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Summary Background There are no clinical trials involving patients with diffuse large B-cell lymphoma (DLBCL) in sub-Saharan Africa since antiretroviral therapy (ART) for HIV became widely available in this region. We aimed to establish the safety and efficacy of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with DLBCL in Malawi. Methods This prospective, single-arm, non-randomised phase 1/2 clinical trial was done at Kamuzu Central Hospital Cancer Clinic (Lilongwe, Malawi). Eligible patients were adults (aged 18–60 years) with newly diagnosed DLBCL, an Eastern Cooperative Oncology Group performance status of 0–2, a CD4 count of 100 cells per μL or higher (if HIV-positive), measurable disease by physical examination, an absolute neutrophil count of 1000 × 109 cells per L or higher, a platelet count of 100 × 109 platelets per L or higher, a serum creatinine concentration of 132·60 μmol/L or less, a total bilirubin concentration of 34·21 μmol/L or less, a negative urine pregnancy test in women of childbearing potential, and no previous cytotoxic therapy. Pregnant or breastfeeding women, and individuals with CNS involvement from DLBCL, chronic hepatitis B infection (unless they were receiving tenofovir plus lamivudine), or any other comorbidities that would compromise the protocol objectives were excluded. Eligible patients received intravenous rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 (maximum 2 mg/m2), and oral prednisone 100 mg or an equivalent drug every 21 days for up to six cycles. HIV-positive patients received concurrent ART. The primary outcome was the proportion of patients with National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or 4 non-haematological toxic effects or treatment-related deaths after six cycles of treatment. Secondary efficacy outcomes included the proportion of patients with a complete response after six cycles of treatment, and progression-free survival and overall survival at 12 months and 24 months. This trial is registered with ClinicalTrials.gov , NCT02660710 . Findings Between Aug 1, 2016, and July 31, 2019, 76 patients were screened, of whom 37 were eligible for the study and received R-CHOP. The median age of patients was 44 years (IQR 39–49) and 16 (43%) were women. Of all 37 patients, 20 (54%) had stage III or IV DLBCL, and the age-adjusted international prognostic index was 2 or higher in 25 (68%) patients. 27 (73%) patients were HIV-positive, with a median CD4 count of 208 cells per μL (IQR 144–422), and 21 (78%) patients were receiving ART at enrolment. Patients completed a median of six cycles (IQR 4–6). Grade 3 or 4 non-haematological toxic effects were reported in 12 (32% [95% CI 19–49]) patients, the most common of which was infection (nine [24%] patients). Of 16 (43%) deaths, ten were due to progression of DLBCL, four were due to treatment-related complications, and two were due to other causes, yielding a treatment-related mortality of 11% (95% CI 4–26%). Grade 3 or 4 neutropenia was observed in 26 (70%) patients, and grade 3 or 4 anaemia was observed in 11 (29%) patients. A total of 22 (59%) patients had a complete response. Overall survival was 68% (95% CI 50–80) at 12 months and 55% (37–70) at 24 months, and progression-free survival was 59% (42–73) at 12 months and 53% (35–68) at 24 months. Interpretation R-CHOP could be feasible, safe, and efficacious in patients with DLBCL in Malawi. This is the first completed clinical trial on DLBCL focused on sub-Saharan African populations. Given the paucity of data on treatment of DLBCL from this region, these results could inform emerging cancer treatment programmes in sub-Saharan Africa. Funding The University of North Carolina Lineberger Comprehensive Cancer Center.

Follicular lymphoma (FL) is an indolent, mature B-cell neoplasm classically characterised by the t(14;18)(q32;q21) with constitutive overexpression of the anti-apoptotic protein, BCL2. Most cases present in older adults with slowly progressive lymphadenopathy and follow an indolent clinical course. Typical morphology shows an expansile follicular proliferation with tumour expression of germinal centre markers, and bone marrow involvement at diagnosis is frequent. However, in the recent past, efforts to understand the biological and clinical heterogeneity of FL has effected significant change to the diagnostic approach. While morphological grade, assessed by enumerating large 'centroblasts' in the neoplastic follicles, generally correlates with outcome in systemic nodal FL, variants with high-grade morphology but indolent clinical behaviour have been identified. Given the clinical implications of these FL variants, knowledge of their clinical and histopathological defining features is of paramount importance to the pathologist. Furthermore, as with many areas of diagnostic oncology, precursors to FL have been identified and described with measurable rates of progression to bona fide lymphoma. Accurate diagnosis of these early lesions can often prevent unnecessary therapy and guide appropriate monitoring for disease progression. This review aims to summarise these key pathological and diagnostic features of FL. We further highlight the biological underpinnings of FL that will likely affect the classification, diagnosis, and treatment of patients with lymphoma.

