Epidemiologic studies show an association between hepatitis C virus (HCV) and B-cell non-Hodgkin's lymphoma (NHL). Treatment and outcome of patients with diffuse large-cell lymphoma (DLCL) and HCV ...infection are still a matter of debate.
We studied the HCV-positive patients with B-cell DLCL included in the Groupe d'Etude des Lymphomes de l'Adulte (GELA) programs LNH 93 and LNH 98. They were compared with the other patients with DLCL included in these programs. HCV infection prevalence was 0.5% (26 of 5,586 patients).
Histologic types of HCV-positive DLCL were more frequently transformed from low-grade lymphoma than DLCL in HCV-negative patients (32% v 6%, P = .02). This is also supported by more frequent spleen involvement in HCV-positive patients (46% v 17%, P < .001). HCV-positive patients had more frequently elevated lactate dehydrogenase levels than other patients (77% v 55%, P = .02). Outcome of HCV-positive patients was poorer for overall survival (P = .02) but not for event-free survival (P = .13). After matching on age and prognosis factors, at 2 years of follow-up, the overall survival was 56% (95% CI, 33% to 76%) among HCV-positive patients, versus 80% (70% to 89%), and the event-free survival was 53% (33% to 72%) versus 74% (64% to 84%). The short-term hepatic toxicity of chemotherapy was strongly increased among HCV-positive patients. After exclusion of the two subjects with chronic hepatitis B virus infection, the overall proportion of subjects undergoing hepatic toxicity was 65% (15 of 23 patients).
HCV-positive patients with DLCL differ from other patients both at presentation and during chemotherapy. Specific protocols evaluating antiviral therapy should be designed for these patients.
HIV infection is associated with a high incidence of AIDS-related lymphomas (ARLs). Since the use of highly active antiretroviral therapy (HAART), the incidence of AIDS-defining illnesses has ...decreased, leading to a significant improvement in survival of HIV-infected patients. The consequences of HAART use on ARL are under debate. This study compared the incidence and the characteristics of ARL before and after the use of HAART in a large population of HIV-infected patients in the French Hospital Database on HIV (FHDH) and particularly in 3 centers including 145 patients with proven lymphoma. Within the FHDH, the incidence of systemic ARL has decreased between 1993-1994 and 1997-1998, from 86.0 per 10 000 to 42.9 per 10 000 person-years (P < 10−30). The incidence of primary brain lymphoma has also fallen dramatically between the periods, from 27.8 per 10 000 to 9.7 per 10 000 person-years (P < 10−11). The analysis of 145 cases of ARL in 3 hospitals showed that known HIV history was longer in the second period than in the first period among patients with systemic ARL (98 versus 75 months; P < .01). Patients had a higher number of CD4 cells at diagnosis during the second period (191 versus 63/μL, P = 10−3). Survival of patients with systemic ARL also increased between the periods (from 6 to 20 months; P = .004). Therefore, the profile of ARL has changed since the era of HAART, with a lower incidence of systemic and brain ARL. The prognosis of systemic ARL has improved.
Post-transplant non-Hodgkin lymphoma (NHL) is a well-recognized complication of solid-organ transplantation, and pharmacologic suppression of adaptive immunity plays a major role in its development. ...However, the role of natural killer (NK) cells in post-lung transplant de novo NHL is unknown.
Extensive phenotypic analyses of NK cells from patients diagnosed with NHL after liver or lung transplantation were conducted with multicolor flow cytometry. Polyfunctionality assays simultaneously assessed NK cell degranulation (CD107a) and intracellular cytokine production (interferon-γ and tumor necrosis factor-α) in the presence of NHL target cells.
The development of de novo NHL is linked to NK-cell maturation defects, including overexpression of NKG2A and CD62L and down-modulation of inhibitory killer immunoglobulin-like receptors and CD57 receptors. More importantly, in patients who developed NHL after lung transplantation, we observed a specific down-modulation of the activating receptors (NKp30, NKp46, and NKG2D) and a sharp decrease in perforin expression and degranulation against NHL target cells.
Our results suggest that accumulation of abnormal NK cells could play a role in the outgrowth of NHL after lung transplantation, independently of the immunosuppressive regimen.
Abstract : Background: The prevalence of Hepatitis C virus in Egypt reaches 15%, which is considered the highest in the world. Genotype 4 represents 93 % of Egyptian HCV infections. Non-Hodgkin ...lymphoma (NHL) is the 5th most common cancer in Egypt. The association between HCV infection and occurrence of B-cell NHL is well known while data are scarce in Eastern countries. Objectives: We aimed to evaluate the prevalence of HCV infection among patients with B-cell NHL and the clinical characteristics of HCV associated B-cell NHL in Delta region (Mansoura-Egypt). Methods: Between March 2012 and March 2013, 110 adult patients newly diagnosed with B-cell NHL were enrolled in the current study. This study was carried out at Oncology Center, Mansoura University. Study subjects provided serum for HCV testing and for HCV RNA. Results: The prevalence of HCV infection among these patients was 61% (67/110 patients) which is the highest reported value in literature. Among them, 80% (32/40 tested patients) presented with viremia. Contrasting with the histological distribution previously described in Northern regions, the majority of HCV associated lymphomas were DLBCLs (72 %) followed by SLL/CLL (13 %), follicular lymphomas (7.5%) and 7.5% of marginal zone lymphomas. In conclusion: B-cell lymphomas are highly associated with HCV infection in Egypt. Further developments are needed to give access to antiviral treatment for those patients in Delta region.
Epstein-Barr virus (EBV) is the major environmental factor associated with Hodgkin's lymphoma (HL), a common lymphoma in young adults. Natural killer (NK) cells are key actors of the innate immune ...response against viruses. The regulation of NK cell function involves activating and inhibitory Killer cell Immunoglobulin-like receptors (KIRs), which are expressed in variable numbers on NK cells. Various viral and virus-related malignant disorders have been associated with the presence/absence of certain KIR genes in case/control studies. We investigated the role of the KIR cluster in HL in a family-based association study.
We included 90 families with 90 HL index cases (age 16-35 years) and 255 first-degree relatives (parents and siblings). We developed a procedure for reconstructing full genotypic information (number of gene copies) at each KIR locus from the standard KIR gene content. Out of the 90 collected families, 84 were informative and suitable for further analysis. An association study was then carried out with specific family-based analysis methods on these 84 families.
Five KIR genes in strong linkage disequilibrium were found significantly associated with HL. Refined haplotype analysis showed that the association was supported by a dominant protective effect of KIR3DS1 and/or KIR2DS1, both of which are activating receptors. The odds ratios for developing HL in subjects with at least one copy of KIR3DS1 or KIR2DS1 with respect to subjects with neither of these genes were 0.4495% confidence interval 0.23-0.85 and 0.420.21-0.85, respectively. No significant association was found in a tentative replication case/control study of 68 HL cases (age 18-71 years). In the familial study, the protective effect of KIR3DS1/KIR2DS1 tended to be stronger in HL patients with detectable EBV in blood or tumour cells.
This work defines a template for family-based association studies based on full genotypic information for the KIR cluster, and provides the first evidence that activating KIRs can have a protective role in HL.
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