Risk for second malignancies in non-Hodgkin's lymphoma survivors: a meta-analysis

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.