Diffuse large B-cell lymphoma with testicular involvement: outcome and risk of CNS relapse in the rituximab era.

The addition of rituximab has improved outcomes in diffuse large B-cell lymphoma (DLBCL), however, there remains limited information on the impact of rituximab in those with testicular involvement. All patients with diffuse large cell lymphoma and testicular involvement treated with curative intent were identified in the British Columbia Cancer Agency Lymphoid Cancer Database. In total, 134 patients diagnosed between 1982 and 2015 with diffuse large cell lymphoma involving the testis were identified: 61 received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like chemotherapy and 73 received CHOP plus rituximab (R-CHOP). A greater proportion of R-CHOP treated patients had higher International Prognostic Index (IPI, P = 0·005). In multivariate analysis, the protective effect of rituximab on progression-free survival (hazard ratio (HR) 0·42, P < 0·001), overall survival (HR 0·39, P < 0·001) and cumulative incidence of progression (HR 0·46, P = 0·014) were independent of the IPI. However, in a competing risk multivariate analysis including central nervous system (CNS) prophylaxis and the CNS-IPI, rituximab was not associated with a decreased risk of CNS relapse. The addition of rituximab has reduced the risk of lymphoma recurrence in testicular DLBCL, presumably through improved eradication of systemic disease. However, CNS relapse risk remains high and further studies evaluating effective prophylactic strategies are needed.

Two distinct syndromes of lymphoma-associated AL amyloidosis: a case series and review of the literature.

Light chain (AL) amyloidosis has a rare association with non-Hodgkin lymphoma (NHL). Both peritumoral and systemic AL amyloidosis have been reported, but a detailed description of these syndromes is lacking. We describe 10 patients with lymphoma associated AL amyloidosis. NHL patients with peritumoral amyloidosis had low or undetectable levels of monoclonal (M) protein, mostly single organ involvement(lung or soft tissue), and underlying extranodal marginal zone lymphoma, mucosa associated lymphoid tissue subtype. NHL patients with systemic amyloidosis had high levels of M-protein, multiorgan involvement with frequent cardiac involvement, and predominantly underlying lymphoplasmacytic lymphoma. Systemic amyloidosis was associated with inferior outcomes

Salvage chemotherapy and autologous stem cell transplant in primary refractory diffuse large B-cell lymphoma: outcomes and prognostic factors.

Patients with primary refractory diffuse large B-cell lymphoma (REF DLBCL: progression on or within 3 months of completion of primary therapy) sensitive to salvage chemotherapy undergo autologous stem cell transplant (ASCT). We conducted a retrospective review of 111 patients with REF DLBCL treated between 1999 and 2007. Primary treatment consisted of cyclophosphamide, adriamycin, vincristine and prednisone (CHOP; 66%) and rituximab with CHOP (R-CHOP; 33%); 14% received involved field radiation. The response rate (RR) to first salvage chemotherapy was 23% (RR by regimen: dexamethasone, cytosine arabinoside and cisplatin [DHAP] 15%, etoposide, Solu-Medrol, cytosine arabinoside and cisplatin [ESHAP] 36%, and gemcitabine, dexamethasone and cisplatin [GDP] 45%); 25% (n = 28) of patients underwent ASCT. With a median follow-up of 5.9 months (range 1-94), the median progression-free and overall survival from primary treatment failure was 3 and 10 months, respectively. Outcomes in patients with REF DLBCL after CHOP or R-CHOP appear equally poor. Second-generation platinum-containing regimens (ESHAP, GDP) may be superior to DHAP in this setting. Novel, prospectively evaluated treatment approaches should be pursued in REF DLBCL.

Phosphatidylinositol 3-kinases in carcinoembryonic antigen-related cellular adhesion molecule-mediated internalization of Neisseria gonorrhoeae.

Neisseria gonorrhoeae can be internalized by mammalian cells through interactions between bacterial opacity-associated (Opa) adhesins and members of the human carcinoembryonic antigen-related cellular adhesion molecule (CEACAM) family. We examined the role of phosphatidylinositol 3-kinases (PI3Ks) in gonococcal invasion of epithelial cell lines expressing either CEACAM1 or CEACAM3. CEACAM3-mediated internalization, but not that mediated by CEACAM1, was accompanied by localized and transient accumulation of the class I PI3K product phosphatidylinositol 3,4,5-trisphosphate at sites of bacterial engulfment. Inhibition of phosphatidylinositol 3-kinases reduced CEACAM3-mediated uptake but, paradoxically, led to an increase in intracellular survival of bacteria internalized via either CEACAM1 or CEACAM3, suggesting additional roles for PI3K products. Consistent with this finding, the class III PI3K product phosphatidylinositol 3-phosphate accumulated and persisted in the membrane of gonococcal phagosomes after internalization. Inhibition of PI3K blocked phagosomal acquisition of the late endosomal marker lysosome-associated membrane protein 2 and reduced phagosomal acidification. Inhibiting phagosomal acidification with concanamycin A also increased survival of intracellular gonococci. These results suggest two modes of action of phosphatidylinositol 3-kinases during internalization of gonococci: synthesis of phosphatidylinositol 3,4,5-trisphosphate is important for CEACAM3-mediated uptake, while phosphatidylinositol 3-phosphate is needed for phagosomal maturation and acidification, which are required for optimal bacterial killing.