Objectives: The aim of this study is to compare the toxicity profiles of SMILE versus less intense L-asparaginase-containing regimens, CCRT or "sandwich" RT+CT regimens. Methods: PRISMA protocol was used to search Pubmed and Embase for studies of treatment regimens for extranodal NK/T-cell lymphoma, nasal type (ENKTL) in English published before March 2018. Pooled data were grouped into five categories: A) CHOP-like regimens; B) Gemcitabine-based regimens; C) SMILE-like regimens; D) Concurrent and "sandwich" RT + CT; and E) Methotrexate-based combinations. We pooled prevalence of selected adverse events from each study to calculate the weighted overall prevalence using meta-proportion in Stata. Results: Group C was the most toxic with the pooled neutropenia 72% (95 CI 64;80) and thrombocytopenia 48% (95% CI 40;55) prevalence. The use of Group D treatment regimens was associated with the lowest anemia (10% (95% CI 1;19)) prevalence. Group E was the least toxic with regard to thrombocytopenia (6% (95% CI 1;11). Conclusion: Our analysis confirms that SMILE regimen, which is current standard to treat advanced-stage ENKTL may be associated with more severe hematological toxicity compared to other L-asparaginase combinations, including methotrexate-based (AspaMetDex, MESA and MEDA) or gemcitabine-based (GELOX, PGEMOX, DDGP, GDL, GOLD, GLIDE) or CCRT-based regimens.
Keywords: Extra-nodal NK/T cell lymphoma; L-asparaginase-based regimens; systematic review; tolerability; toxicity.