Aggressive non‐Hodgkin lymphoma (NHL) is among the most common cancers in sub‐Saharan Africa (SSA), where CHOP is standard treatment and outcomes are poor. To address this, we treated 17 newly diagnosed adult patients in Malawi with Burkitt (n = 8), plasmablastic (n = 8), and primary effusion lymphoma (n = 1) with a modified EPOCH regimen between 2016 and 2019. Twelve patients (71%) were male and the median age was 40 years (range 16‐63). Eleven (65%) were HIV infected, median CD4 count was 218 cells/µL (range 9‐460), and nine (82%) had suppressed HIV RNA, We evaluated the safety and efficacy of EPOCH, with modifications as required for local administration, for patients with high‐risk NHL in Malawi. We treated 17 newly diagnosed adult patients in Malawi with Burkitt (n = 8), plasmablastic (n = 8), and primary effusion lymphoma (n = 1) with a modified EPOCH regimen between 2016 and 2019. Our experience suggests that EPOCH with setting‐appropriate modifications may be a practical, safe, and effective option for improving high‐risk NHL outcomes in Malawi and comparable settings, which deserves further prospective evaluation.

Highlights • Angiosarcoma is a rare endothelial malignancy associated with radiation exposure. • Very rarely, angiosarcoma has been reported to arise in the uterine cervix. • We report the first case of post-radiation angiosarcoma of the cervix.

Purpose: In 2016, Malawi implemented a universal test and treat (UTT) policy, expanding eligibility for antiretroviral therapy (ART) to anyone with confirmed HIV infection. Prior to 2016, Malawi restricted ART initiation to HIV-positive individuals with CD4 count ≤500 cells/µL, with WHO staging ≥III who were pregnant or breastfeeding, or who were younger than 5 years old. Here, we assess the impact on distribution of lymphoma presentation and baseline clinical characteristics at Kamuzu Central Hospital, Lilongwe, Malawi. Methods: Participants with newly diagnosed, pathologically confirmed lymphoproliferative disorders were enrolled from 2013 - 2020. We categorized participants as pre-universal ART (pre-UART) if enrolled during 2013-June 2016 or post-universal ART (post-UART) if enrolled during July 2016-2020 and evaluated clinical characteristics. Findings: Of 412 total participants, 156 were pre-UART and 256 were post-UART. The most common diagnoses were diffuse large B-cell lymphoma (DLBCL) (45%), low-grade lymphoma (11%), Burkitt lymphoma (10%), Hodgkin lymphoma (9%), and multicentric Castleman disease (7%) and there was no significant difference in distribution of diagnoses between pre-UART and post-UART periods (Figure 1). HIV prevalence was 50%, mean age 43, and 62% male. Sixty-six percent (48/73) of pre-UART HIV-positive participants knew their HIV status, for median 5 years (IQR 2-8) and 71% (41/58) were on ART for median 4 years (IQR 2-7). Eighty percent (94/117) of post-UART HIV positive participants knew their HIV status (p=0.02), for median 4 years (IQR 2-9) and 84% (89/106) were on ART (p=0.05) for median 4 years (IQR 2-8). HIV was suppressed Interpretation: There were no significant differences in lymphoma subtypes diagnosed or in traditional DLBCL prognostic factors after implementation of universal ART in Malawi. However, HIV was better controlled in the post-UART period and differences in immunological status may have implications for therapy and prognosis. Strengths of this study include a deeply characterized cohort, both clinically and pathologically. As opposed to epidemiological data from the US and Europe, we did not see a major shift in diagnoses over this time period with increasing access to ART. However, possible explanations for the differences include that this is not a epidemiological survey as cancer registration data is not comprehensively collected in Malawi and that the roll out of ART across sub-Saharan Africa has been much more gradual than the abrupt increase in access that was seen in the US and Europe. Therefore, epidemiological chances may also be more gradual. In summary, this is some of the most comprehensive data on lymphoma presentation from sub-Saharan Africa across periods of increasing access to ART and despite improved HIV control among incident lymphoma cases, there was no change in the distribution of diagnoses in this time period. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background and aims Updated diagnostic guidelines for eosinophilic esophagitis (EoE) have eliminated the requirement for a proton pump inhibitor (PPI) trial, but there are no models to identify patients with EoE based on these new criteria. We aimed to develop a predictive model for diagnosis of EoE based on the updated EoE diagnostic guidelines. Methods We performed a secondary analysis of a prospective study of adult patients referred for outpatient esophagogastroduodenoscopy at University of North Carolina who had symptoms of esophageal dysfunction; patients with prevalent EoE were excluded. We analyzed data from 206 EoE cases (mean age 40.1, 62.6% male, 93.2% white) and 306 controls (mean age 52.3, 37.9% male, 79.7% white). We built predictive models for case-control status, using clinical, endoscopic, and histologic features, and defining EoE by either the new or historical definition of PPI non-response. Model discrimination was assessed by the area under the receiver-operator characteristic curve (AUC). Results Before endoscopy, younger age, male sex, history of atopic condition or food allergy, and dysphagia identified patients with EoE with an AUC of 0.83. When we included endoscopy findings suggestive of EoE, the model identified patients with EoE with an AUC of 0.92; this increased to 0.99 when histology was included. Conclusion We developed a model to identify patients with EoE, without a trial of PPIs, based on updated diagnostic guidelines. Clinical features and endoscopic findings identified patients with EoE with an AUC of 0.92—even without histologic data and in the absence of dysphagia. This model can be used to select patients with upper gastrointestinal symptoms but without dysphagia for early diagnostic endoscopy. The model can also be used to identify cases of EoE when eosinophil counts are greater than 15 in biopsies but other causes of esophageal eosinophilia cannot necessarily be excluded.

