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HIV-associated Burkitt lymphoma: outcomes from a US-UK collaborative analysis.

ABSTRACT: Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) patients with HIV-BL treated from 2008 to 2019 aiming to identify prognostic factors and outcomes. With a median follow up of 4.5 years, the 3-year progression-free survival (PFS) and overall survival (OS) were 61% (95% confidence interval [CI] 55% to 67%) and 66% (95%CI 59% to 71%), respectively, with similar results in both countries. Patients with baseline central nervous system (CNS) involvement had shorter 3-year PFS (36%) compared to patients without CNS involvement (69%; P < .001) independent of frontline treatment. The incidence of CNS recurrence at 3 years across all treatments was 11% with a higher incidence observed after dose-adjusted infusional etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide (DA-EPOCH) (subdistribution hazard ratio: 2.52; P = .03 vs other regimens) without difference by CD4 count 100/mm3. In multivariate models, factors independently associated with inferior PFS were Eastern Cooperative Oncology Group (ECOG) performance status 2-4 (hazard ratio [HR] 1.87; P = .007), baseline CNS involvement (HR 1.70; P = .023), lactate dehydrogenase >5 upper limit of normal (HR 2.09; P < .001); and >1 extranodal sites (HR 1.58; P = .043). The same variables were significant in multivariate models for OS. Adjusting for these prognostic factors, treatment with cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) was associated with longer PFS (adjusted HR [aHR] 0.45; P = .005) and OS (aHR 0.44; P = .007). Remarkably, HIV features no longer influence prognosis in contemporaneously treated HIV-BL.

SUBMITTER: Alderuccio JP

PROVIDER: S-EPMC8341354 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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HIV-associated Burkitt lymphoma: outcomes from a US-UK collaborative analysis.

Alderuccio Juan Pablo JP Olszewski Adam J AJ Evens Andrew M AM Collins Graham P GP Danilov Alexey V AV Bower Mark M Jagadeesh Deepa D Zhu Catherine C Sperling Amy A Kim Seo-Hyun SH Vaca Ryan R Wei Catherine C Sundaram Suchitra S Reddy Nishitha N Dalla Pria Alessia A D'Angelo Christopher C Farooq Umar U Bond David A DA Berg Stephanie S Churnetski Michael C MC Godara Amandeep A Khan Nadia N Choi Yun Kyong YK Kassam Shireen S Yazdy Maryam M Rabinovich Emma E Post Frank A FA Varma Gaurav G Karmali Reem R Burkart Madelyn M Martin Peter P Ren Albert A Chauhan Ayushi A Diefenbach Catherine C Straker-Edwards Allandria A Klein Andreas A Blum Kristie A KA Boughan Kirsten Marie KM Mian Agrima A Haverkos Bradley M BM Orellana-Noia Victor M VM Kenkre Vaishalee P VP Zayac Adam A Maliske Seth M SM Epperla Narendranath N Caimi Paolo P Smith Scott E SE Kamdar Manali M Venugopal Parameswaran P Feldman Tatyana A TA Rector Daniel D Smith Stephen D SD Stadnik Andrzej A Portell Craig A CA Lin Yong Y Naik Seema S Montoto Silvia S Lossos Izidore S IS Cwynarski Kate K

Blood advances 20210701 14

Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) patients with HIV-BL treated from 2008 to 2019 aiming to identify prognostic factors and outcomes. With a median follow up of 4.5 years, the 3-year progression-free survival (PFS) and overall survival (OS) were 61% (95% confidence interval [CI] 55% to 67%) and 66% (95%CI 59% to 71%), respectiv ...[more]

PMID: 34283175

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Project description:Deficiencies in Epstein-Barr virus (EBV)-specific T cell immunosurveillance appear to precede the development of endemic Burkitt lymphoma (eBL), a malaria-associated pediatric cancer common in sub-Saharan Africa. However, T cell contributions to eBL disease progression and survival have not been characterized. Our objective was to investigate regulatory and inflammatory T cell responses in eBL patients associated with clinical outcomes. By multi-parameter flow cytometry, we examined peripheral blood mononuclear cells from 38 eBL patients enrolled in a prospective cohort study in Kisumu, Kenya from 2008-2010, and 14 healthy age-matched Kenyan controls. Children diagnosed with eBL were prospectively followed and outcomes categorized as 2-year event-free survivors, cases of relapses, or those who died. At the time of diagnosis, eBL children with higher CD25+Foxp3+ regulatory T (Treg) cell frequencies were less likely to survive than patients with lower Treg frequencies (p = 0·0194). Non-survivors also had higher absolute counts of CD45RA+Foxp3lo naïve and CD45RA-Foxp3hi effector Treg subsets compared to survivors and healthy controls. Once patients went into clinical remission, Treg frequencies remained low in event-free survivors. Patients who relapsed, however, showed elevated Treg frequencies months prior to their adverse event. Neither concurrent peripheral blood EBV load nor malaria infection could explain higher Treg cell frequencies. CD8+ T cell PD-1 expression was elevated in all eBL patients at time of diagnosis, but relapse patients tended to have persistently high PD-1 expression compared to long-term survivors. Non-survivors produced more CD4+ T-cell IL-10 in response to both Epstein-Barr Nuclear Antigen-1 (EBNA-1) (p = 0·026) and the malaria antigen Plasmodium falciparum Schizont Egress Antigen-1 (p = 0·0158) compared to survivors, and were concurrently deficient in (EBNA-1)-specific CD8+ T-cell derived IFN-γ production (p = 0·002). In addition, we identified the presence of Foxp3-IL10+ regulatory Type 1 cells responding to EBNA-1 in contrast to the malaria antigen tested. These novel findings suggest that poor outcomes in eBL patients are associated with a predominantly immuno-regulatory environment. Therefore, Treg frequencies could be a predictive biomarker of disease progression and manipulation of Treg activity has potential as a therapeutic target to improve eBL survival.

Dataset Information

HIV-associated Burkitt lymphoma: outcomes from a US-UK collaborative analysis.

Publications

HIV-associated Burkitt lymphoma: outcomes from a US-UK collaborative analysis.

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