Background Relatively little information is available on the incidence of secondary cancer in non-Hodgkin’s lymphoma. The aim of this long-term follow-up study was to determine the incidence, the time free of second tumors, and risk factors for developing secondary cancer in a homogeneous group of patients with non-Hodgkin’s lymphoma. Design and Methods We evaluated a total of 563 patients with indolent non-Hodgkin’s lymphoma enrolled in Gruppo Italiano Studio Linfomi trials from 1988 to 2003. Results After a median follow-up of 62 months, 39 patients (6.9%) developed secondary cancer: 12 myelodysplastic syndromes/acute myeloid leukemia, and 27 solid tumors. The overall standardized incidence ratio of secondary malignancy in patients with non-Hodgkin’s lymphoma was higher than the risk of malignancy in the general population. The standardized incidence ratio was elevated in male patients and in patients under 65 years old at first treatment. Overall, the cumulative incidence of secondary cancer at 12 years was 10.5%, after correction in a competing-risk model. Univariate and multivariate Cox regression analyses showed that older age at the time of diagnosis, male sex, and fludarabine-containing therapy had significant negative impacts on the time free of second tumors. Conclusions We have identified subgroups of non-Hodgkin’s lymphoma patients with increased standardized incidence ratios of secondary malignancy and variables that have a negative impact on the time free of second tumors. This information could help physicians to select the most appropriate treatments. Finally, taking into account the possible occurrence of secondary neoplasia, long-term monitoring must be considered.

We assessed the prognostic value of minimal residual disease (MRD) within the ML17638 phase 3 trial from the Fondazione Italiana Linfomi, investigating the role of rituximab maintenance in elderly follicular lymphoma (FL) patients after a brief first-line chemoimmunotherapy. MRD for the bcl-2/IgH translocation was determined on bone marrow cells in a centralized laboratory belonging to the Euro-MRD consortium, using qualitative and quantitative polymerase chain reactions (PCRs). Of 234 enrolled patients, 227 (97%) were screened at diagnosis. A molecular marker (MM) was found in 51%. Patients with an MM were monitored at 8 subsequent times. Of the 675 expected follow-up samples, 83% were analyzed. Conversion to PCR negativity predicted better progression-free survival (PFS) at all post-treatment times (eg, end of therapy: 3-year PFS, 72% vs 39%; P < .007). MRD was predictive in both maintenance (83% vs 60%; P < .007) and observation (71% vs 50%; P < .001) groups. PCR positivity at the end of induction was an independent adverse predictor (hazard ratio, 3.1; 95% confidence interval, 1.36-7.07). MRD is a powerful independent outcome predictor in FL patients who receive rituximab-intensive programs, suggesting a need to investigate its value for decision-making. This trial was registered at www.clinicaltrial.gov as #NCT01144364. Key Points PCR negativity is a strong outcome predictor after rituximab-intensive immunochemotherapy at multiple posttreatment times. PCR is predictive even when maintenance is delivered, and accumulation of PCR-negative results further reduces the likelihood of relapse.

In this study we assessed the prognostic significance of absolute monocyte count and selected the best cut-off value at diagnosis in a large cohort of patients with diffuse large B-cell lymphoma. Data were retrieved for therapy-naïve patients with diffuse large B-cell lymphoma followed in Israel and Italy during 1993–2010. A final cohort of 1017 patients was analyzed with a median follow up of 48 months and a 5-year overall survival rate of 68%. The best absolute monocyte count cut-off level was 630/mm³ and the 5-year overall survival for patients with counts below this cut-off was 71%, whereas it was 59% for those with a count >630 mm³ (P=0.0002). Of the 1017 patients, 521 (51%) were treated with chemo-immunotherapy, and in this cohort, using multivariate analysis, elevated monocyte count retained a negative prognostic value even when adjusted for International Prognostic Index (HR1.54, P=0.009). This large study shows that a simple parameter such as absolute monocyte count (>630/mm³) can easily be used routinely in the evaluation of newly diagnosed diffuse large B-cell lymphoma to identify high-risk patients with a worse survival in the rituximab era.

Background: Late side-effects are becoming an important issue in non-Hodgkin’s lymphoma (NHL) survivors. We intended to estimate pooled relative risk (RR) of secondary malignant neoplasms (SMNs), to evaluate site-associated RR and the impact of different treatments. Design: We carried out an electronic search of Medline and EMBASE seeking articles investigating the risk of SMNs and reporting RR measures. The studies were evaluated for heterogeneity before meta-analysis and for publication bias. Pooled RRs were estimated using fixed- and random-effects models. Results: A total of 23 studies met the inclusion criteria. Pooled RRs of SMNs overall and for solid tumors were 1.88 and 1.32, respectively. We found an excess of risk for several specific cancer sites. Radiotherapy alone did not increase the risk for SMNs, while chemotherapy and combined treatments augmented the RR. Regression analyses revealed a positive significant association for all SMNs with total body irradiation, and for solid SMNs with younger age. No publication bias was observed. Conclusions: Our results indicate that NHL patients experience a higher risk for SMNs than the general population and that various treatments have different impact on RR. More information will be necessary to evaluate possible interactions with genetic susceptibility and environmental exposure.

Background: Improved treatment have modified survival outcome in patients with diffuse large B-cell lymphoma (DLBCL) and altered the importance of previously recognized prognostic markers. Design and methods: To evaluate International Prognostic Index (IPI) score before and after rituximab introduction and to validate the absolute lymphocyte count (ALC)/revised International Prognostic Index (R-IPI) model, we carried out a retrospective analysis on a total of 831 patients with DLBCL. Results: Our results show that IPI lost its discriminating power with the introduction of rituximab. The analysis of our second set allowed us to validate the ALC/R-IPI model. The R-IPI and ALC/R-IPI could still be used for designing clinical trials, but both have difficulty recognizing a high percentage of poor prognosis patients, though it remains an important goal of a good prognostic model considering the modest impact of salvage treatments on survival. Conclusions: A new model on the basis of significant variables in the rituximab era and built on a large database of patients treated with rituximab is urgently needed. As prognostic models are changing with the efficacy and mechanisms of action of treatment utilized, looking for a new prognostic score is a never-ending story in which researchers are trying to hit a continuously moving target.