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自体外周血造血干细胞移植(autologous peripheral blood stem cell transplantation,APBSCT)目前已广泛应用于多种恶性血液病病人且取得了较好疗效,部分病人无病生存时间及总体生存时间明显延长[1]。与传统的异基因移植相比,由于APBSCT无移植物抗宿主反应(GVHD)且无供者来源影响,目前对其年龄要求相对放宽,国外曾报道有80岁高龄病人移植成功案例[2]。然而,由于经济、药物、观念等因素影响,国内APBSCT开展的比例及成功率均落后于发达国家。
采集足量的外周血造血干细胞是APBSCT成功的关键[3]。影响外周血造血干细胞采集的因素很多,如年龄、疾病状态、移植前化疗疗程数、是否使用特殊药物,采集当日CD34+细胞及白细胞计数等[4]。目前自体外周血干细胞动员方案主要有3种:G-CSF直接动员、常规化疗(如R-CHOP、PAD、IA等方案)后动员及大剂量CTX或VP-16方案动员。然而,不同动员方案的效果各文献报告并不一致[5]。本研究回顾性分析了2018年8月至2020年5月我院及安徽医科大学第一附属医院血液科收治的恶性血液病病人资料,对比采用G-CSF、大剂量VP-16+G-CSF及CTX+G-CSF方案行外周血干细胞动员的效果及影响因素。现作报道。
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共采集31例59次,获得单个核细胞(5.7±1.6)×108/kg,CD34+细胞(2.1±0.7)×106/kg。采集成功所需采集次数方面,其中7例为1次、13例为2次。7例3次动员后仍失败,采集失败者包括NHL3例,MM4例。优质动员采集5例。
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G-CSF组动员至采集中位时间4 d,但CD34+细胞产量低于其他2组(P < 0.05),VP-16组与CTX组采集CD34+细胞数量差异无统计学意义(P > 0.05),VP-16组与CTX组动员至采集中位天数均为12 d。CTX组采集时血小板水平低于VP-16组(P < 0.05)(见表 1)。VP-16组出现化疗后粒细胞缺乏并发热(> 38 ℃)5例,CTX组出现3例。
动员方案 n CD34+细胞数/
(106/kg)动员采集中位
时间/d发热 血小板最低值/
(×109/L)G-CSF 9 1.60±0.39 4 0(0.00) — VP-16 15 2.38±0.55* 12 5(33.33) 32.3±10.4 CTX 7 2.30±0.43* 12 3(42.86) 17.5±7.1 F — 2.46 4.64# 1.66△ P — > 0.05 > 0.05 < 0.05 MS组内 — 0.525 — — — 与G-CSF组比较*P < 0.05;#示χ2值 表 1 3种动员方案优劣势比较(x ±s)
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采集的CD34+细胞数男性病人高于女性,≤55岁病人高于 > 55岁,≤8个化疗疗程病人高于 > 8个化疗疗程病人,优于PR病人高于PR病人,差异均有统计学意义(P < 0.05);除2例白血病病例外,淋巴瘤病人CD34+细胞数与多发性骨髓瘤病人差异无统计学意义(P > 0.05)(见表 2)。
一般资料 n CD34+细胞数/(×106/kg) t P 性别 男 17 2.25±0.38 2.61 < 0.05 女 14 1.81±0.51 疗程/个 > 8 15 1.61±0.51 4.95 < 0.05 ≤8 16 2.10±0.64 疾病缓解程度 PR 9 1.60±0.54 3.57 < 0.05 优于PR 22 2.10±0.63 年龄/岁 > 55 11 1.52±0.58 3.39 < 0.05 ≤55 20 2.18±0.62 病种 淋巴瘤 15 2.19±0.66 2.18 > 0.05 骨髓瘤 12 2.27±0.63 表 2 不同因素下干细胞采集数量的比较(x ±s)
恶性血液病病人自体外周血造血干细胞动员采集影响因素分析
Analysis of the influencing factors of mobilization and collection of autologous hematopathy in patient with malignant blood disease
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摘要:
目的探讨不同动员方案以及年龄、化疗疗程、疾病缓解状态等因素对自体外周血干细胞采集动员效果的影响。 方法回顾性分析31例急性白血病、恶性淋巴瘤及多发性骨髓病人病历资料。分别行直接G-CSF动员方案(G-CSF组)及大剂量VP-16+G-CSF动员方案(VP-16组)、CTX+G-CSF动员方案(CTX组),对比不同动员方案中采集细胞数量、血液学指标变化、不良反应等,分析年龄、性别、疾病状态、化疗疗程、治疗至动员时间等因素分析对干细胞采集影响。 结果31人共采集59次,获得单个核细胞(5.7±1.6)×108/kg,CD34+细胞(2.1±0.7)×106/kg。G-CSF组动员至采集中位时间4 d,但CD34+细胞产量低于其他2组(P < 0.05),VP-16组与CTX组采集CD34+细胞数量差异无统计学意义(P>0.05),VP-16组与CTX组动员至采集中位时间均为12 d。CTX组采集时血小板水平低于VP-16组(P < 0.05)。VP-16组出现化疗后粒细胞缺乏并发热(>38℃)5例,CTX组出现3例。采集的CD34+细胞数男性病人高于女性,≤55岁病人高于>55岁,≤8个化疗疗程病人高于>8个化疗疗程病人,优于部分缓解病人高于部分缓解病人,差异均有统计学意义(P < 0.05)。 结论化疗联合G-CSF方案可以动员出更多CD34+细胞数,大剂量VP-16+G-CSF动员方案采集时血小板水平更高,采集安全性更有保障。男性、年龄≤55岁、化疗疗程≤8个疗程时采集成功率更高。 