Current status and influencing factors analysis of adverse reactions in hematopoietic stem cell infusion
-
摘要:
目的 调查造血干细胞输注不良反应发生现状及其影响因素, 为构建造血干细胞安全输注方案提供依据。 方法 选择2017年1月—2022年7月在浙江省某三级甲等医院骨髓移植中心行造血干细胞移植的389例血液病患者作为调查对象，使用一般资料调查表和不良反应调查表收集相关资料。 结果 本研究389例接受造血干细胞输注患者的不良反应发生率为31.11%(121/389)，其中异体移植患者不良反应反生率为34.04%(97/285)，自体移植患者不良反应发生率为23.08%(24/104)；不良反应事件中心血管系统发生率最高(89次，占所有不良反应事件的52.35%)。单因素分析结果显示，年龄、性别、移植类型、干细胞来源、供受体人类白细胞抗原配型相合度、CD34+细胞数、输注速率是造血干细胞输注不良反应发生的影响因素(均P < 0.05)。多因素logistic回归分析结果显示，年龄大(OR=1.121，P＜0.001)、干细胞来源(骨髓干细胞，OR=2.836，P=0.007)、供受体人类白细胞抗原配型不全相合(OR=0.110，P＜0.001)、干细胞输注速率快(OR=2.107，P＜0.001)是造血干细胞输注不良反应发生的独立危险因素。 结论 造血干细胞输注不良反应发生率较高，年龄大、骨髓干细胞输注、供受体人类白细胞抗原配型不全相合、干细胞输注速率是其影响因素，应给予预防性干预措施，以降低造血干细胞输注不良反应的发生率。 Abstract:Objective To investigate the current situation and influencing factors of adverse reactions of hematopoietic stem cell infusion, and to provide a basis for the construction of a safe infusion program for hematopoietic stem cells. Methods A total of 389 patients with hematological diseases who underwent hematopoietic stem cell transplantation at a tertiary Grade A hospital's Bone Marrow Transplantation Center in Zhejiang Province between January 2017 and July 2022 were selected as the study population. Data collection involved the use of general information questionnaire and adverse reaction assessment forms. Results Among the 389 patients who underwent hematopoietic stem cell infusion, the overall incidence of adverse reactions was 31.11% (121/389). Specially, allogeneic transplant recipients experienced an incidence of 34.04% (97/285), while autologous transplant recipients had an incidence of 23.08% (24/104). The cardiovascular system exhibited the highest occurrence of adverse reactions, accounting for 89 cases (52.35% of all adverse events). Univariate analysis showed that age, gender, transplantation type, stem cell source, human leukocyte antigen matching, CD34+ cell count, and infusion rate significantly influenced adverse reactions in hematopoietic stem cell transplantation (all P < 0.05). Furthermore, multivariate logistic regression analysis identified older age (OR=1.121, P < 0.001), stem cell source (bone marrow stem cell, OR=2.836, P=0.007), human leukocyte antigen mismatch between donor and recipient (OR=0.110, P < 0.001), and fast infusion rate of stem cell (OR=2.107, P < 0.001) as independent risk factors for adverse reactions of hematopoietic stem cell transplantation. Conclusion The occurrence in adverse reactions of hematopoietic stem cell infusion is relatively high with older age, bone marrow fast infusion rate of stem cell, incomplete human leukocyte antigen matching between donor and recipient, and high infusion rate identified as influencing factors. Preventive interventions should be implemented to reduce the occurrence of adverse reactions in hematopoietic stem cell infusion. -
表 1 异体移植与自体移植血液病患者一般资料比较
Table 1. Comparison of general information between allotransplantation and autotransplantation in patients with hematological diseases
组别 例数 性别
(男性/女性，例)年龄
(x±s，岁)体重
