Peripheral Blood Stem Cell Transplantation

外周血干细胞移植
  • 文章类型: Journal Article
    Objective: The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) . Methods: Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1∶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed. Results: ①Collection results: the ETO and CTX groups [2 (1-3) d vs 2 (1-5) d; P<0.001] and CD34(+) cells [7.62×10(6) (2.26×10(6)-37.20×10(6)) /kg vs 2.73×10(6) (0.53×10(6)-9.85×10(6)) /kg; P<0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) (P<0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; P<0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. ②Adverse reactions: granular deficiency with fever (21.5%[14/65] vs. 10.7%[6/56]; P=0.110), requiring platelet transfusion [10.7% (7/65) vs 1.8% (1/56) ; P=0.047]. ③Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34(+) cells infused in the two groups was 4.62×10(6) (2.14×10(6)-19.89×10(6)) /kg versus 2.62×10(6) (1.12×10(6)-5.31×10(6)) /kg (P<0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d (P=0.049), and platelet implantation time was 11 (0-19) d vs. 12 (0-34) d (P=0.035). One case in the CTX group experienced delayed platelet implantation. Conclusion: The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34(+) cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.
    目的: 比较依托泊苷(ETO)联合G-CSF与环磷酰胺(CTX)联合G-CSF在多发性骨髓瘤(MM)患者中进行自体外周血造血干细胞动员的效果及安全性。 方法: 纳入2020年1月1日至2023年7月31在首都医科大学附属北京朝阳医院血液科接受自体外周血造血干细胞动员、采集的MM患者,利用倾向性评分按照1∶1匹配比例筛选出134例患者,ETO联合G-CSF动员方案(ETO组)、CTX联合G-CSF动员方案(CTX组)各67例,对其临床资料进行回顾性分析。 结果: ①ETO组、CTX组采集天数分别为2(1~3)d、2(1~5)d(P<0.001),CD34(+)细胞采集量分别为7.62(2.26~37.20)×10(6)/kg、2.73(0.53~9.85)×10(6)/kg(P<0.001),采集成功率分别为100.0%(67/67)、76.1%(51/67)(P<0.001)、采集优良率分别为82.1%(55/67)、20.9%(14/67)(P<0.001)。ETO组有2例患者在采集1 d后进行方案转换,CTX组有11例患者在采集1~2 d后进行方案转换。②ETO组、CTX组粒缺伴发热发生率分别为21.5%(14/65)、10.7%(6/56)(P=0.110),血小板输注患者占比分别为10.7%(7/65)、1.8%(1/56)(P=0.047)。③至随访截止,ETO组63例、CTX组54例患者接受了自体造血干细胞移植,中位CD34(+)细胞回输量分别为4.62(2.14~19.89)×10(6)/kg、2.62(1.12~5.31)×10(6)/kg(P<0.001),中性粒细胞植入时间分别为11(9~14)d、11(10~14)d(P=0.049),血小板植入时间分别为11(0~19)d、12(0~34)d(P=0.035)。CTX组有1例患者发生血小板延迟植入。 结论: 依托泊苷联合G-CSF的动员方案可能有较多的患者需要输注血小板,但采集天数缩短,采集成功率、优良率及CD34(+)细胞采集量较高,移植后中性粒细胞和血小板植入较快。.
