Prolonged Covid‐19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in‐hospital stay (LOS) due to Covid‐19 among patients with lymphoma ...and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid‐19 to 16 French hospitals in March and April, 2020 were included. Length of in‐hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19–92). Ninety‐four patients (85%) had B‐cell non‐Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid‐19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti‐CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1–235). After a median follow‐up of 191 days (3–260), the 6‐month overall survival was 69%. In multivariable analyses, recent administration of anti‐CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42–3.6, p < 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04–4.52, p = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti‐CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid‐19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population.
Summary
It is suspected that primary central nervous system lymphoma (PCNSL) rates are increasing among immunocompetent people. We estimated PCNSL trends in incidence and survival among ...immunocompetent persons by excluding cases among human immunodeficiency virus (HIV)‐infected persons and transplant recipients. PCNSL data were derived from 10 Surveillance, Epidemiology and End Results (SEER) cancer registries (1992–2011). HIV‐infected cases had reported HIV infection or death due to HIV. Transplant recipient cases were estimated from the Transplant Cancer Match Study. We estimated PCNSL trends overall and among immunocompetent individuals, and survival by HIV status. A total of 4158 PCNSLs were diagnosed (36% HIV‐infected; 0·9% transplant recipients). HIV prevalence in PCNSL cases declined from 64·1% (1992–1996) to 12·7% (2007–2011), while the prevalence of transplant recipients remained low. General population PCNSL rates were strongly influenced by immunosuppressed cases, particularly in 20–39 year‐old men. Among immunocompetent people, PCNSL rates in men and women aged 65+ years increased significantly (1·7% and 1·6%/year), but remained stable in other age groups. Five‐year survival was poor, particularly among HIV‐infected cases (9·0%). Among HIV‐uninfected cases, 5‐year survival increased from 19·1% (1992–1994) to 30·1% (2004–2006). In summary, PCNSL rates have increased among immunocompetent elderly adults, but not in younger individuals. Survival remains poor for both HIV‐infected and HIV‐uninfected PCNSL patients.
Polychlorinated biphenyls (PCB) are persistent and bioaccumulative lipophilic substances, mostly used in the past by industry. Known to be cancerogenic, PCB are suspected to increase Non-Hodgkin's ...Lymphoma (NHL) risk in the general population mainly due to evidence from cases-controls studies. Since their interdiction in 1987, diet represents the main route of exposure for the general population, nevertheless no study has assessed the relationship between PCB dietary exposure and NHL risk. The aim of this study was to analyze the association between dietary exposures to dioxin like PCB (DL PCB) and non-dioxin like PCB (NDL PCB) and NHL risk in the E3N prospective cohort of French women.
Among 67,879 women included in this study, 457 cases of NHL were confirmed during 21 years of follow-up. Dietary exposure to PCB was estimated combining food consumption data collected in E3N and food contamination data provided by French Agency for Food, Environmental and Occupational Health & Safety (ANSES) in the second French total diet study. Cox regression models, adjusted for potential confounders, were used to estimate hazard ratio (HR) and 95% confidence intervals (CI).
Average age at diagnosis was 67 years. The median dietary exposure to DL PCB and NDL PCB was, 18.5 pg TEQ/d and 138,843.2 pg/d, respectively. While no association was found between dietary exposure to DL PCB or NDL PCB and overall NHL risk, analyses by NHL histological subgroups showed a positive association between dietary exposures to DL PCB and Diffuse Large B Cell Lymphoma (OR3vs1 1.90, 95%CI 1.03–3.51, ptrend 0.02). Nevertheless these findings were no longer statistically significant when the models were adjusted for fish and dairy products consumption. In addition, an inverse association was found between dietary exposure to NDL PCB and the risk of follicular lymphoma (OR3vs1 0.46, 95%CI 0.24–0.87, ptrend 0.01).
This is the first study to evaluate the association between dietary exposure to DL and NDL PCB and the risk of NHL in a prospective cohort study. Overall, the findings suggest a lack of association between dietary exposure to DL or NDL PCB and NHL risk. Additional studies are needed to reproduce these findings.
