Relationship Between Non-Hodgkin's Lymphoma and Blood Levels of Epstein-Barr Virus in Children in North-Western Tanzania: A Case Control Study.

Non-Hodgkin's Lymphomas (NHL) are common in African children, with endemic Burkitt's lymphoma (BL) being the most common subtype. While the role of Epstein-Barr Virus (EBV) in endemic BL is known, no data are available about clinical presentations of NHL subtypes and their relationship to Human Immunodeficiency Virus (HIV) infection and Epstein Barr Virus (EBV) load in peripheral blood of children in north-western, Tanzania. A matched case control study of NHL subtypes was performed in children under 15 years of age and their respective controls admitted to Bugando Medical Centre, Sengerema and Shirati district designated hospitals in north-western, Tanzania, between September 2010 and April 2011. Peripheral blood samples were collected on Whatman 903 filter papers and EBV DNA levels were estimated by multiplex real-time PCR. Clinical and laboratory data were collected using a structured data collection tool and analysed using chi-square, Fisher and Wilcoxon rank sum tests where appropriate. The association between NHL and detection of EBV in peripheral blood was assessed using conditional logistic regression model and presented as odds ratios (OR) and 95% confidence intervals (CI). A total of 35 NHL cases and 70 controls matched for age and sex were enrolled. Of NHLs, 32 had BL with equal distribution between jaw and abdominal tumour, 2 had large B cell lymphoma (DLBCL) and 1 had NHL-not otherwise specified (NHL-NOS). Central nervous system (CNS) presentation occurred only in 1 BL patient; 19 NHLs had stage I and II of disease. Only 1 NHL was found to be HIV-seropositive. Twenty-one of 35 (60%) NHL and 21 of 70 (30%) controls had detectable EBV in peripheral blood (OR = 4.77, 95% CI 1.71 - 13.33, p = 0.003). In addition, levels of EBV in blood were significantly higher in NHL cases than in controls (p = 0.024). BL is the most common childhood NHL subtype in north-western Tanzania. NHLs are not associated with HIV infection, but are strongly associated with EBV load in peripheral blood. The findings suggest that high levels of EBV in blood might have diagnostic and prognostic relevance in African children

Elevated numbers of PD-L1 expressing B cells are associated with the development of AIDS-NHL.

The risk for non-Hodgkin lymphoma (NHL) is markedly increased in persons living with human immunodeficiency virus (HIV) infection, and remains elevated in those on anti-retroviral therapy (cART). Both the loss of immunoregulation of Epstein-Barr virus (EBV) infected cells, as well as chronic B-cell activation, are believed to contribute to the genesis of AIDS-related NHL (AIDS-NHL). However, the mechanisms that lead to AIDS-NHL have not been completely defined. A subset of B cells that is characterized by the secretion of IL10, as well as the expression of the programmed cell death ligand-1 (PD-L1/CD274), was recently described. These PD-L1+ B cells can exert regulatory function, including the dampening of T-cell activation, by interacting with the program cell death protein (PD1) on target cells. The role of PD-L1+ B cells in the development of AIDS-NHL has not been explored. We assessed B cell PD-L1 expression on B cells preceding AIDS-NHL diagnosis in a nested case-control study of HIV+ subjects who went on to develop AIDS-NHL, as well as HIV+ subjects who did not, using multi-color flow cytometry. Archival frozen viable PBMC were obtained from the UCLA Multicenter AIDS Cohort Study (MACS). It was seen that the number of CD19+CD24++CD38++and CD19+PD-L1+cells was significantly elevated in cases 1-4 years prior to AIDS-NHL diagnosis, compared to controls, raising the possibility that these cells may play a role in the etiology of AIDS-NHL. Interestingly, most PD-L1+ expression on CD19+ cells was seen on CD19+CD24++CD38++ cells. In addition, we showed that HIV can directly induce PD-L1 expression on B cells through interaction of virion-associated CD40L with CD40 on B cells

IN DIVISION I HOCKEY, DOES THE PUCK STOP JUNIOR YEAR?

The 2004-2005 National Hockey League (NHL) lockout has had a twofold effect on men’s Division I college hockey programs. First, NHL entry-level contracts are now much less expensive than they were before the lockout. As a consequence, NHL teams are now more inclined to induce Division I hockey players to forego years of remaining eligibility. Second, the age of unrestricted free agency has dropped, encouraging rookies to begin their NHL career at a younger age. The authors show that there has been not only a surge in the number of Division I college players who have signed NHL contracts in the two years after 2004-2005 lockout than in the two years before the lockout, but since the lockout disproportionately more NHL bound college players have left college in their junior year.