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  • 文章类型: Journal Article
    本报告提供一例病例,涉及一名年龄>65岁的女性,3年前被诊断患有边缘区淋巴瘤。患者因腹股沟淋巴结肿大住院,病理检查显示淋巴瘤已转化为弥漫性大B细胞淋巴瘤。在两个周期的本妥昔单抗维多汀联合利妥昔单抗后,环磷酰胺,阿霉素,和泼尼松(BV-R-CHP)化疗,患者达到完全缓解。随后进行自体造血干细胞移植和来那度胺维持治疗。在最后一次随访中,患者持续缓解24个月.这个案例研究表明,联合使用BV和R-CHP可以导致快速缓解,后可进行自体造血干细胞移植和来那度胺维持治疗。这种治疗方法显示出作为患有转化淋巴瘤的老年个体的可行选择的潜力。
    This report presents a case involving a woman aged >65 years who had been diagnosed with marginal zone lymphoma 3 years prior. The patient was hospitalized with enlarged inguinal lymph nodes, and pathological examination revealed that the lymphoma had transformed into diffuse large B-cell lymphoma. After two cycles of brentuximab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (BV-R-CHP) chemotherapy, the patient achieved complete remission. This treatment was followed by autologous hematopoietic stem cell transplantation and lenalidomide maintenance therapy. At the last follow-up, the patient had been in continuous remission for 24 months. This case study suggests that the utilization of BV and R-CHP in conjunction can result in rapid remission, and it can be followed by autologous hematopoietic stem cell transplantation and maintenance therapy with lenalidomide. This treatment approach exhibits potential as a viable option for older individuals with transformed lymphoma.
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  • 文章类型: Journal Article
    目的:多发性骨髓瘤(MM)是自体造血干细胞移植的主要适应症。这项研究的目的是确定新疗法时代MM患者动员失败的发生率,并表征与动员不良(PM)相关的危险因素。
    方法:我们对211例MM患者进行了回顾性研究,这些患者在我们的单中心首次接受了外周血干细胞(PBSC)动员。收集了以下数据:年龄,性别,临床分期,疾病状态,全血细胞计数,诱导方案,外周血CD34+细胞计数(PB),和PBSC集合。
    结果:除了常规药物,22例(10.4%)患者接受了含有达雷妥单抗的诱导,33例(15.6%)患者使用plerixafor动员不良(单采前PBCD34细胞<20/μL)。收集失败发生在24(11.4%)患者中,并与低白细胞(WBC)相关,动员前≥3个周期的来那度胺治疗,稳态动员和plerixafor的nouse与动员失败有关。基于Daratumumab的诱导治疗≥2个疗程,动员前白蛋白>41g/L,和稳态动员是来那度胺治疗<3个疗程患者亚组PM的危险因素。此外,基线时乙型肝炎病毒感染,在化学动员患者的子集中,地中海贫血和可测量的残留疾病阳性被认为是PM的预测因素。
    结论:除了一些公认的风险因素,基线白细胞计数和动员前达雷妥单抗暴露≥2个疗程显示为动员失败的预测因素,为抢先使用plerixafor提供咨询。
    OBJECTIVE: Multiple myeloma (MM) is the leading indication of autologous hematopoietic stem cell transplantation. The aim of this study was to determine the incidence of mobilization failure and characterize the risk factors associated with poor mobilization (PM) of MM patients in novel therapies era.
    METHODS: We conducted a retrospective study of 211 MM patients who received their first peripheral blood stem cells (PBSC) mobilization at our single center. The following data were collected: age, gender, clinical stage, disease status, complete blood cell count, induction regimen, CD34+ cell count in peripheral blood (PB), and PBSC collections.
    RESULTS: In addition to conventional drugs, 22 (10.4%) patients received daratumumab containing induction, and 33 (15.6%) patients used plerixafor for poor mobilization (pre-apheresis PB CD34+ cells <20/μL). Failure of collection occurred in 24 (11.4%) patients and was correlated with low white blood cell (WBC), ≥3 cycles of lenalidomide treatment before mobilization, steady-state mobilization and nouse of plerixafor are associated with mobilization failure. Daratumumab-based induction treatment ≥2 courses, albumin >41 g/L before mobilization, and steady-state mobilization were risk factors for PM in subgroups of patients treated with lenalidomide for <3 courses. In addition, Hepatitis B virus infection at baseline, thalassemia and measurable residual disease positivity were recognized as predictive factors for PM in subset of chemo-mobilization patients.