Abstract:ObjectiveTo explore the effects of various mobilization schemes, age, chemotherapy cycle, disease state and other factors on the autologous peripheral blood stem cell mobilization and collection. MethodsThe clinical data of 31 patients with acute leukemia(AL), Non-Hodgkin's lymphoma(NHL) and multiple myeloma(MM) were retrospectively analyzed.The patients with Granulocyte Colony-Stimulating Factor(G-CSF) mobilization scheme, large dose VP-16(Etoposide) combined with G-CSF mobilization scheme and Cyclophosphamide(CTX) combined with G-CSF mobilization scheme were divdied into the the G-CSF group, VP-16 group and CTX group, respectively.The number of cells, changes of hematological indexes and adverse reactions among three groups were compared.The effects of age, gender, disease status, chemotherapy cycle, treatment to mobilization time on stem cell collection were analyzed. ResultsA total of 59 times were collected from 31 people, and the (5.7±1.6)×108/kg mononuclear cells and (2.1±0.7)×106/kg CD34+ cells were obtained.The number of median day from mobilizating to collecting in G-CSF group was 4 days, but the CD34+ cell production in G-CSF group was lower than that in other two groups(P < 0.05).There was no statistical significance in the number of CD34+ cells between the VP-16 group and CTX group(P>0.05), and the number of median day from mobilizating to collecting in VP-16 group and CTX group were 12 days.The platelet level in CTX group was lower than that in VP-16 group(P < 0.05).Five cases with ranulocytopenia complicaed with fever(>38 ℃) in VP-17 group were found after chemotherapy, while 3 patients in the CTX group were identified.The number of CD34+ cells collection in male patients was higher than that in female patients, which in patients with ≤55 years old was higher than that in patients with >55 years old, which in patients with ≤8 chemotherapy courses was higher than that in patients with >8 chemotherapy courses, and which in CR patients was better than that in PR patients(P < 0.05). ConclusionsChemotherapy combined with G-CSF can mobilize more CD34+ cells, and the platelet level in the high-dose VP-16 + G-CSF Mobilization scheme is higher, and the safety of collection is more guaranteed.The success rates in male, age ≤55 years old and course of chemotherapy ≤8 courses patients are higher. -
表 1 3种动员方案优劣势比较(x ±s)
动员方案 n CD34+细胞数/
(106/kg)动员采集中位
时间/d发热 血小板最低值/
(×109/L)G-CSF 9 1.60±0.39 4 0(0.00) — VP-16 15 2.38±0.55* 12 5(33.33) 32.3±10.4 CTX 7 2.30±0.43* 12 3(42.86) 17.5±7.1 F — 2.46 4.64# 1.66△ P — > 0.05 > 0.05 < 0.05 MS组内 — 0.525 — — — 与G-CSF组比较*P < 0.05;#示χ2值 表 2 不同因素下干细胞采集数量的比较(x ±s)
一般资料 n CD34+细胞数/(×106/kg) t P 性别 男 17 2.25±0.38 2.61 < 0.05 女 14 1.81±0.51 疗程/个 > 8 15 1.61±0.51 4.95 < 0.05 ≤8 16 2.10±0.64 疾病缓解程度 PR 9 1.60±0.54 3.57 < 0.05 优于PR 22 2.10±0.63 年龄/岁 > 55 11 1.52±0.58 3.39 < 0.05 ≤55 20 2.18±0.62 病种 淋巴瘤 15 2.19±0.66 2.18 > 0.05 骨髓瘤 12 2.27±0.63 -
