The combined application of long- and short-acting granulocyte colony-stimulating factor improved the excellent rate of autologous peripheral blood hematopoietic stem cell collection
-
摘要: 目的 比较长短效粒细胞集落刺激因子(G-CSF)联合[聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)+G-CSF]、化疗联合短效G-CSF以及单用短效G-CSF动员方案在患者自体外周血造血干细胞动员、采集及移植后造血重建中的差异，以期获得更有效的动员方案。方法 收集2019年2月—2022年2月我院血液科71例恶性血液系统疾病行自体外周血造血干细胞移植患者的临床数据进行前瞻性研究。将长短效G-CSF联合(PEG-rhG-CSF+G-CSF组，12例)、化疗联合短效G-CSF(化疗+G-CSF组，34例)以及单用短效G-CSF(单用G-CSF组，25例)3种动员方案对采集细胞数、成功率、移植后造血重建时间结果进行比较，并对影响动员疗效的因素进行统计分析。结果 3组在采集CD34+细胞数、采集优良率、造血重建时间方面比较差异有统计学意义(P < 0.05)。PEG-rhG-CSF+G-CSF组采集CD34+细胞数[(15.77±5.44)×106/kg vs (4.30±0.59)×106/kg，P=0.001]、采集优良率(100.0% vs 32.0%，P=0.001)显著优于单用G-CSF组，且PEG-rhG-CSF+G-CSF组采集CD34+细胞数[(15.77±5.44)×106/kg vs (8.34±0.94)×106/kg，P=0.034]、采集优良率(100.0% vs 73.5%，P=0.049)明显优于化疗+G-CSF组。在造血重建方面，PEG-rhG-CSF+G-CSF组粒细胞恢复时间[(10.25±0.78) d vs (12.56±0.69) d，P=0.042]及血小板恢复时间[(10.42±0.41) d vs (12.68±0.70) d，P=0.035]明显优于单用G-CSF组，且PEG-rhG-CSF+G-CSF组粒细胞恢复时间[(10.25±0.78) d vs (13.68±0.42) d，P=0.001]及血小板恢复时间[(10.42±0.41) d vs (13.15±0.41) d，P=0.007]明显优于化疗+G-CSF组。3组间采集成功率比较差异无统计学意义(P>0.05)。所有患者移植后均顺利获得造血重建，无移植相关死亡。结论 长短效G-CSF联合动员方案与化疗+G-CSF及单用G-CSF动员方案相比，CD34+细胞采集数及采集优良率更高，造血重建时间明显缩短，该动员方案可作为恶性血液系统疾病患者自体外周血动员的一项较好选择。
-
关键词:
- 自体外周血造血干细胞移植 /
- 动员 /
- PEG-rhG-CSF /
- 粒细胞集落刺激因子 /
- 采集优良率
Abstract: Objective To compare the differences in mobilization, collection, and post-transplant hematopoietic reconstitution of autologous peripheral blood hematopoietic stem cells among the long- and short-acting granulocyte colony-stimulating factor (G-CSF) combined regimen(pegylated recombinant human granulocyte colony-stimulating factor [PEG-rhG-CSF]+G-CSF), chemotherapy combined with short-acting G-CSF and short-acting G-CSF alone, and figure out which one is more effective.Methods The clinical data of 71 patients underwent peripheral blood hematopoietic stem cell transplantation from February 2019 to February 2022 were collected. The results of number of collected cells, success rate and time to hematopoietic reconstruction after transplantation were compared, including long- and short-term G-CSF combined regimen(PEG-rhG-CSF+G-CSF group, n=12), chemotherapy combined with short-term G-CSF (chemotherapy+G-CSF group, n=34), and short-term G-CSF alone (G-CSF group, n=25), and the factors affecting the efficacy of mobilization were analyzed.Results There were significant differences in the number of CD34+cells, excellent rate of collection, and hematopoietic reconstruction time among the three groups(P < 0.05). The number of CD34+cells collected ([15.77±5.44]×106/kg vs [4.30±0.59]×106/kg, P=0.001) and the excellent rate(100.0% vs 