    CONCLUSIONS: In addition to some well-recognized risk factors, baseline WBC count and daratumumab exposure ≥2 courses before mobilization were revealed as the predictive factors of mobilization failure, providing consultation for preemptive use of plerixafor.
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  • 文章类型: Case Reports
    聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)已被引入用于动员外周血干细胞(PBSC)。然而,没有健康供体急性肺损伤(ALI)的报道,和潜在的机制仍然知之甚少。我们首次报道了一例健康中国供体中PEG-rhG-CSF引起的ALI,以咯血为特征,低氧血症,和零散的阴影。最终,激素给药,计划的PBSC收集,白细胞清创术,和计划的PBSC收集导致对捐赠者的ALI的主动控制。捐献者的症状有所改善,没有任何不良反应,并且PBSC收集没有发生任何事件。随着时间的推移,肺部病变逐渐吸收,最终恢复正常。PEG-rhG-CSF可能通过涉及中性粒细胞聚集的机制促进健康供体的ALI,附着力,以及肺部炎症介质的释放。该病例报告检查了临床表现,治疗,PEG-rhG-CSF动员PBSCs诱导肺损伤的机制。
    Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) has been introduced for the mobilization of peripheral blood stem cells (PBSCs). However, no cases of acute lung injury (ALI) in healthy donors have been reported, and the underlying mechanisms remain poorly understood. We first reported a case of ALI caused by PEG-rhG-CSF in a healthy Chinese donor, characterized by hemoptysis, hypoxemia, and patchy shadows. Ultimately, hormone administration, planned PBSC collection, leukocyte debridement, and planned PBSC collection resulted in active control of the donor\'s ALI. The donor\'s symptoms improved without any adverse effects, and the PBSC collection proceeded without incident. Over time, the lung lesion was gradually absorbed and eventually returned to normal. PEG-rhG-CSF may contribute to ALI in healthy donors via mechanisms involving neutrophil aggregation, adhesion, and the release of inflammatory mediators in the lung. This case report examines the clinical manifestations, treatment, and mechanism of lung injury induced by PEG-rhG-CSF-mobilized PBSCs.
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  • 文章类型: English Abstract
    OBJECTIVE: To analyze the effect of recombinant human thrombopoietin (rhTPO) on platelet (PLT) reconstitution after autologous peripheral blood stem cell transplantation (APBSCT) in patients with multiple myeloma (MM).
    METHODS: The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed. According to whether rhTPO was used during APBSCT, the patients were divided into rhTPO group (80 cases) and control group (67 cases). The time of PLT engraftment, blood product infusion requirements, the proportion of patients with PLT recovery to≥50×109/L and≥100×109/L at +14 days and +100 days after transplantation, and adverse reactions including the incidence of bleeding were compared between the two groups.
    RESULTS: There were no significant differences between the two groups in sex, age, M protein type, PLT count at the initial diagnosis, median duration of induction therapy before APBSCT, and number of CD34+ cells reinfused (all P >0.05). The median time of PLT engraftment in the rhTPO group was 10 (6-14) days, which was shorter than 11 (8-23) days in the control group (P < 0.001). The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U, which was less than 20 (0-80)U in the control group (P =0.001). At +14 days after transplantation, the proportions of patients with PLT≥50×109/L in the rhTPO group and the control group were 66.3% and 52.2%, while the proportions of patients with PLT≥100×109/L were 23.8% and 11.9%, respectively, with no significant differences (all P >0.05). At +100 days after transplantation, the proportion of patients with PLT≥50×109/L in rhTPO group and control group was 96.3% and 89.6%, respectively (P >0.05), but the proportion of patients with PLT≥100×109/L in rhTPO group was higher than that in control group (75.0% vs 55.2%, P =0.012). There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups. In rhTPO group, the rhTPO administration was well tolerated, and the incidences of abnormal liver and kidney function and infection were similar to those in the control group.
