Complications of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation in children with solid malignant neoplasms: a single-center experience
Authors: Aliev T. Z. , Kirgizov K. I. , Machneva E. B. , Kostareva I. O. , Sergeenko K. A. , Smirnova D. S. , Burlaka N. A. , Lozovan Yu. V. , Trushkova I. Yu. , Elfimova A. Yu. , Mitrakov K. V. , Potemkina T. I. , Malova M. D. , Fatkhullin R. R. , Stepanyan N. G. , Kapkova D. A. , Sagoyan G. B. , Suleymanova A. M. , Matinyan N. V. , Muftakhova G. M. , Kazantsev A. P. , Romantsova O. M. , Rubanskaya M. V. , Ushakova T. L. , Rodina A. D. , Zhogov V. V. , Vanesyan V. Sh. , Skvortsova Yu. V. , Kazantsev I. V. , Slinin A. S. , Gorbunova T. V. , Valiev T. T. , Polyakov V. G. , Varfolomeeva S. R. 
Published: July 2024

High-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is a therapeutic option that allows potentiating the antitumor effect in patients with malignant neoplasms (MNs) belonging to the high-risk group. However, despite the effectiveness of this method, the risks of developing infectious and toxic complications in the early and late post-transplantation period are higher than the risks associated with treatment according to standard protocols and can significantly worsen the results of transplantation. We carried out a retrospective analysis of the results of auto-HSCT in a cohort of 156 patients with high-risk solid MNs treated at the L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation in 2020–2023. The study was approved by the Independent Ethics Committee and the Scientific Council of the N.N. Blokhin National Medical Research Center of Oncology. The study included 78 (50%) boys and 78 (50%) girls, the median age of the patients was 8 years 7 months (9 months – 17 years 8 months). Auto-HSCT was performed in 90 (57.7%) patients with neuroblastoma, 25 (16.0%) – with Ewing's sarcoma, 16 (10.3%) – with germ cell tumors, 13 (8.4%) – with nephroblastoma, 7 (4.5%) – with retinoblastoma, 3 (1.9%) – with medulloblastoma, 1 (0.6%) patient with pleuropulmonary blastoma and 1 (0.6%) patient with sialoblastoma. We used the following conditioning regimens: treosulfan + melphalan (n = 116), carboplatin + thiotepa + etoposide (n = 17), melphalan (n = 13), carboplatin + thiotepa + etoposide + cyclophosphamide (n = 10). Depending on the clinical indications and the treatment protocol used, 136 (87.2%) patients underwent one course of HDCT, and 20 (12.8%) patients underwent tandem HDCT. In most patients, the median recovery time for granulocytes and platelets was 11 (8–19) days and 14 (12–21) days, respectively. The most common infectious complications in patients after auto-HSCT were mucositis (89.1%), neutropenic enterocolitis (76.9%), febrile neutropenia (71.2%), less often: catheter-associated bloodstream infection (9%), pneumonia (14.1%), acute respiratory distress syndrome (0.6%). As regards toxic complications, all patients had emetic syndrome, 98 (62.8%) had dermatological toxicity, 9 (5.8%) had hemorrhagic cystitis, 116 (74.3%) had hepatic toxicity, 14 (9%) had neurotoxicity, 102 (65.4%) had moderate nutritional insufficiency. Episodes of hemorrhagic syndrome due to thrombocytopenia were observed in 44.2% of patients. After auto-HSCT, most patients develop chemotherapy-induced (including infectious) complications, which can not only significantly disrupt the patients’ well-being and quality of life, but also, depending on the severity, pose a threat to their life. The correct choice of conditioning regimen, effective collection of hematopoietic stem cells, complex accompanying therapy, timely diagnosis and treatment of complications can significantly improve the results of auto-HSCT in children with high-risk solid MNs.