•First general population based prospective cohort study investigating the association between PCB and non-Hodgkin’s lymphoma.•Dietary exposure to PCB in French women is not associated with increased risk of non-Hodgkin’s lymphoma overall.•Results suggest a positive association between dietary exposures to dioxin like PCB and diffuse large B cell lymphoma risk.•Results also suggest an inverse association between dietary exposure to non-dioxin like PCB and follicular lymphoma risk.
Epstein-Barr virus (EBV) infection in humans is a major trigger of malignant and nonmalignant B cell proliferations. CD27 is a co-stimulatory molecule of T cells, and inherited CD27 deficiency is ...characterized by high susceptibility to EBV infection, though the underlying pathological mechanisms have not yet been identified. In this study, we report a patient suffering from recurrent EBV-induced B cell proliferations including Hodgkin's lymphoma because of a deficiency in CD70, the ligand of CD27. We show that EBV-specific T lymphocytes did not expand properly when stimulated with CD70-deficient EBV-infected B cells, whereas expression of CD70 in B cells restored expansion, indicating that CD70 on B cells but not on T cells is required for efficient proliferation of T cells. CD70 was found to be up-regulated on B cells when activated and during EBV infection. The proliferation of T cells triggered by CD70-expressing B cells was dependent on CD27 and CD3 on T cells. Importantly, CD27-deficient T cells failed to proliferate when stimulated with CD70-expressing B cells. Thus, the CD70-CD27 pathway appears to be a crucial component of EBV-specific T cell immunity and more generally for the immune surveillance of B cells and may be a target for immunotherapy of B cell malignancies.
Background
International guidelines suggest hepatitis C virus (HCV) eradication by direct‐acting antivirals (DAAs) after first‐line immunochemotherapy (I‐CT) in patients with HCV‐positive diffuse ...large B‐cell lymphoma (DLBCL), although limited experiences substantiate this recommendation. Moreover, only a few data concerning concurrent administration of DAAs with I‐CT have been reported.
Subjects, Materials, and Methods
We analyzed hematological and virological outcome and survival of 47 consecutive patients with HCV‐positive DLBCL treated at 23 Italian and French centers with DAAs either concurrently (concurrent cohort ConC: n = 9) or subsequently (sequential cohort SeqC: n = 38) to first‐line I‐CT (mainly rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone R‐CHOP‐like).
Results
Median age was 61 years, 89% of patients had stage III/IV, and 25% presented evidence of cirrhosis. Genotype was 1 in 56% and 2 in 34% of cases. Overall, 46 of 47 patients obtained complete response to I‐CT. All patients received appropriate DAAs according to genotype, mainly sofosbuvir‐based regimens (n = 45). Overall, 45 patients (96%) achieved sustained virological response, 8 of 9 in ConC and 37 of 38 in SeqC. DAAs were well tolerated, with only 11 patients experiencing grade 1–2 adverse events. Twenty‐three patients experienced hepatic toxicity (grade 3–4 in seven) following I‐CT in SeqC, compared to only one patient in ConC. At a median follow‐up of 2.8 years, two patients died (2‐year overall survival, 97.4%) and three progressed (2‐year progression‐free survival, 93.1%).
Conclusion
Excellent outcome of this cohort of HCV‐positive DLBCL suggests benefit of HCV eradication by DAAs either after or during I‐CT. Moreover, concurrent DAAs and R‐CHOP administration appeared feasible, effective, and ideally preferable to deferred administration of DAAs for the prevention of hepatic toxicity.
