cytometry for HLA-DRlow monocyte and Treg enumeration were performed in patients with incident DLBCL referred to the Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa between November 2019 and May 2022. Additional clinical and laboratory data were recorded from the patient charts and laboratory information system. Results Seventy-six patients were included, of whom 81.3% were people living with HIV with a median CD4 count of 148 cells/ul. Most patients had advanced stage disease (74.8%) and were predominantly treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy (without Rituximab). At a median follow-up period of 19 months, the median survival time was 3.5 months, with a 12-month survival rate of 27.0%. All of the immune-cell-related variables (with the exception of the CD4 count) were similar between the people living with HIV and the HIV-negative individuals. In contrast to previous studies, a high monocyte count, the L:M and increased numbers of HLA-DRlow monocytes were not significantly associated with survival in HIV-DLBCL, while a neutrophilia (>8 x 109/L), the N:L (>6:1), high numbers of Tregs (≥5.17% of CD4s) and lymphopenia (<1.3 x 109/L) were. In addition, increased monocyte fluorescence (MO-Y >115.5) was associated with superior outcomes, which we speculate to reflect a more robust antitumour immune response among individuals with high levels of monocyte activation. On Cox Proportional hazard analysis, immune-cell factors independently associated with survival included a CD4 count <150 cells/ul and a neutrophilia. Conclusion The monocyte count, L:M and the number of HLA-DRlow monos are not strong prognostic indicators in HIV-DLBCL, while a low CD4 count and neutrophilia are. Elevation of the MO-Y shows some promise as a potential biomarker of antitumour immunity; further study in this regard would be of interest.

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Section: Discussioncontrasting

confidence: 46%

The prognostic impact of monocyte fluorescence, immunosuppressive monocytes and peripheral blood immune cell numbers in HIV-associated Diffuse Large B-cell Lymphoma

et al. 2023

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“…As we have reported previously ( Vaughan et al., 2022 ; Vaughan et al., 2023 ), survival rates in this cohort were poor as compared to those reported in high income countries (5 year survival rates over 60%) ( Sehn and Salles, 2021 ), as well as in two regional studies, one performed in Malawi among 86 adult patients with a HIV-seropositivity rate of 59% (2 year survival rate of 38%) ( Painschab et al., 2019 ), and the other in a South African study among 36 patients with HIV-DLBCL (2 year overall survival ~40%) ( de Witt et al., 2013 ). This was at least partially attributable to a very high early death rate (~30%), with over half of the patients who demised early doing so before they could be given chemotherapy.…”

Section: Discussionsupporting

confidence: 78%

Derangements of immunological proteins in HIV-associated diffuse large B-cell lymphoma: the frequency and prognostic impact

Vaughan,

Patel,

Suchard

et al. 2024

Front. Cell. Infect. Microbiol.

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IntroductionDiffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy of B-cells frequently encountered among people living with HIV. Immunological abnormalities are common in immunocompetent individuals with DLBCL, and are often associated with poorer outcomes. Currently, data on derangements of immunological proteins, such as cytokines and acute phase reactants, and their impact on outcomes in HIV-associated DLBCL (HIV-DLBCL) is lacking. This study assessed the levels and prognostic relevance of interleukin (IL)-6, IL-10 and Transforming Growth Factor Beta (TGFβ), the acute phase proteins C-reactive protein (CRP) and ferritin; serum free light chains (SFLC) (elevation of which reflects a prolonged pro-inflammatory state); and the activity of the immunosuppressive enzyme Indoleamine 2,3-dioxygenase (IDO)in South African patients with DLBCL.MethodsSeventy-six patients with incident DLBCL were enrolled, and peripheral blood IL-6, IL-10, TGFβ, SFLC and IDO-activity measured in selected patients. Additional clinical and laboratory findings (including ferritin and CRP) were recorded from the hospital records.ResultsSixty-one (80.3%) of the included patients were people living with HIV (median CD4-count = 148 cells/ul), and survival rates were poor (12-month survival rate 30.0%). The majority of the immunological proteins, except for TGFβ and ferritin, were significantly higher among the people living with HIV. Elevation of IL-6, SFLC and IDO-activity were not associated with survival in HIV-DLBCL, while raised IL-10, CRP, ferritin and TGFβ were. On multivariate analysis, immunological proteins associated with survival independently from the International Prognostic Index (IPI) included TGFβ, ferritin and IL-10.ConclusionDerangements of immunological proteins are common in HIV-DLBCL, and have a differential association with survival compared to that reported elsewhere. Elevation of TGFβ, IL-10 and ferritin were associated with survival independently from the IPI. In view of the poor survival rates in this cohort, investigation of the directed targeting of these cytokines would be of interest in our setting.

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Immune deficiency/dysregulation -associated lymphoproliferative disorders. Revised classification and management

Carbone,

Chadburn,

Gloghini

et al. 2024

Blood Reviews

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Diffuse Large B-Cell Lymphoma in the Public-Sector of Johannesburg, South Africa, in the Era of Widescale Antiretroviral Therapy Use

Cited by 3 publications

References 45 publications

The prognostic impact of monocyte fluorescence, immunosuppressive monocytes and peripheral blood immune cell numbers in HIV-associated Diffuse Large B-cell Lymphoma

The prognostic impact of monocyte fluorescence, immunosuppressive monocytes and peripheral blood immune cell numbers in HIV-associated Diffuse Large B-cell Lymphoma

Derangements of immunological proteins in HIV-associated diffuse large B-cell lymphoma: the frequency and prognostic impact

Immune deficiency/dysregulation -associated lymphoproliferative disorders. Revised classification and management

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