    CONCLUSIONS: When MM patients undergo first-line APBSCT, subcutaneous injection of rhTPO can shorten the time of platelet engraftment, reduce the transfusion volume of blood products, and be well tolerated, moreover, more patients have achieve a high level of PLT recovery after transplantation, which is very important for ensuring the safety of APBSCT and maintenance therapy.
    UNASSIGNED: 重组人血小板生成素对多发性骨髓瘤患者自体外周血造血干细胞移植术后血小板重建影响的研究.
    UNASSIGNED: 分析重组人血小板生成素(rhTPO)对多发性骨髓瘤(MM)患者自体外周血造血干细胞移植术 (APBSCT)后血小板(PLT)重建的影响。.
    UNASSIGNED: 回顾性分析在苏州大学附属第一医院一线行APBSCT治疗的147例MM患者的临床资料,根据APBSCT期间是否使用rhTPO分为rhTPO组80例和对照组67例,比较两组患者在PLT植入时间、血制品输注需求量、移植后+14和+100 d PLT恢复至≥50×109/L和≥100×109/L的患者比例以及出血发生率等方面的差异。.
    UNASSIGNED: 两组患者在性别、年龄、M蛋白类型、初诊时PLT数、APBSCT前诱导治疗中位疗程数、回输的CD34+细胞数方面均无统计学差异(均P >0.05)。rhTPO组患者PLT植入中位时间为10(6-14)d,较对照组11(8-23)d显著缩短(P < 0.001)。rhTPO组患者在APBSCT期间的中位PLT输注需求量为15(0-50)U,较对照组20(0-80)U更少(P =0.001)。移植后+14 d时rhTPO组和对照组PLT≥50×109/L的患者比例分别为66.3% 和52.2%,PLT≥100×109/L的患者比例分别为23.8%和11.9%,比较差异均无统计学意义(P >0.05)。在移植后+100 d时,rhTPO组和对照组PLT≥50×109/L的患者比例分别为96.3%和89.6%(P >0.05),但rhTPO组PLT≥ 100×109/L的患者比例高于对照组(75.0% vs 55.2%,P =0.012)。两组患者在PLT水平低下期间不同部位出血事件的总体发生率无差异,且rhTPO组治疗耐受性良好,肝肾功能异常和感染的发生概率与对照组类似。.
    UNASSIGNED: MM患者在一线行APBSCT时,皮下注射rhTPO药物可以缩短PLT植入时间,减少血制品的需求量,耐受性良好,且在移植后有更多患者达到了PLT高水平的恢复,这对保证APBSCT和MM患者维持治疗期间的安全具有重要意义。.
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  • 文章类型: English Abstract
    Objectives: To assess the efficacy of cord blood-assisted haploid peripheral blood stem cell transplantation (haplo-cord-PBSCT) versus unrelated donor peripheral blood stem cell transplantation (UD-PBSCT) in the treatment of malignant hematological diseases. Methods: A retrospective analysis was performed on one hundred and four patients with malignant hematological diseases who underwent haplo-cord-PBSCT and fifty-two patients who underwent UD-PBSCT at Xiangya Hospital of Central South University between January 2016 and December 2021. Results: ①The median implantation time for neutrophils in the haplo-cord-PBSCT and UD-PBSCT groups was 13 (9-22) days and 13 (10-24) days, respectively (P=0.834), whereas the median implantation time for platelets was 15 (7-103) days and 14 (8-38) days, respectively (P=0.816). The cumulative implantation rate of neutrophils at 30 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group was 100% (P=0.314), and the cumulative platelet implantation rate at 100 days after transplantation was 95.2% (95% CI 88.3% - 98.1% ) and 100% (P=0.927), respectively. 