Reproductive adverse events in patients with non-Hodgkin lymphoma treated with chemotherapeutic regimens including cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or CHOP with rituximab (R-CHOP): A systematic review and meta-analysis

Abstract Introduction: The therapeutic regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP with rituximab (R-CHOP) is the first-line treatment regimen for non-Hodgkin lymphoma (NHL). NHL patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP with rituximab (R-CHOP) have a high risk of reproductive adverse events. The aim of this systematic review and meta-analysis was to evaluate the reproductive toxicity of this regimen and make further reasonable suggestions on reproductive protection. Methods: We systematically searched with appropriate terms from January 1980 to June 2021 for observational studies in adult patients who had the risk of reproductive toxicity associated with the CHOP/R-CHOP regimen, without any language or publication-type restriction. We conducted meta-analyses of one-sample proportions of patients suffering reproductive adverse events after using CHOP/R-CHOP. In addition, subgroup analyses were performed to determine the effect of sex. Result: A total of 9 articles involving 331 patients were included in the meta-analysis, and the pooled proportion of reproductive adverse events was computed to be 22.3% (95% confidence interval [CI] 11.4%–33.2%; heterogeneity test Q=65.3; τ²=0.0231; I²=87.70%; p<0.001) using the random-effects model. A total of 205 male patients were included in this meta-analysis, which used a random-effects model. The pooled proportion of male gonadal toxicity was 29.2% (95% CI 11. 0%– 47.4%; heterogeneity test Q=46.65; τ²=3.055; I²=89.3%; p<0.0001). The pooled proportion of female gonadal toxicity was 16.5% (95% CI 8.5%– 24.5%; heterogeneity test Q=18.6; τ²=0.0112; I²=67.8%; p=0.005). Conclusion: The findings suggest that NHL patients have a relatively high risk of reproductive adverse events after treatment with CHOP/R-CHOP. Men are more likely to have gonadal damage than women. Evaluation of reproductive function is particularly necessary both before and after treatment. Some reproductive protection strategies implemented for those patients who want to preserve their fertility.