(x±s，kg)诊断(再生障碍性贫血/白血病/淋巴瘤/骨髓增生异常综合征/多发性骨髓瘤/其他，例) 异体移植 285 141/144 34.92±13.20 58.73±13.53 169/62/5/43/0/6 自体移植 104 62/42 39.08±12.74 62.89±11.07 0/5/82/0/16/1 统计量 3.141a 2.773b 2.814b 357.277a P值 0.076 0.006 0.005 ＜0.001 注：a为χ2值，b为t值。 
下载: 导出CSV
表 2 异体移植与自体移植血液病患者造血干细胞输注不良反应发生情况比较[次(%)]
Table 2. Comparative analysis of adverse reactions following hematopoietic stem cell transfusion in patients with blood diseases after allotransplantation and autologous transplantation [times(%)]
组别 次数 心血管系统反应 神经系统反应 呼吸系统反应 发热反应 泌尿系统反应 消化系统反应 皮疹、瘙痒 异体移植 135 75(55.56) 19(14.07) 10(7.41) 15(11.11) 4(2.96) 8(5.93) 4(2.96) 自体移植 35 14(40.00) 0 10(28.57) 3(8.57) 6(17.14) 2(5.72) 0 χ2值 2.696 11.993 0.016 7.696 ＜0.001 P值 0.101 0.014a 0.001 0.899 0.006 0.999 0.582a 注：a为使用Fisher精确检验。
下载: 导出CSV
表 3 造血干细胞输注不良反应发生的单因素分析
Table 3. Analysis of adverse reactions in hematopoietic stem cell infusion using single-factor approach
组别 例数 性别
(男性/女性，例)年龄
(x±s，岁)体重
(x±s，kg)是否第一次移植
(是/否，例)移植类型
(异体/自体，例)诊断(再生障碍性贫血/白血病/淋巴瘤/骨髓增生异常综合征/多发性骨髓瘤/其他，例) 发生不良反应组 121 54/67 45.57±9.39 58.60±13.52 119/2 97/24 57/21/20/16/4/3 未发生不良反应组 268 149/119 31.73±12.39 60.40±12.79 265/3 188/80 112/46/67/27/12/4 统计量 4.020a 12.139b 1.262b ＜0.001a 4.270a 4.898a P值 0.045 ＜0.001 0.208 0.999 0.039 0.427 组别 例数 HLA配型相合度
(全相合/不全相合，例)供受体ABO血型相合度
(相合/不相合，例)预处理方案(清髓/非清髓/减低剂量，例) 干细胞来源
(外周血/骨髓/脐血，例)供者来源
(无关/亲缘/自体，例)发生不良反应组 121 27/94 92/29 69/9/43 56/50/15 16/81/24 未发生不良反应组 268 182/86 212/56 158/14/96 192/50/26 30/158/80 统计量 69.713a 0.461a 0.746a 25.644a 4.284a P值 ＜0.001 0.497 0.689 ＜0.001 0.117 组别 例数 CD34+细胞数
[M(P25, P75), ×106/kg]TNC计数
[M(P25, P75), ×108/kg]干细胞总体积
[M(P25, P75), mL]输注时间
[M(P25, P75), min]输注速率
[M(P25, P75), mL/min]发生不良反应组 121 4.41(1.97, 7.87) 7.36(5.20, 10.48) 600.00(199.00, 1 000.00) 160.00(70.00, 341.00) 2.90(2.33, 3.87) 未发生不良反应组 268 5.33(2.99, 9.06) 7.70(5.90, 10.32) 279.50(200.00, 800.00) 150.00(90.00, 260.00) 2.25(1.78, 2.97) 统计量 -2.030c -1.156c -1.927c -0.369c -5.110c P值 0.042 0.248 0.054 0.712 ＜0.001 注：a为χ2值，b为t值，c为Z值。
下载: 导出CSV
表 4 变量赋值情况
Table 4. Status of variable assignments
变量 赋值方法 性别 男性=1，女性=2 移植类型 异体移植=1，自体移植=2 干细胞来源 外周血干细胞=(0，0，0)，骨髓干细胞=(0，1，0)，脐血干细胞=(0，0，1) HLA配型相合度 HLA配型全相合=1，HLA配型不全相合=2 年龄 以实际值赋值 CD34+细胞数 以实际值赋值 输注速率 以实际值赋值
下载: 导出CSV
表 5 造血干细胞输注不良反应发生的多因素分析
Table 5. Multivariate analysis of adverse reactions following hematopoietic stem cell infusion
变量 B SE Wald χ2 P值 OR值 95% CI 年龄 0.114 0.016 53.537 ＜0.001 1.121 1.087~1.156 骨髓干细胞(以外周血干细胞为参照) 1.042 0.387 7.257 0.007 2.836 1.328~6.055 HLA配型相合度 -2.203 0.396 30.936 ＜0.001 0.110 0.051~0.240 输注速率 0.745 0.150 24.834 ＜0.001 2.107 1.572~2.825
下载: 导出CSV
表 6 异体移植血液病患者造血干细胞输注不良反应发生的影响因素分析
Table 6. Analysis of factors influencing adverse reactions in allogeneic transplantation patients receiving hematopoietic stem cell transfusion
组别 例数 性别
(男性/女性，例)年龄
(x±s，岁)体重
(x±s，kg)诊断(再生障碍性贫血/白血病/淋巴瘤/骨髓增生异常综合征/多发性骨髓瘤/其他，例) CD34+细胞数
[M(P25, P75), ×106/kg]发生不良反应组 97 41/56 44.87±9.63 58.22±13.82 57/20/1/16/0/3 3.54(1.88, 7.76) 未发生不良反应组 188 100/88 29.79±11.80 58.99±13.41 113/42/4/27/0/2 4.67(2.52, 7.99) 统计量 3.054a 11.576b 0.459b 2.211a -1.571c P值 0.081 ＜0.001 0.646 0.724 0.116 组别 例数 TNC计数
[M(P25, P75), ×108/kg]干细胞总体积
[M(P25, P75), mL]输注时间
[M(P25, P75), min]输注速率