[1] MOREB JS, BYRNE M, ZOU F, 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. doi: 10.1002/jca.21556 [2] SHAH H, KIM S, SINGH P, et al.Clinical outcomes of multiple myeloma patients who undergo autologous hematopoietic stem cell transplant with G-CSF or G-CSF and plerixafor mobilized grafts [J].Am J Hematol, 2020, 95(2):198. doi: 10.1002/ajh.25672 [3] FIGUEIREDO A, KASSIS R, ALBACKER R, et al.The impact of multiple myeloma induction therapy on hematopoietic stem cell mobilization and collection:25-year experience [J].Hematol Transfus Cell Ther, 2019, 41 (4):285. doi: 10.1016/j.htct.2019.03.005 [4] GIRALT S, COSTA L, SCHRIBER J, et al.Optimizing autologous stem cell mobilization strategies to improve patient outcomes:consensus guidelines and recommendations[J].Biol Blood Marrow Transplant, 2014, 20(3):295. doi: 10.1016/j.bbmt.2013.10.013 [5] KIM SS, RENTERIA AS, STEINBRERG A, et al.Pharmacoeconomic impact of up-front use of plerixafor for autologous stem cell mobilization in patients with multiple myeloma[J].Cytotherapy, 2014, 16(11):1584. doi: 10.1016/j.jcyt.2014.05.003 [6] GIRALT S, COSTA L, SCHRIBER J, et al.Optimizing autologous stem cell mobilization strategies to improve patient outcomes:consensus guidelines and recommendations[J].Biol Blood Marrow Transplant, 2014, 20(3):295. doi: 10.1016/j.bbmt.2013.10.013 [7] SAHIN U, DEMIRER T.Current strategies for the management of autologous peripheral blood stem cell mobilization failures in patients with multiple myeloma[J].J Clin Apher, 2018, 33(3):357. doi: 10.1002/jca.21591 [8] ABDALLAH N, KIM S, AYASH L, et al.Does use of biosimilar G-CSF change plerixafor utilization during stem cell mobilization for autologous stem cell transplant?[J].Bone Marrow Transplant, 2020, 55(8):1655. doi: 10.1038/s41409-019-0744-5 [9] 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 [10] LAGRESLE PEYROU C, LEFRERE F, MAGRIN E, et al.Plerixafor enables safe, rapid, efficient mobilization of hematopoietic stem cells in sickle cell disease patients after exchange transfusion[J].Haematologica, 2018, 103(5):778. doi: 10.3324/haematol.2017.184788 [11] SHAH EE, YOUNG RP, WONG SW, et al.Impact of plerixafor use at different peripheral blood CD34 thresholds on autologous stem cell collection in patients with multiple myeloma[J].Biol Blood Marrow Transplant, 2020, 26(5):876. doi: 10.1016/j.bbmt.2019.11.024 [12] GUTIERRES AGUIRRE CH, ALVARADO-NAVARRO DM, PALOMARES LEAL A, et al.Reduced-dose plerixafor as a mobilization strategy in autologous hematopoietic cell transplantation:a proof of concept study[J].Transfusion, 2019, 59(12):3721. doi: 10.1111/trf.15547 [13] KUMAR SK, BERDEJA JG, NIESVIZKY R, et al.Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma:an open-label phase 1/2 study[J].Lancet Oncol, 2014, 15(13):1503. doi: 10.1016/S1470-2045(14)71125-8 [14] BUNEO JL, ALEGRE A, LOPEA VILLAR O, et al.Agreements and uncertainties in autologous haematopoietic stem cell mobilization and collection.A Spanish consensus document[J].Bone Marrow Transplant, 2020, 55(4):811. doi: 10.1038/s41409-019-0716-9