SAFETY AND EFFECTIVENESS ASSESSMENT OF THE HEMATOPOIETIC STEM CELL MOBILIZATION AND COLLECTION METHOD IN CHILDREN FROM DIFFERENT AGE GROUPS WITH MALIGNANT NEOPLASMS. A SINGLE-CENTER EXPERIENCE

N. Stepanyan, K. Kirgizov, E. Machneva, R. R. Fatkhullin, T. Z. Aliev, I. Kostareva, A. P. Kazantsev, N. Matinyan, V.V. Zhogov, M. Rubanskaya, O. Romantsova, N. Batmanova, T. T. Valiev, T. Gorbunova, V. Polyakov, S. Varfolomeeva
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引用次数: 0

Abstract

High dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) is used currently as a consolidating stage in cancer treatment protocols for children from different age groups with various malignant neoplasms. Auto-HSCT can improve both progression-free survival and overall survival of such patients. At the same time the optimization of the collection of autologous hematopoietic stem cells (HSCs) seems to be an important factor in the successful implementation of auto-HSCT. The purpose of this research was to evaluate the safety and effectiveness of the HSCs mobilization and collection method in children from different age groups with various malignancies. Materials and methods used: a single-center retrospective cohort study of 258 pediatric patients (median body weight 20.0 [13.8; 42.0] (7.0-95.0) kg and median height 116 [97; 155] (55.0-189) cm) with various cancers aged 1 to 18 y/o (median 78.0 [36; 144] (3-215) months old) who received treatment in Jan. 2020-Jan. 2023 at the Research Institute of Pediatric Oncology and Hematology named after Academician L.A. Durnov with the N.N. Blokhin Russian Cancer Research Center (Moscow, Russia). Patients were divided into 3 age groups: younger than 1 y/o, 1 to 10 y/o and 11 to 18 y/o. Results: 242 (93.8%) of HSC apheresis procedures were successful on the first attempt, 16 patients underwent repeated apheresis (a total of 274 procedures were performed). The median number of CD34+ cells obtained was 110.95 [45.6; 276.4] (0.70-2338.2) cells/µl, median apheresis duration was 253.5 [189; 338] (82-575) min. No serious complications were observed during the HSCs mobilization and collection in any patient. None of the patients developed hemodynamic disturbances. The main criteria for effectiveness was the CD34+/kg level, the median of which was 5.1 [2.4; 12.7] (0.01-95.6)•106. One of the safety criteria for the patients from all the three age groups was the absence of hemodynamic disorders and citrate reactions in the form of numbness, cyanosis of the skin and respiratory disorders. Another important safety criteria were the absence of a significant decrease in both platelet and hemoglobin levels. The median platelet levels prior to the procedure was 125.5 [68; 210] (14.0-815)•109/l and 129 [73; 210] (17.0-823)•109/l at the end of the procedure (p<0.001). Hemoglobin levels before and after the procedure were 100 [94; 110] (75-242) g/l and 99 [93; 109] (70-142) g/l, respectively (p<0.001). Considering it safe to reduce hemoglobin (g/l) and/or platelets (•109/l) by no more than 10 units in each measurement, in 87.6±4.1% (83.0-91.1) of observed cases the procedure was safe without statistically significant differences in all age groups. The effectiveness of the HSCs mobilization and collection method proposed by the Authors in children of the older age group (11 to 18 y/o) was the lowest and was statistically significantly different from the effectiveness in the group of children aged 1 to 10 y/o (p<0.001) with cancer and amounted to 84.5±4.4% (79.6-88.4). Conclusion: with the multidisciplinary team of practitioners, HSC apheresis in children is a safe and effective technique used as part of the complex cancer treatment in patients from poor prognosis groups. The apheresis algorithm that the Authors have proposed allows high-quality collection of CD34+ positive cells in amounts sufficient for further auto-HSCT.
不同年龄组恶性肿瘤儿童造血干细胞动员和采集方法的安全性和有效性评估。单中心经验
目前,大剂量化疗(HDCT)联合自体造血干细胞移植(Auto-HSCT)作为癌症治疗方案的巩固阶段,被用于治疗不同年龄组的各种恶性肿瘤儿童。自体造血干细胞移植可提高此类患者的无进展生存期和总生存期。同时,优化自体造血干细胞(HSCs)的采集似乎也是成功实施自体造血干细胞移植的一个重要因素。本研究的目的是评估在不同年龄组患有各种恶性肿瘤的儿童中动员和采集造血干细胞方法的安全性和有效性。采用的材料和方法:一项单中心回顾性队列研究,研究对象为 258 名 1 至 18 岁患有各种癌症的儿童患者(中位体重 20.0 [13.8; 42.0] (7.0-95.0) kg,中位身高 116 [97; 155] (55.0-189) cm)(中位 78.这些患者于 2020 年 1 月至 2023 年 1 月在以列-阿-杜尔诺夫院士命名的儿科肿瘤学和血液学研究所(Research Institute of Pediatric Oncology and Hematology)和 N.N. Blokhin 俄罗斯癌症研究中心(Russian Cancer Research Center)(俄罗斯,莫斯科)接受治疗。)患者分为三个年龄组:1岁以下、1至10岁和11至18岁。结果:242例(93.8%)造血干细胞分离手术首次成功,16例患者重复进行了分离手术(共进行了274例)。获得的 CD34+ 细胞中位数为 110.95 [45.6; 276.4] (0.70-2338.2) 个/微升,中位无细胞滞留时间为 253.5 [189; 338] (82-575) 分钟。在动员和收集造血干细胞的过程中,没有发现任何患者出现严重并发症。没有一名患者出现血液动力学紊乱。有效性的主要标准是 CD34+/kg 水平,中位数为 5.1 [2.4; 12.7] (0.01-95.6)-106。所有三个年龄组患者的安全标准之一是没有血液动力学紊乱和以麻木、皮肤发绀和呼吸紊乱为表现形式的枸橼酸盐反应。另一个重要的安全标准是血小板和血红蛋白水平均无明显下降。手术前血小板水平中位数为 125.5 [68; 210] (14.0-815)-109/升,手术结束时为 129 [73; 210] (17.0-823)-109/升(P<0.001)。手术前后的血红蛋白水平分别为 100 [94; 110] (75-242) 克/升和 99 [93; 109] (70-142) 克/升(P<0.001)。考虑到血红蛋白(克/升)和/或血小板(-109/升)每次减少不超过10个单位是安全的,在87.6±4.1%(83.0-91.1)的观察病例中,手术是安全的,所有年龄组的差异无统计学意义。作者提出的造血干细胞动员和收集方法对年龄较大的儿童(11 至 18 岁)的有效性最低,与 1 至 10 岁癌症儿童组的有效性有显著统计学差异(p<0.001),达到 84.5±4.4% (79.6-88.4)。结论:在多学科医生团队的合作下,儿童造血干细胞穿刺是一项安全有效的技术,可作为预后不良组患者复杂癌症治疗的一部分。作者提出的造血干细胞采集算法可以高质量地采集到足够数量的CD34+阳性细胞,用于进一步的自体造血干细胞移植。
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