32.0%, P=0.001) in the PEG-rhG-CSF+G-CSF group were significantly better than those in the G-CSF group, and the number of CD34+cells collected ([15.77±5.44]×106/kg vs [8.34±0.94]×106/kg, P=0.034) and the excellent rate (100.0% vs 73.5%, P=0.049) in the PEG-rhG-CSF+G-CSF group were better than those in the chemotherapy+G-CSF group. In terms of hematopoietic reconstruction, the granulocyte recovery time ([10.25±0.78]d vs [12.56±0.69]d, P=0.042) and the platelet recovery time ([10.42±0.41]d vs [12.68±0.70]d, P=0.035) in the PEG-rhG-CSF+G-CSF group were better than those in the G-CSF group, and the granulocyte recovery time ([10.25±0.78]d vs [13.68±0.42]d, P=0.001) and platelet recovery time ([10.42±0.41]d vs [13.15±0.41]d, P=0.007) in the PEG-rhG-CSF+G-CSF group were better than those in the chemotherapy+G-CSF group. There was no significant difference in acquisition success rate among the three groups(P>0.05). All patients successfully achieved hematopoietic reconstruction after transplantation, and no transplant-related death occurred.Conclusion Compared with chemotherapy+G-CSF and G-CSF mobilization alone, the long- and short-acting G-CSF combined mobilization regimen has higher CD34+cell collection number and good rate of collection, and significantly shortens the time of hematopoietic reconstruction. This mobilization regimen can be a good option for autologous peripheral blood mobilization in patients with malignant hematological diseases. -
-
表 1 71例患者的基本临床资料
例(%) 项目 PEG-rhG-CSF+G-CSF组 单用G-CSF组 化疗+G-CSF组 P 例数 12 25 34 性别 0.071 男 4(33.3) 16(64.0) 24(70.6) 女 8(66.7) 9(36.0) 10(29.4) 年龄 0.145 ≤55岁 11(91.7) 15(60.0) 23(67.6) >55岁 1(8.3) 10(40.0) 11(32.4) 疾病类型 0.215 多发性骨髓瘤 8(66.7) 9(36.0) 16(47.1) 淋巴瘤 4(33.3) 16(64.0) 18(52.9) 化疗次数 0.134 < 5次 8(66.7) 8(32.0) 14(41.2) ≥5次 4(33.3) 17(68.0) 20(58.8) 诊疗周期 0.419 < 6个月 7(58.3) 9(36.0) 16(47.1) ≥6个月 5(41.7) 16(64.0) 18(52.9) 
下载: 导出CSV
表 2 各因素对造血干细胞的影响
项目 例数 采集MNC/(×108/kg) P 采集CD34+细胞数/(×106/kg) P 采集成功率/例(%) P 采集优良率/例(%) P 性别 0.194 0.559 0.176 0.655 男 44 8.03±0.59 7.66±1.33 38(86.4) 27(61.4) 女 27 9.25±0.73 9.02±1.99 26(96.3) 18(66.7) 年龄 0.844 0.203 0.016 0.119 ≤55岁 49 8.43±0.53 9.13±1.51 47(95.9) 34(69.4) >55岁 22 8.63±0.89 6.05±1.18 17(77.3) 11(50.0) 疾病类型 0.613 0.868 0.074 0.307 多发性骨髓瘤 33 8.74±0.63 8.38±1.69 32(97.0) 23(69.7) 淋巴瘤 38 8.28±0.65 8.00±1.50 32(84.2) 22(57.9) 化疗次数 0.537 0.003 0.018 0.139 < 5次 30 8.82±0.67 11.67±2.38 30(100.0) 22(73.3) ≥5次 41 8.25±0.60 5.63±0.61 34(82.9) 23(56.1) 诊疗周期 0.628 0.307 0.087 0.068 < 6个月 32 8.74±0.65 9.44±2.28 31(96.9) 24(75.0) ≥6个月 39 8.29±0.62 7.14±0.79 33(84.6) 21(53.8)
下载: 导出CSV
表 3 不同动员方案对自体外周血造血干细胞移植后造血重建的影响
X±S 动员方案 例数 中性粒细胞 < 0.5×109/L
持续时间/d血小板 < 20×109/L