Orbital lymphoma can result in rapid loss of vision if not diagnosed and treated in a timely manner. This patient presented with rapid visual loss and on examination had a rubeosis iridis with a hyphema as well as neovascular glaucoma with vitreous hemorrhage. His medical history included systemic diffuse large B-cell lymphoma and a workup ultimately revealed an orbital mass in the body of the optic nerve. Optic nerve biopsy demonstrated diffuse large B-cell lymphoma. To the authors' knowledge, neovascular glaucoma as the presentation of an extraocular diffuse large B-cell lymphoma has not been reported previously. Lymphomas of the orbit and its adnexa constitute roughly 1% of all non-Hodgkin lymphoma. Most cases are marginal-zone B-cell lymphomas, with the second most common being diffuse large B-cell lymphomas. Orbital lymphomas can rapidly progress to complete visual loss when not diagnosed early. The authors report a patient who presented with rapid visual loss due to hyphema, rubeosis iridis, neovascular glaucoma and vitreous hemorrhage secondary to orbital diffuse large B-cell lymphoma. Research methods were adherent to the ethical principles outlined in the Declaration of Helsinki as amended in 2013. The collection and evaluation of protected patient health information was Health Insurance Portability and Accountability Act compliant.The authors report a case of lymphoma metastatic to the optic nerve masquerading as neovascular glaucoma with vitreous hemorrhage.

Background Peripheral and mucosal eosinophilia may be associated with more aggressive disease in inflammatory bowel disease (IBD) patients. Vedolizumab blocks T lymphocytes, eosinophil adhesion, and extravasation in the gastrointestinal tract. It is not known if mucosal eosinophilia is a predictor for the therapeutic efficacy of vedolizumab. Methods This was a retrospective cohort study of IBD patients with ileal or colonic biopsies who were off steroids before starting vedolizumab. Biopsies were rereviewed by pathologists, and mean eosinophil density was quantified. Patient characteristics and steroid-free clinical response 6 months after beginning vedolizumab were determined. Features were compared between nonresponders and responders, and multivariable logistic regression was performed to identify predictors of clinical response. Results Of 251 IBD patients starting vedolizumab therapy, 65 patients (48% Crohn’s disease, 52% ulcerative colitis) met inclusion criteria. All IBD patients not responding to vedolizumab were more likely to have a higher baseline mean eosinophil count (340 ± 156 vs 236 ± 124; P = 0.004), be previously exposed to an anti-TNF (96% vs 56%; P = 0.001), and be male (58% vs 28%; P = 0.02). Mean eosinophil counts were significantly increased in colonic biopsies in UC nonresponders (438 ± 149 vs 299 ± 145; P = 0.01). A similar trend was seen in CD nonresponders. On multivariable analysis, colonic eosinophil density and prior anti-TNF exposure—and the combination of both—were independent predictors of response. Conclusion In ulcerative colitis, colonic eosinophilia and prior anti-TNF exposure were independent predictors of 6-month clinical nonresponse to vedolizumab. Mucosal eosinophil density as a novel biomarker should be explored in larger patient cohorts. Aside from the previous anti-TNF exposure, eosinophil density in the colon of patients with UC is a negative predictor for a steroid-free long-term response to vedolizumab. The degree colonic eosinophilia may be a novel biomarker that should be further explored.