30 days after transplantation, both groups of patients achieved complete donor chimerism, and no umbilical cord blood stem cells were implanted. ②The cumulative incidence rates of grade Ⅱ-Ⅳ acute GVHD within 100 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group were 29.1% (95% CI 20.1% -38.1% ) and 28.8% (95% CI 17.2% -41.6% (P=0.965), respectively. The cumulative incidence rates of grade Ⅲ/Ⅳ acute GVHD were 7.8% (95% CI 3.6% -14.0% ) and 9.6% (95% CI 3.5% -19.5% ) (P=0.725). The cumulative incidence rates of 2-year chronic GVHD in the haplo-cord-PBSCT group and the UD-PBSCT group were 45.3% (95% CI 36.1% -56.1% ) and 35.1% (95% CI 21.6% -44.1% ), respectively (P=0.237). The cumulative incidence rates of severe chronic GVHD at 2 years after transplantation were 13.6% (95% CI 7.6% -21.3% ) and 12.9% (95% CI 5.1% -24.3% ), respectively (P=0.840). ③The 2-year CIR after transplantation in the haplo-cord-PBSCT group and UD-PBSCT group were 12.8% (95% CI 7.0% -20.5% ) and 10.0% (95% CI 3.6% -20.2% ), respectively (P=0.341), and the NRM were 14.7% (95% CI 8.4% -22.6% ) and 16.2% (95% CI 7.4% -28.0% ), respectively (P=0.681). ④The 2-year OS rates in the haplo-cord-PBSCT and UD-PBSCT groups after transplantation were 82.2% (95% CI 74.8% -90.3% ) and 75.5% (95% CI 64.2% -88.7% ), respectively (P=0.276). The 2-year DFS rates were 69.9% (95% CI 61.2% -79.8% ) and 73.8% (95% CI 62.4% -87.3% ), respectively (P=0.551). The 2-year rates of GVHD-free/recurrence-free survival (GRFS) were 55.3% (95% CI 44.8% -64.8% ) and 64.7% (95% CI 52.8% -79.3% ), respectively (P=0.284) . Conclusion: The findings of this study indicate that haplo-cord-PBSCT and UD-PBSCT have comparable efficacy and safety in the treatment of malignant hematological diseases and can be used as an alternative treatment options.
    目的: 比较脐带血辅助单倍体外周血干细胞移植(haplo-cord-PBSCT)与无关供者外周血干细胞移植(UD-PBSCT)治疗恶性血液病的疗效。 方法: 对中南大学湘雅医院2016年1月至2021年12月的104例接受haplo-cord-PBSCT和52例接受UD-PBSCT)的恶性血液病患者进行回顾性分析。 结果: ①haplo-cord-PBSCT和UD-PBSCT组中性粒细胞中位植入时间分别为13(9~22)d、13(10~24)d(P=0.834),血小板植入中位时间分别为15(7~103)d、14(8~38)d(P=0.816)。haplo-cord-PBSCT组和UD-PBSCT组移植后30 d中性粒细胞累积植入率均为100.0%(P=0.314),移植后100 d血小板累积植入率分别为95.2%(95%CI 88.3%~98.1%)、100.0%(P=0.927)。移植后30 d两组患者均达到完全供者嵌合状态,未发生脐带血干细胞植入。②haplo-cord-PBSCT组与UD-PBSCT组移植后100 d内Ⅱ~Ⅳ度急性GVHD的累积发生率分别为29.1%(95%CI 20.1%~38.1%)、28.8%(95%CI 17.2%~41.6%(P=0.965),Ⅲ/Ⅳ度急性GVHD的累积发生率分别为7.8%(95%CI 3.6%~14.0%)、9.6%(95%CI 3.5%~19.5%)(P=0.725)。haplo-cord-PBSCT组与UD-PBSCT组2年慢性GVHD的累积发生率分别为45.3%(95%CI 36.1%~56.1%)、35.1%(95%CI 21.6%~44.1%)(P=0.237),移植后2年重度慢性GVHD的累积发生率分别为13.6%(95%CI 7.6%~21.3%)、12.9%(95%CI 5.1%~24.3%)(P=0.840)。③haplo-cord-PBSCT组、UD-PBSCT组移植后2年CIR分别为12.8%(95%CI 7.0%~20.5%)、10.0%(95%CI 3.6%~20.2%)(P=0.341),NRM分别为14.7%(95%CI 8.4%~22.6%)、16.2%(95%CI 7.4%~28.0%)(P=0.681)。④haplo-cord-PBSCT组、UD-PBSCT组移植后2年OS率分别为82.2%(95%CI 74.8%~90.3%)、75.5%(95%CI 64.2%~88.7%)(P=0.276),2年DFS率分别为69.9%(95%CI 61.2%~79.8%)、73.8%(95%CI 62.4%~87.3%)(P=0.551),2年无GVHD无复发生存(GRFS)率分别为55.3%(95%CI 44.8%~64.8%)、64.7%(95%CI 52.8%~79.3%)(P=0.284)。 结论: haplo-cord-PBSCT与UD-PBSCT治疗恶性血液病具有相似的疗效和安全性,可作为恶性血液病的替代治疗方案。.
