Features of high-dose chemotherapy regimens with the inclusion of 5-azacitidine and autologous hematopoietic stem cell transplantation in the treatment of children older than three years with high-risk medulloblastoma

Dailidite Widmatne Widmanto, Subbotina Natalya Nikolaevna, Mentkevich Georgy Lydomirovich, Dolgopolov Igor Stanislavovich, Levashov Alexey Sergeevich

Background: research in recent decades has significantly improved the effectiveness of the treatment medulloblastoma in children. Thus, the combination of chemotherapy and radiation exposure demonstrates survival rates above 90% in the middle-risk group and above 60% in the high-risk group. The study of possible improvements in existing therapy regimens is aimed at improving treatment outcomes in patients with an unfavorable tumor prognosis. Objective: in our study, we attempted to improve the effectiveness of treatment of high-risk medulloblastoma by modifying the existing regimen of high-dose chemotherapy with demythylating agent-5-azacitidine. Materials and methods: the study was conducted in a group of 7 patients older than 3 years who were treated for high-risk medulloblastoma in the conditions of the research Institute of ONCOLOGY. N. N. Blokhin in the period from November 2016 to December 2017 the Scheme of therapy included two courses of VDHT scheme thiotepa 600 mg/m2/dose, carboplatin 1020 mg/m2/dose with auto-TGX during the consolidation phase, enhanced by the inclusion in the conditioning regimen of 5-azacitidine in a total dose of 375 mg/m2. The control group included 7 patients whose consolidation stage was carried out without modification. Results: in both groups of patients, comparable results of 2-year relapse-free survival (BRV) were achieved: in the study group 84.3%±15.2%, in the control group 85.7%±13.2% (p=0.08), while there was a significant increase in the degree of total organ toxicity when using 5-azacitidine (p=0.04). Conclusions: the use of 5-azacitidine in VDCT regimens with auto-THSC in the treatment of medulloblastoma of adverse prognosis in children older than three years showed no improvement in the effectiveness of treatment. Modes VDHT with vidaza showed a greater toxicity, and increase in periods of aplasia of the bone marrow.

Keywords:results, patients, treatment effectiveness, conditions, terms