[M(P25, P75), mL/min]发生不良反应组 97 7.40(5.28, 11.54) 285.00(165.00, 1 000.00) 135.00(55.50, 355.00) 2.64(2.20, 3.39) 未发生不良反应组 188 8.04(5.99, 11.80) 230.00(176.00, 582.50) 115.00(80.00, 243.75) 2.10(1.60, 2.53) 统计量 -1.103c -1.890c -0.704c -5.686c P值 0.270 0.059 0.481 ＜0.001 注：a为χ2值，b为t值，c为Z值。
下载: 导出CSV
表 7 自体移植血液病患者造血干细胞输注不良反应发生的影响因素分析
Table 7. Analysis of factors influencing adverse reactions in autologous transplantation patients receiving hematopoietic stem cell infusion
组别 例数 性别
(男性/女性，例)年龄
(x±s，岁)体重
(x±s，kg)诊断(再生障碍性贫血/白血病/淋巴瘤/骨髓增生异常综合征/多发性骨髓瘤/其他，例) 发生不良反应组 24 13/11 48.42±7.90 60.17±12.43 0/1/19/0/4/0 未发生不良反应组 80 49/31 36.28±12.61 63.71±10.58 0/4/63/0/13/0 统计量 0.385a 5.669b 1.382b 0.159a P值 0.535 ＜0.001 0.170 0.999 组别 例数 CD34+细胞数
[M(P25, P75), ×106/kg]TNC计数
[M(P25, P75), ×108/kg]干细胞总体积
[M(P25, P75), mL]输注时间
[M(P25, P75), min]输注速率
[M(P25, P75), mL/min]发生不良反应组 24 6.48(3.56, 9.84) 6.20(4.55, 9.52) 723.50(585.00, 1 000.00) 160.00(140.00, 247.50) 4.69(3.05, 5.70) 未发生不良反应组 80 7.26(4.51, 10.30) 7.22(5.87, 9.19) 665.00(473.75, 905.25) 200.00(160.00, 264.25) 2.88(2.46, 3.74) 统计量 -0.498c -1.030c -1.320c -1.483c -3.341c P值 0.619 0.303 0.187 0.138 0.001 注：a为χ2值，b为t值，c为Z值。
下载: 导出CSV
-
[1] NAKAMURA Z M, NASH R P, QUILLEN L J, et al. Psychiatric care in hematopoietic stem cell transplantation[J]. Psychosomatics, 2019, 60(3): 227-237. doi: 10.1016/j.psym.2019.01.005 [2] 中华医学会血液学分会干细胞应用学组. 中国异基因造血干细胞移植治疗血液系统疾病专家共识(Ⅲ): 急性移植物抗宿主病(2020年版)[J]. 中华血液学杂志, 2020, 41(7): 529-536.Stem cell Application Group, Society of Hematology, Chinese Medical Association. Chinese consensus of allogeneic hematopoietic stem cell transplantation for hematological disease(Ⅲ)—acute graft-versus-host disease(2020)[J]. Chinese Journal of Hematology, 2020, 41(7): 529-536. [3] 张莺莺, 潘萍, 李瑶, 等. 接纳承诺护理疗法在造血干细胞移植患者中的应用效果[J]. 中华现代护理杂志, 2021, 27(4): 512-516.ZHANG Y Y, PAN P, LI Y, et al. Application effect of acceptance and commitment nursing therapy in patients with hematopoietic stem cell transplantation[J]. Chinese Journal of Modern Nursing, 2021, 27(4): 512-516. [4] 王营营. 造血干细胞移植患者心理韧性的影响因素及中介效应分析[D]. 合肥: 安徽医科大学, 2019.WANG Y Y. Analysis of influencing factors and mediating effects of mental toughness in patients with hematopoietic stem cell transplantation[D]. Hefei: Anhui Medical University, 2019. [5] SAAD A, DE LIMA M, ANAND S, et al. Hematopoietic cell transplantation, version 2.2020, nccn clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2020, 18(5): 599-634. doi: 10.6004/jnccn.2020.0021 [6] IKEDA K, OHTO H, OKUYAMA Y, et al. Adverse events associated with infusion of hematopoietic stem cell products: a prospective and multicenter surveillance study[J]. Transfus Med Rev, 2018, 39: 382. [7] IKEDA K, OHTO H, YAMADA-FUJIWARA M, et al. Hematopoietic cell infusion-related adverse events in pediatric/small recipients in a prospective/multicenter study[J]. Transfusion, 2020, 60(5): 1015-1023. doi: 10.1111/trf.15786 [8] 张红, 李凤霞, 王艳平, 等. 血液病患者脐血干细胞输入3小时内不良反应观察与分析[J]. 