GONADOTOXICITY OF RISK-ADAPTED THERAPY OF HODGKIN'S LYMPHOMA CONDUCTED IN CHILDHOOD AND ADOLESCENT AGE

Objective: assessment of the gonadotoxicity of modern treatment regimens for Hodgkin’s lymphoma (HL) in children and adolescents; identification of treatment factors associated with impairment of sexual glands. Methods. All patients participating in the study received risk-adapted treatment programs: DAL-HD (German working group for the study of Hodgkin’s lymphoma in children) and the original SPbHL protocol developed by the St. Petersburg group of scientists. The number of cycles of polychemotherapy and the regimen of radiation therapy depended on the risk group to which the child belonged. Since 2010, in children, stratified in the group of unfavorable prognosis, the treatment program consisted of 6 courses of BEACOPP-basic («early intensification» program). Results. Data of 52 patients with HL treated in the department of chemotherapy and combined treatment of malignant tumors in children of the N.N. Petrov NMRC of Oncology from 1993 to 2015 were analyzed. The mean age of patients who underwent assessment of fertility was 24±0.9 years. The greatest gonadotoxic effect was possessed by the DAL-HD program and the chemotherapy regimen (BEACOPP-basic), the smaller - by the SPbHL program. Inhibition of fertile function was detected in 42.9% of patients in the DAL-HD group and in 13.2% of patients in the BEACOPP-basic group; there was no hypofunction of the sexual glands in patients in the SPbHL group. Statistical analysis revealed that the development of fertility dysfunction was significantly affected by irradiation of the lymph nodes located below the diaphragm (p=0.00685), the use of DAL-HD programs and «early intensification» programs (p=0.0000), age at the time of treatment younger than 12 years (p=0.00017), a cumulative dose of cyclophosphamide exceeding 3900 mg/m2 (p=0.00001), and procarbazine above 3000 mg/m2 (p=0.00013). Conclusion. DAL-HD and BEACOPP-basic treatment programs for HL are accompanied by development of fertile dysfunction, in contrast to the SPbLH program, in which such violations were not observed during the study period. The main therapeutic factors that exert a gonadotoxic effect include the use of alkylating agents as well as radiotherapy for lymph collectors located below the diaphragm.

Hodgkin's lymphoma, gonadotoxicity, alkylating drugs, radiation therapy