Incidence and risk factors for central nervous system relapse in patients with primary mediastinal large B-cell lymphoma in the rituximab era.

Central nervous system (CNS) involvement is rare in primary mediastinal large B-cell lymphoma (PMLBCL). We aimed to evaluate the incidence of CNS relapse as first treatment failure event and the effect of the induction chemotherapy regimen, central nervous system - international prognostic index (CNS-IPI) and other clinical and laboratory variables on the risk of CNS relapse in 564 PMLBCL patients treated with immunochemotherapy. Only 17 patients (3.0%) received CNS prophylaxis. During a 55-month median follow-up only 8 patients experienced CNS relapse as first event, always isolated. The 2-year cumulative incidence of CNS relapse (CI-CNSR) was 1.47% and remained unchanged thereafter. The CI-CNSR was not affected by the chemotherapy regimen (R-CHOP or R-da-EPOCH). None of the established International Prognostic Index factors for aggressive lymphomas predicted CNS relapse in PMLBCL. The 2-year CI-CNSR in patients with versus without kidney involvement was 13.3% versus 0.96% (p < 0.001); 14.3% versus 1.13% with versus without adrenal involvement (p < 0.001); and 10.2% versus 0.97% with versus without either kidney or adrenal involvement. CNS-IPI was also predictive (2-year CI-CNSR in high-risk vs. intermediate/low-risk: 10.37% vs. 0.84%, p < 0.001). However, this association may be driven mainly by kidney and/or adrenal involvement. In conclusion, in PMLBCL, CNS relapse is rare and appears to be strongly associated with kidney and/or adrenal involvement.

Real-life Experience With Rituximab-CHOP Every 21 or 14 Days in Primary Mediastinal Large B-cell Lymphoma.

BACKGROUND/AIM: Primary mediastinal large B-cell lymphoma (PMLBCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL), whose prognosis has greatly improved since the incorporation of the anti-CD20 monoclonal antibody rituximab into current therapeutic regimens. Evidence, however, on the optimal time interval between consecutive chemoimmunotherapy (CIT) cycles is still scarce. This study aimed to evaluate the efficacy outcomes of the more commonly administered 3-weekly regimens to the biweekly ones in a PMLBCL patients' population, who were mostly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 21 days (R-CHOP-21) or R-CHOP-14. PATIENTS AND METHODS: We retrospectively studied our cohort of consecutively treated PMLBCL patients, focusing on their treatment density, in order to determine possible differences in treatment outcomes. RESULTS: CIT, in the form of both R-CHOP-21 as well as R-CHOP-14 (or similar regimens), is highly active in PMLBCL, with low rates of early treatment failure. In our cohort of patients, R-CHOP-14 did not result in a meaningful improvement of freedom from progression (FFP) or overall survival (OS). CONCLUSION: Both R-CHOP-14 and R-CHOP-21 are probably equally effective in PMLBCL, yet further, prospective, randomized studies are warranted to clarify whether dose-dense regimens can be associated with better disease control and long-term results.

Tobacco smoking and risk of multiple myeloma: a meta-analysis of 40 observational studies.

This meta-analysis aims to quantitatively synthesize all available data on the association between tobacco smoking and multiple myeloma (MM) risk. Eligible studies were identified and pooled effect estimates (odds ratios and relative risks) were calculated regarding ever, current and former smoking. Separate analyses were performed on case-control and cohort studies, as well as on males and females. Meta-regression analysis with percentage of males, mean age, years of smoking, pack-years, cigarettes per day, years since quit and age at onset was performed. Forty articles were deemed eligible; of them 27 used a case-control design (4,625 cases and 21,591 controls) and 13 used a cohort design (2,228 incident cases among a total cohort size equal to 1,852,763 subjects). Ever smoking was not associated with MM risk (pooled effect estimate = 0.92, 95% confidence interval (CI): 0.85-1.00); similar results were obtained for current (pooled effect estimate = 0.87, 95% CI: 0.74-1.03) and former smoking (pooled effect estimate = 1.04, 95% CI: 0.96-1.13). Regarding ever smoking, the null association was reproducible upon cohort studies (pooled effect estimate = 1.01, 95%CI: 0.89-1.15), whereas the inverse association in case-control studies (pooled effect estimate = 0.87, 95% CI: 0.78-0.96) was particularly due to the bias-prone hospital-based ones. Meta-regression analysis did not yield statistically significant results. In conclusion, MM does not seem to be associated with tobacco smoking. There is a need to further explore how molecular mechanisms are involved in the resistance of MM progenitor cells toward smoking.