持续时间/d中性粒细胞≥ 0.5×109/L
开始时间/d血小板≥ 20×109/L
开始时间/dPEG-rhG-CSF+G-CSF组 12 7.25±0.56 5.33±0.45 10.25±0.78 10.42±0.41 单用G-CSF组 25 9.52±0.66 7.44±0.64 12.56±0.69 12.68±0.70 化疗+G-CSF组 34 9.91±0.44 8.12±0.39 13.68±0.42 13.15±0.41 P 0.019 0.007 0.003 0.014
下载: 导出CSV
-
[1] Ikeda T, Mori K, Kawamura K, et al. Comparison between autologous and allogeneic stem cell transplantation as salvage therapy for multiple myeloma relapsing/progressing after autologous stem cell transplantation[J]. Hematol Oncol, 2019, 37(5): 586-594. doi: 10.1002/hon.2688
[2] Snowden JA, Sánchez-Ortega I, Corbacioglu S, et al. Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe[J]. Bone Marrow Transplant, 2022, 57(8): 1217-1239. doi: 10.1038/s41409-022-01691-w
[3] 郭巧花, 秦小琪, 王世芳, 等. 多发性骨髓瘤患者自体造血干细胞移植后免疫球蛋白重建及生存分析[J]. 临床血液学杂志, 2022, 35(3): 195-200, 206. doi: 10.13201/j.issn.1004-2806.2022.03.009
[4] Nishimura KK, Barlogie B, van Rhee F, et al. Long-term outcomes after autologous stem cell transplantation for multiple myeloma[J]. Blood Adv, 2020, 4(2): 422-431. doi: 10.1182/bloodadvances.2019000524
[5] Oliver-Caldes A, Soler-Perromat JC, Lozano E, et al. Long-Term Responders After Autologous Stem Cell Transplantation in Multiple Myeloma[J]. Front Oncol, 2022, 12: 936993. doi: 10.3389/fonc.2022.936993
[6] 胡琴, 陈刚, 徐建丽, 等. 美法仑联合自体外周血造血干细胞移植治疗多发性骨髓瘤: 无进展生存单中心临床分析[J]. 临床血液学杂志, 2023, 36(9): 665-671. https://lcxy.whuhzzs.com/article/doi/10.13201/j.issn.1004-2806.2023.09.011
[7] 中华医学会血液学分会, 中国临床肿瘤学会(CSCO)抗淋巴瘤联盟. 淋巴瘤自体造血干细胞动员和采集中国专家共识(2020年版)[J]. 中华血液学杂志, 2020, 41(12): 979-983. doi: 10.3760/cma.j.issn.0253-2727.2020.12.002
[8] Wei X, Wei Y. Stem cell mobilization in multiple myeloma: challenges, strategies, and current developments[J]. Ann Hematol, 2023, 102(5): 995-1009. doi: 10.1007/s00277-023-05170-0
[9] Ding X, Huang W, Peng Y, et al. Pegfilgrastim improves the outcomes of mobilization and engraftment in autologous hematopoietic stem cell transplantation for the treatment of multiple myeloma[J]. Ann Hematol, 2020, 99(6): 1331-1339. doi: 10.1007/s00277-019-03800-0
[10] Danylesko I, Sareli R, Varda-Bloom N, et al. Long-acting granulocyte colony-stimulating factor pegfilgrastim(lipegfilgrastim)for stem cell mobilization in multiple myeloma patients undergoing autologous stem cell transplantation[J]. Int J Hematol, 2021, 114(3): 363-372. doi: 10.1007/s12185-021-03177-9
[11] 王婷, 冯茹, 李江涛, 等. 聚乙二醇重组人粒细胞集落刺激因子在自体造血干细胞动员中的应用[J]. 中华血液学杂志, 2021, 42(1): 70-73. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZL201713013.htm
[12] Ma H, Zhu X, Gao L, et al. Effect of PEG-rhG-CSF on primary prevention of neutropenia after simultaneous radiotherapy and chemotherapy[J]. Minerva Surg, 2023, 78(3): 309-310.