护理学杂志, 2021, 36(21): 32-34. doi: 10.3870/j.issn.1001-4152.2021.21.032ZHANG H, LI F X, WANG Y P, et al. Observation and analysis of adverse reactions occurring within 3 hours of infusion of umbilical cord blood-derived mesenchymal stem cells in patients with hematologic diseases[J]. Journal of Nursing Science, 2021, 36(21): 32-34. doi: 10.3870/j.issn.1001-4152.2021.21.032 [9] VIDULA N, VILLA M, HELENOWSKI I B, et al. Adverse events during hematopoietic stem cell infusion: analysis of the infusion product[J]. Clin Lymphoma Myeloma Leuk, 2015, 15(11): 157-162. doi: 10.1016/j.clml.2015.08.085 [10] Cancer Therapy Evaluation Program. Common terminology criteria for adverse events[EB/OL]. [2021-04-19]. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm#ctc_60 .[11] KOLLERUP MADSEN B, HILSCHER M, ZETNER D, et al. Adverse reactions of dimethyl sulfoxide in humans: a systematic review[J]. F1000Res, 2018, 7: 1746. DOI: 10.12688/f1000research.16642.2. [12] WENG L, BEAUCHESNE P R. Dimethyl sulfoxide-free cryopreservation for cell therapy: a review[J]. Cryobiology, 2020, 94: 9-17. doi: 10.1016/j.cryobiol.2020.03.012 [13] GILFANOVA R, CALLEGARI A, CHILDS A, et al. A bioinspired and chemically defined alternative to dimethyl sulfoxide for the cryopreservation of human hematopoietic stem cells[J]. Bone Marrow Transpl, 2021, 56(11): 2644-2650. doi: 10.1038/s41409-021-01368-w [14] 吕素玲, 林向东, 陈茹, 等. 老年血液透析患者自我管理能力对跌倒恐惧的影响研究[J]. 中华全科医学, 2022, 20(8): 1343-1345, 1379. doi: 10.16766/j.cnki.issn.1674-4152.002592LYU S L, LIN X D, CHEN R, et al. Effect of self-management ability on fall fear in elderly patients undergoing haemodialysis[J]. Chinese Journal of General Practice, 2022, 20(8): 1343-1345, 1379. doi: 10.16766/j.cnki.issn.1674-4152.002592 [15] 谭树凤, 沈红卫, 李桃, 等. 上海市浦东新区某社区老年人群体检结果及5年随访分析[J]. 中华全科医学, 2022, 20(10): 1715-1717, 1785. doi: 10.16766/j.cnki.issn.1674-4152.002687TAN S F, SHEN H W, LI T, et al. Healthy examination results and 5-year follow-up analysis of the elderly in a community of Pudong New Area, Shanghai[J]. Chinese Journal of General Practice, 2022, 20(10): 1715-1717, 1785. doi: 10.16766/j.cnki.issn.1674-4152.002687 [16] 姬长珍, 王慧媛, 毛显春. 老年住院患者营养状况与衰弱关系的研究[J]. 北京医学, 2021, 43(11): 1123-1125.JI C Z, WANG H Y, MAO X C. Relationship between frailty and malnutrition in elderly inpatients[J]. Beijing Medical Journal, 2021, 43(11): 1123-1125. [17] 党红星, 许峰. 输血相关的循环超负荷及急性肺损伤[J]. 中国实用儿科杂志, 2020, 35(12): 947-953.DANG H X, XU F. Transfusion-associated circulatory overload and transfusion-related acute lung injury[J]. Chinese Journal of Practical Pediatrics, 2020, 35(12): 947-953. [18] KISSOON T, GODDER K, FORT J. Infusion of hematopoietic stem cell products using pump mechanism: an approach worth consideration[J]. J Pediatr Hematol Oncol, 2020, 42(3): e174-e176. doi: 10.1097/MPH.0000000000001491 [19] KIDERLEN TR, RONNEBURGER L, MARRETTA L, et al. Retrospective comparison of reinfusion procedures and subsequent leukopenia in autologous stem cell transplantation[J]. Int J Hematol, 2021, 114(4): 459-463. doi: 10.1007/s12185-021-03196-6 [20] KLANDERMAN R B, WIJNBERGE M, BOSBOOM J J, et al. Differential effects of speed and volume on transfusion-associated circulatory overload: a randomized study in rats[J]. Vox Sang, 2022, 117(3): 371-378. doi: 10.1111/vox.13191 -
点击查看大图
表(7)
计量
- 文章访问数: 334
- HTML全文浏览量: 121
- PDF下载量: 13
- 被引次数: 0