Plasma Epstein‐Barr virus (EBV) DNA measurement has established prognostic utility in EBV‐driven lymphomas, where it serves as a circulating tumor DNA marker. The value of plasma EBV measurement may be amplified in sub‐Saharan Africa (SSA), where advanced imaging and molecular technologies for risk stratification are not typically available. However, its utility in diffuse large B‐cell lymphoma (DLBCL) is less certain, given that only a subset of DLBCLs are EBV‐positive. To explore this possibility, we measured plasma EBV DNA at diagnosis in a cohort of patients with DLBCL in Malawi. High plasma EBV DNA at diagnosis (≥3.0 log10 copies/mL) was associated with decreased overall survival (OS) (P = .048). When stratified by HIV status, the prognostic utility of baseline plasma EBV DNA level was restricted to HIV‐positive patients. Unexpectedly, most HIV‐positive patients with high plasma EBV DNA at diagnosis had EBV‐negative lymphomas, as confirmed by multiple methods. Even in these HIV‐positive patients with EBV‐negative DLBCL, high plasma EBV DNA remained associated with shorter OS (P = .014). These results suggest that EBV reactivation in nontumor cells is a poor prognostic finding even in HIV‐positive patients with convincingly EBV‐negative DLBCL, extending the potential utility of EBV measurement as a valuable and implementable prognostic marker in SSA., In a cohort of HIV‐positive patients with diffuse large B‐cell lymphoma (DLBCL) in Malawi, we demonstrate that high plasma Epstein‐Barr virus (EBV) DNA level at diagnosis (≥3.0 log10 copies/mL) is associated with decreased overall survival. Notably, even in those HIV‐positive patients with EBV‐negative tumors, high plasma EBV DNA remained associated with shorter survival. These results suggest that EBV reactivation in nontumor cells is a poor prognostic finding in HIV‐positive patients with EBV‐negative DLBCL.

SUMMARY Non-dysphagia symptoms, such as heartburn and dyspepsia, are poorly characterized in adults with eosinophilic esophagitis (EoE). It is unclear if treatment improves these symptoms. The aim of this paper was to assess (i) heartburn and dyspepsia symptom severity in adult EoE patients using validated symptom measures; (ii) change in symptoms after treatment; and (iii) symptom association with endoscopic and histologic features. In a prospective cohort of adult EoE patients who were not responsive to proton pump inhibitor therapy, non-dysphagia symptoms were assessed with heartburn items from the validated GERD-HRQL (gastroesophageal reflux disease health-related quality of life) and SODA (severity of dyspepsia assessment) instruments. Subjects completed the questionnaires at baseline and after treatment. Association of baseline symptoms with endoscopic and histologic features, and before and after treatment with diet or topical steroids, was assessed. Eighty-six EoE patients (mean age 39 years, 57% male, 95% white) completed a baseline questionnaire and 62 completed the follow-up questionnaire. The mean baseline GERD-HRQL score was 4.5 ± 6.5 and the mean total SODA score was 41.0 ± 12.6. At baseline, there was a weak but significant correlation between peak eosinophils and the SODA score (r = 0.28; p = 0.03) and no association between heartburn and SODA scores and endoscopic or other histologic findings. After treatment, there was a decrease in GERD-HRQL heartburn (4.3 vs. 2.6; p = 0.04) and SODA (49.5 vs. 35.5; p = 0.04) scores in histologic responders, but not in nonresponders. In a prospective cohort of EoE patients, baseline eosinophils positively correlated with dyspepsia severity. Heartburn and dyspepsia symptoms improved after treatment in histologic responders.

BACKGROUND AND AIMS: Few factors have been identified that can be used to predict response of patients with eosinophilic esophagitis (EoE) to topical steroid treatment. We aimed to determine whether baseline clinical, endoscopic, histologic, and molecular features of EoE can be used to predict histologic response. METHODS: We collected data from 97 patients with EoE, from 2009 through 2015, treated with a topical steroid for 8 weeks; 59 patients had a histologic response to treatment. Baseline clinicopathologic features and gene expression patterns were compared between patients with a histologic response to treatment (

Book of abstracts from the 2015 conference hosted by the University of Essex.