[13] Keklik M, Karakus E, Kaynar L, et al. Low-dose cyclophosphamide and granulocyte colony-stimulating factor are sufficient for peripheral blood stem cell mobilization in patients with multiple myeloma[J]. Transfus Apher Sci, 2020, 59(5): 102844. doi: 10.1016/j.transci.2020.102844
[14] Moreb JS, Byrne M, Shugarman I, et al. Poor peripheral blood stem cell mobilization affects long-term outcomes in multiple myeloma patients undergoing autologous stem cell transplantation[J]. J Clin Apher, 2018, 33(1): 29-37. doi: 10.1002/jca.21556
[15] Chang HH, Liou YS, Sun DS. Hematopoietic stem cell mobilization[J]. Tzu Chi Med J, 2022, 34(3): 270-275. doi: 10.4103/tcmj.tcmj_98_21
[16] Hsu TL, Tsai CK, Liu CY, et al. Risk Factors and Outcomes of Stem Cell Mobilization Failure in Multiple Myeloma Patients[J]. Transfus Med Hemother, 2023, 50(1): 39-50. doi: 10.1159/000525565
[17] Liu XT, Zhao YX, Jia GW, et al. Pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor in children with acute leukaemia[J]. Br J Clin Pharmacol, 2021, 87(8): 3292-3300. doi: 10.1111/bcp.14750
[18] Hu C, Ji B, Hu X, et al. Pharmacokinetics and Pharmacodynamics of Two Formulations of Pegylated Recombinant Human Granulocyte Colony-Stimulating Factor in Healthy Chinese Subjects: An Open-Label, Randomized, Parallel-Design Bioavailability Study[J]. Clin Pharmacol Drug Dev, 2021, 10(3): 291-298. doi: 10.1002/cpdd.819
[19] Jung EH, Byun JM, Shin DY, et al. Mobilization of hematopoietic stem cells with lenograstim in multiple myeloma patients: Prospective multicenter observational study(KMM122)[J]. Cancer Med, 2023, 12(8): 9186-9193. doi: 10.1002/cam4.5657
[20] Wen J, Zhou Q, Shi L, et al. A novel PEGylated form of granulocyte colony-stimulating factor, mecapegfilgrastim, for peripheral blood stem cell mobilization in patients with hematologic malignancies[J]. BMC Cancer, 2023, 23(1): 694. doi: 10.1186/s12885-023-11197-3
[21] Mehta HM, Corey SJ. G-CSF, the guardian of granulopoiesis[J]. Semin Immunol, 2021, 54: 101515. doi: 10.1016/j.smim.2021.101515
[22] Volkmann J, Schmitz J, Nordlohne J, et al. Kidney injury enhances renal G-CSF expression and modulates granulopoiesis and human neutrophil CD177 in vivo[J]. Clin Exp Immunol, 2020, 199(1): 97-108.
[23] Cordoba R, Eyre TA, Klepin HD, et al. A comprehensive approach to therapy of haematological malignancies in older patients[J]. Lancet Haematol, 2021, 8(11): e840-e852. doi: 10.1016/S2352-3026(21)00241-6
[24] Goker H, Ciftciler R, Demiroglu H, et al. Predictive factors for stem cell mobilization failure in multiple myeloma patients: A single center experience[J]. Transfus Apher Sci, 2020, 59(1): 102595. doi: 10.1016/j.transci.2019.06.023
[25] Arora S, Majhail NS, Liu H. Hematopoietic Progenitor Cell Mobilization for Autologous Stem Cell Transplantation in Multiple Myeloma in Contemporary Era[J]. Clin Lymphoma Myeloma Leuk, 2019, 19(4): 200-205. doi: 10.1016/j.clml.2018.12.010
[26] 苏永锋, 王艺志, 宁红梅, 等. 淋巴瘤与多发性骨髓瘤患者自体外周血造血干细胞动员影响因素分析[J]. 中国实验血液学杂志, 2021, 29(6): 1945-1949. https://www.cnki.com.cn/Article/CJFDTOTAL-XYSY202106046.htm
-
图(1)
表(3)
计量
- 文章访问数: 520
- PDF下载数: 157
- 施引文献: 0