Intensive regimens of chemotherapy with hematopoetic stem cell rescue in paediatric patients with high-risk malignant tumors

Abstract

Background. One of the possible options to intensify therapy in patients with high-risk malignant tumors is high-dose chemotherapy (HDCT) with autologous hematopoetic stem cell rescue. However, this method has a high risk of acute and delayed toxicity, and, sometimes doesn’t meet the expected effectiveness. This confirms the necessity of more considerate approach for choosing the category of patients for this therapeutic option with the determination of the most significant factors on the part of the patient and the type of malignant tumor.Objective. Analysis of the results of HDCT with autologous hematopoetic stem cell transplantation (HSCT) in children with high-risk solid malignancies, conducted in the Department of pediatric oncohematology and BMT of the Federal State Budgetary Institution “V.A. Almazov National Medical Research Center”.Design and methods. We perform a retrospective analysis of 55 cycles of HDCT with autologous hematopoetic stem cell rescue provided from 2017 to 2020 in 39 patients with high-risk malignant tumors. The toxicity and efficacy of the method were assessed taking into account the frequency of infectious complications, early post-transplant mortality, event-free (EFS) and overall survival (OS).Results. The predominant category of patients were children with CNS tumors (61.5 %). Mean age of the patients was 2 years 9 months. At the time of HDCT 35.9% of patients were in complete remission (CR), 64.1 % had signs of active disease (AD). In 59% of patients, one course of HDCT was performed, in 41 % — tandem transplantation was performed according to the recommendations of the protocol for the treatment of the disease. The most common conditioning regimen was carboplatin + etoposide (27.3 %). The predominant source of hematopoietic stem cells were peripheral stem cells (87.3 %). The frequency of infectious complications in the post-transplant period was 100 %, neutropenic enterocolitis (61.8 %) and febrile neutropenia (34.5 %) were predominant. A high frequency of reactivation of CMV infection (25.4 %) was noted, meanwhile CMV disease occurred in 35.7 % of cases. The most important prognostic factor was the disease status at the time of HDCT. 2-year OS incidence of 85.7 % vs 65.3% and EFS 85.7 % vs 39 % in patients with CR and AD respectively. After completing the course of HDCT with autologous HSCT 94.8 % of patients continued anticancer therapy.Conclusion. HDCT with autologous HSCT demonstrates a satisfactory toxicity profile and can improve OS and EFS in children with high-risk malignant tumors. A reliable prognostic factor that determines the effectiveness of the method is the disease status at the time of HDCT.