实体恶性肿瘤患儿接受大剂量化疗后进行自体造血干细胞移植的并发症:单中心经验

T. Z. Aliev, K. Kirgizov, E. Machneva, I. Kostareva, K. Sergeenko, D. S. Smirnova, N. Burlaka, Yu. V. Lozovan, I. Y. Trushkova, A. Elfimova, K. V. Mitrakov, T. I. Potemkina, M. D. Malova, R. R. Fatkhullin, N. Stepanyan, D. A. Kapkova, G. Sagoyan, A. M. Suleymanova, N. Matinyan, G. Muftakhova, A. P. Kazantsev, O. M. Romantsova, M. Rubanskaya, T. Ushakova, A. Rodina, V. V. Zhogov, V. S. Vanesyan, Y. Skvortsova, I. Kazantsev, A. S. Slinin, T. Gorbunova, T. T. Valiev, V. G. Polyakov, S. Varfolomeeva
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引用次数: 0

摘要

高剂量化疗(HDCT)后进行自体造血干细胞移植(auto-HSCT)是一种治疗方法,可增强高危恶性肿瘤患者的抗肿瘤效果。然而,尽管这种方法很有效,但在移植后早期和晚期出现感染和毒性并发症的风险要高于按照标准方案进行治疗的相关风险,而且会显著恶化移植效果。我们对 2020-2023 年在俄罗斯联邦医疗保健部 N.N. Blokhin 国家肿瘤学医学研究中心 L.A. Durnov 儿童肿瘤学和血液学研究所接受治疗的 156 例高风险实体瘤患者进行了自体 HSCT 结果回顾性分析。该研究获得了独立伦理委员会和N.N. Blokhin国家肿瘤学医学研究中心科学委员会的批准。研究对象包括78名男孩(50%)和78名女孩(50%),患者年龄中位数为8岁7个月(9个月-17岁8个月)。90名(57.7%)神经母细胞瘤患者、25名(16.0%)尤文肉瘤患者、16名(10.3%)生殖细胞瘤患者、13名(8.4%)肾母细胞瘤患者、7名(4.5%)视网膜母细胞瘤患者、3名(1.9%)髓母细胞瘤患者、1名(0.6%)胸膜肺泡瘤患者和1名(0.6%)矽肺母细胞瘤患者接受了自体造血干细胞移植。我们采用了以下调理方案:曲硫散+美法仑(n=116)、卡铂+硫代百部+依托泊苷(n=17)、美法仑(n=13)、卡铂+硫代百部+依托泊苷+环磷酰胺(n=10)。根据临床适应症和采用的治疗方案,136 例(87.2%)患者接受了一个疗程的 HDCT 治疗,20 例(12.8%)患者接受了串联 HDCT 治疗。在大多数患者中,粒细胞和血小板的中位恢复时间分别为 11(8-19)天和 14(12-21)天。自体血液透析后患者最常见的感染性并发症是粘膜炎(89.1%)、中性粒细胞减少性小肠结肠炎(76.9%)、发热性中性粒细胞减少症(71.2%),较少见的有:导管相关性血流感染(9%)、肺炎(14.1%)、急性呼吸窘迫综合征(0.6%)。至于毒性并发症,所有患者都有催吐综合征,98人(62.8%)有皮肤毒性,9人(5.8%)有出血性膀胱炎,116人(74.3%)有肝毒性,14人(9%)有神经毒性,102人(65.4%)有中度营养不良。44.2%的患者因血小板减少而出现出血性综合征。自体供血干细胞移植后,大多数患者都会出现化疗引起的并发症(包括感染性并发症),这些并发症不仅会严重影响患者的健康和生活质量,还会根据严重程度对患者的生命构成威胁。正确选择调理方案、有效采集造血干细胞、复杂的配套治疗、及时诊断和治疗并发症,可显著改善高危实体瘤儿童的自体血液透析治疗效果。
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Complications of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation in children with solid malignant neoplasms: a single-center experience
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.
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来源期刊
Pediatric Hematology/Oncology and Immunopathology
Pediatric Hematology/Oncology and Immunopathology Medicine-Pediatrics, Perinatology and Child Health
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