A mathematical model of Doxorubicin treatment efficacy on non-Hodgkin’s lymphoma: Investigation of current protocol through theoretical modelling results

Doxorubicin treatment outcomes for non-Hodgkin’s lymphomas (NHL) are mathematically modelled and computationally analyzed. The NHL model includes a tumor structure incorporating mature and immature vessels, vascular structural adaptation and NHL cell-cycle kinetics in addition to Doxorubicin pharmacokinetics (PK) and pharmacodynamics (PD). Simulations provide qualitative estimations of the effect of Doxorubicin on high-grade (HG), intermediate-grade (IG) and low-grade (LG) NHL. Simulation results imply that if the interval between successive drug applications is prolonged beyond a certain point, treatment will be inefficient due to effects caused by heterogeneous blood flow in the system

Diabetes and Risk of Non-Hodgkin's Lymphoma

OBJECTIVE: To examine the epidemiologic association between diabetes and risk of non-Hodgkin's lymphoma (NHL). RESEARCH DESIGN AND METHODS: We searched MEDLINE for observational studies on the association between diabetes and NHL in adults using the keywords "diabetes" and "lymphoma." Prospective cohort studies that reported relative risks or standardized incidence ratios and case-control studies that reported odds ratios with 95% CIs were included. A random-effects model was used to combine results from the individual studies. RESULTS: A total of 15 manuscripts (reporting data from 5 prospective cohort and 11 case-control studies) met the inclusion criteria. Combining data from all studies, the risk ratio (RR) of developing NHL in patients with diabetes was 1.19 (95% CI 1.04–1.35). Based on prospective studies, patients with diabetes had an RR of developing NHL of 1.41 (1.07–1.88), without heterogeneity among studies (I2 = 34.3%; P > 0.10). Based on case-control studies, patients with diabetes had an RR of 1.12 (95% CI 0.95–1.31) of developing NHL compared with people without diabetes, with some heterogeneity among studies (I2 = 36.28%; P = 0.09). CONCLUSIONS: Diabetes is associated with a moderately increased risk of NHL, which is consistent with other reported associations between diabetes and malignancies. Future studies should focus on elucidating potential pathophysiologic links between diabetes and NHL.National Institutes of Health grants (R01-DK76092, R0179003, and R2178867

Nanomedicine for the Treatment of Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma, or NHL, is the predominant category of lymphoma. NHL is a type of lymphoid hematopoietic malignancy which approximately 70,000 Americans are diagnosed with annually, with the number of diagnoses growing annually. For decades, chemotherapy was the standard treatment of care, but since the discovery in 1997, monoclonal antibodies are increasingly used as an alternate form of therapy. Nonetheless, almost 20,000 Americans succumb to NHL annually, which highlights the translational gap between preclinical research and the market. Although a lot of progress has been made in therapy options by immunotherapy and combination chemotherapy, the ingenuity of nanomedicine may bridge the translational difficulties while serving as a novel form of therapy capable of eradicating solid tumors. The versatility of nanoparticles allows for personalized approach to NHL, as opposed to generalized medicine, since the subtypes of lymphoma are pathologically very different from one another

Non-Hodgkin’s Lymphoma of the Uterine Cervix

Non Hodgkin’s Lymphoma (NHL) causes many deaths worldwide and its incidence is increasing. They occur commonly in middle aged and elderly people and are disseminated at diagnosis. We present an interesting case of NHL in a 52 years old female, who presented with past a history of postmenopausal bleeding. A 3 x 5 cms endocervical polyp was noticed in the cervix. Biopsy of the polyp revealed it to be a CD20-positive diffuse large B-cell (DLBCL)-type NHL. She was diagnosed as stage IE after staging work-up. She attained a complete response, and has been in remission for 1 year 8 months

Primary Non-Hodgkin's Malignant Lymphoma of the Sinonasal Tract

Primary non-Hodgkin’s lymphomas (NHL) of the sinonasal tract are rather uncommon entities. Morphologically and radiographically, sinonasal lymphomas are difficult to distinguish from other malignant neoplasms or non- neoplastic processes. They have a variable presentation from fulminant destructive manifestations to chronic indolent type of disease and may mimic as carcinomas and invasive fungal infection respectively. We report a case of primary NHL involving sinonasal tract in elderly female, which was clinically and radiologically mimicking as sinonasal malignany and was proven as NHL on histological examination and confirmed by immunohistochemistry. A high index of suspicion, appropriate histopathological examination and immunohistochemistry is necessary to differentiate sinonasal lymphomas from other possibilities. Failure to do so may miss the diagnosis and delay appropriate treatmen