Oncogenic Mutations of MYD88 and CD79B in Diffuse Large B-Cell Lymphoma and Implications for Clinical Practice

Simple SummaryA diagnosis of diffuse large B-cell lymphoma in our therapeutic era should be implemented by the definition of the cell of origin, additional immunohistochemistry (i.e., BCL2 and MYC), and by fluorescent in-situ hybridization. The next step, suggested by the seminary works we will discuss in this review, will be to implement the definition of sub-categories by the recognition of single gene mutations and pathways that may be targetable by newer drugs. We here describe the impact that MYD88 and CD79B activating mutations, two of the most frequent mutations in several DLBCL subtypes, may achieve in the next future in the diagnosis and therapeutics of such a relevant lymphoma subtype.Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma in adults. Despite the recognition of transcriptional subtypes with distinct functional characteristics, patient outcomes have not been substantially altered since the advent of chemoimmunotherapy (CIT) twenty years ago. Recently, a few pivotal studies added to the disease heterogeneity by describing several activating mutations, which have been associated with disease presentation, B-cell function and behavior, and final outcome. DLBCL arises from antigen exposed B-cells, with the B-cell receptor (BCR) playing a central role. BCR-activity related mutations, such as CD79B and MYD88, are responsible for chronic activation of the BCR in a substantial subset of patients. These mutations, often coexisting in the same patient, have been found in a substantial subset of patients with immune-privileged (IP) sites DLBCLs, and are drivers of lymphoma development conferring tissue-specific homing properties. Both mutations have been associated with disease behavior, including tumor response either to CIT or to BCR-targeted therapy. The recognition of CD79B and MYD88 mutations will contribute to the heterogeneity of the disease, both in recognizing the BCR as a potential therapeutic target and in providing genetic tools for personalized treatment

Life-Threatening Protein-Losing Enteropathy Due To Human Cytomegalovirus Infection Upon Immunochemotherapy

Immunochemotherapy adverse events affecting the gastrointestinal tract usually consist of self-limiting nausea/ vomiting or diarrhoea, while bleeding and perforation are rare. A 42-year-old woman treated with bendamustine/ rituximab for splenic marginal zone lymphoma developed alife-threatening protein-losing enteropathy that was a diagnosis conundrum, ranging from drug-induced, immunemediated, neoplastic and infectious forms. Suspecting opportunistic viral infection but with unremarkable immunohistochemistry and peripheral blood tests, the diagnosis of Human Cytomegalovirus enteritis was made only by means of quantitative real-time polymerase chain reaction carried out on mucosal specimens. Steroid discontinuation and a prolonged course of antiviral therapy allowed the patient to overcome the critical phase and to achieve gradual normalisation of stool frequency, body mass index, laboratory tests lasting one year, while disappearance of mucosal viral load resulted soon evident. Human Cytom-egalovirus end-organ disease localised at the gastrointestinal tract is a serious condition whose prompt diagnosis and treatment prevents poor patients prognosis

Efficacy of R-COMP in comparison to R-CHOP in patients with DLBCL: A systematic review and single-arm metanalysis

Doxorubicin represents the mainstay in the upfront treatment of diffuse large B-cell lymphoma (DLBCL) patients. However, its administration is sometimes hampered by the coexistence of former comorbidities/cardiac issues, especially in the elderly population. Liposome encapsulated drug delivery systems have been adopted to reduce the exposure of normal tissues to the drug, both in solid cancers and lymphomas. Despite claims for lower toxicity, the efficacy of non-pegylated liposome doxorubicin (NPLD) in DLBCL, as compared to standard doxorubicin, has never been established. We systematically reviewed relevant literature of NPLD in lymphoma treatment. Adjusting for age/comorbidities, our metanalysis revealed that the use of combinations including NPLD (R-COMP) were non-inferior in terms of response, overall and progression-free survival to the standard of care (R-CHOP) in overlapping series of DLBCL patients. R-COMP may represent a safe and active option for elderly patients with DLBCL, or for those with some extent of cardiac impairment at baseline

Severe hypoglycemia in patients with known diabetes requiring emergency department care: A report from an Italian multicenter study

Aims: To describe the characteristics and associated risk factors of patients with established diabetes who required Emergency Department (ED) care for severe hypoglycemia. Methods: We performed an observational retrospective study to identify all cases of severe hypoglycemia among attendees at the EDs of three Italian University hospitals from January 2010 to December 2014. Results: Overall, 520 patients with established diabetes were identified. Mean out-of-hospital blood glucose concentrations at the time of the hypoglycemic event were 2.2 ± 1.3 mmol/L. Most of these patients were frail and had multiple comorbidities. They were treated with oral hypoglycemic drugs (43.6%), insulin (42.8%), or both (13.6%). Among the oral hypoglycemic drugs, glibenclamide (54.5%) and repaglinide (25.7%) were the two most frequently used drugs, followed by glimepiride (11.3%) and gliclazide (7.5%). Hospitalization rates and in-hospital deaths occurred in 35.4% and in 2.3% of patients, respectively. Cirrhosis (odds ratio [OR] 6.76, 95% confidence interval [CI] 1.24–36.8, p < 0.05), chronic kidney disease (OR 2.42, 95% CI 1.11–8.69, p < 0.05) and center (Sapienza University OR 3.70, 95% CI 1.57–8.69, p < 0.05) were the strongest predictors of increased rates of hospital admission. Conclusions: Severe hypoglycemia is a remarkable burden for patients with established diabetes and increases the risk of adverse clinical outcomes (in-hospital death and hospitalization), mainly in elderly and frail patients. This study further reinforces the notion that careful attention should be taken by health care providers when they prescribe drug therapy in elderly patients with serious comorbidities