Implications for Practice
Hepatitis C virus (HCV)‐associated diffuse large B‐cell lymphomas (DLBCLs) represent a great therapeutic challenge, especially in terms of hepatic toxicity during immune‐chemotherapy (I‐CT) and long‐term hepatic complications. The advent of highly effective and toxicity‐free direct‐acting antivirals (DAAs) created an exciting opportunity to easily eradicate HCV shortly after or in concomitance with first‐line immunochemotherapy (usually R‐CHOP). This retrospective international study reports the real‐life use of the combination of these two therapeutic modalities either in the concurrent or sequential approach (DAAs after I‐CT) in 47 patients. The favorable reported results on long‐term outcome seem to support the eradication of HCV with DAAs in all patients with HCV‐positive DLBCL. Moreover, the results from the concurrent approach were effective and safe and displayed an advantage in preventing hepatic toxicity during I‐CT.
Epidemiological studies have established that hepatitis C virus (HCV) is associated with diffuse large B‐cell lymphoma (DLBCL). This article reports on patients with HCV‐positive DLBCL treated with direct‐acting antivirals either concurrently or subsequently to a curative‐intent first‐line immunochemotherapy.
Non-Hodgkin lymphoma (NHL) comprises distinct tumor subtypes. Although mortality from NHL overall has changed dramatically in the United States over time, little is known about trends for subtypes, ...because death certificates do not record this information.
Using data from U.S. Surveillance, Epidemiology, and End Results (SEER) areas, we assessed NHL mortality rates and mapped NHL deaths to incident NHL cases in SEER cancer registries. This allowed us to evaluate population-level mortality trends attributed to specific NHL subtypes (incidence-based mortality; IBM). We also describe NHL incidence and survival after NHL diagnosis by calendar year. We used Joinpoint to identify years when IBM and incidence rate trends changed slope.
Overall NHL mortality rates increased during 1975-1997, peaking at 10.9 per 100,000 person-years, then decreased subsequently in 1997-2011. Overall IBM rates mirror this trend during 1990-2011. For B-cell NHL subtypes, IBM rates decreased beginning in the mid-1990s, with yearly declines of -3.0% for diffuse large B-cell lymphoma (DLBCL), -2.7% for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and -5.3% for follicular lymphoma. Incidence rates for these subtypes did not decrease until after 2003. Corresponding 5-year cancer-specific survival increased dramatically over time for DLBCL (from 37%-66%), CLL/SLL (69%-84%), and follicular lymphoma (69%-82%). IBM for peripheral T-cell lymphoma was flat during 2006-2011, although incidence increased.
Mortality due to three common B-cell NHL subtypes has fallen over time in the United States.
This decline reflects better survival after NHL diagnosis, likely from improved therapies, because the decline in NHL incidence occurred later.
Classical Hodgkin Lymphoma incidence increases in HIV-1-infected patients (HIV-cHL). HIV infection is associated with higher B-cell activation. Here, in 38 HIV-cHL patients from the French cohort ...ANRS-CO16 Lymphovir, we examined longitudinally over 24 months the serum levels of the B-cell activating cytokines IL10, IL6, and BAFF, and blood distribution of B-cell subsets. Fourteen HIV-cHL patients were also compared to matched HIV-infected controls without cHL. IL10, IL6, and BAFF levels were higher in HIV-cHL patients than in controls (
< 0.0001,
= 0.002, and
< 0.0001, respectively). Cytokine levels increased in patients with advanced-stage lymphoma compared to those with limited-stage (
= 0.002,
= 0.03, and
= 0.01, respectively). Cytokine levels significantly decreased following HIV-cHL diagnosis and treatment. Blood counts of whole B-cells were similar in HIV-cHL patients and controls, but the distribution of B-cell subsets was different with higher ratios of naive B-cells over memory B-cells in HIV-cHL patients. Blood accumulation of naive B-cells was more marked in patients with advanced cHL stages (
= 0.06). During the follow-up, total B-cell counts increased (
< 0.0001), and the proportion of naive B-cells increased further (
= 0.04). Together the results suggest that in HIV-infected patients, cHL is associated with a particular B-cell-related environment that includes increased production of B-cell-activating cytokines and altered peripheral distribution of B-cell subsets. This B-cell-related environment may fuel the process of tumorigenesis.
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