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  • 文章类型: Journal Article
    探讨脐带间充质干细胞(UC-MSCs)联合外周血干细胞(PBSCs)移植治疗儿童和青少年难治性或复发性重型再生障碍性贫血(R/RSAA)的新方法。对32名被诊断为R/RSAA的儿童和青少年进行了回顾性分析.根据PBSC的来源将患者分为两组:匹配的同胞供体(MSD)组和无关供体(UD)组。所有患者均未发生与UC-MSC输注相关的不良事件。中性粒细胞植入的中位时间为13天(范围:10-23天),对于血小板,15天(范围:11-28天)。在21.8和12.5%的病例中观察到I-II级急性GVHD和中度慢性GVHD,分别。在植入方面,MSD和UD组之间没有发现统计学上的显着差异,GVHD,和并发症,包括感染和出血性膀胱炎.中位随访时间为38.6个月(范围:1.4-140.8个月)。截至2021年10月31日,已有5名患者死亡,27人(84.4%)存活。MSD组和UD组的5年OS率无统计学差异(84.8±10.0vs.82.4±9.2%,p=0.674)。总之,应用UC-MSCs治疗PBSC移植中的R/RSAA,他们没有移植排斥反应,严重GVHD的低发生率,这可能是由MSC的共同输注造成的。
    To evaluate the co-transplantation efficacy of umbilical cord mesenchymal stem cells (UC-MSCs) and peripheral blood stem cells (PBSCs) as a novel approach for refractory or relapsed severe aplastic anemia (R/R SAA) in children and adolescents, thirty-two children and adolescents diagnosed with R/R SAA underwent a retrospective chart review. The patients were categorized into two groups based on the source of PBSCs: the matched sibling donor (MSD) group and the unrelated donor (UD) group. No adverse events related to UC-MSC infusion occurred in any of the patients. The median time for neutrophil engraftment was 13 days (range: 10-23 days), and for platelets, it was 15 days (range: 11-28 days). Acute GVHD of Grade I-II and moderate chronic GVHD were observed in 21.8 and 12.5% of cases, respectively. No statistically significant differences were found between the MSD and UD groups in terms of engraftment, GVHD, and complications, including infection and hemorrhagic cystitis. The median follow-up time was 38.6 months (range: 1.4-140.8 months). As of October 31, 2021, five patients had succumbed, while 27 (84.4%) survived. The 5-year OS rate showed no statistically significant difference between the MSD and UD groups (84.8 ± 10.0 vs. 82.4 ± 9.2%, p = 0.674). In conclusion, the application of UC-MSCs in the treatment of R/R SAA in PBSC transplantation is reliable and safe, they had no graft rejection, low incidence of severe GVHD which may have been contributed by the co-infusion of MSC.
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  • 文章类型: Journal Article
    在造血干细胞移植(HSCT)期间,ATG在体内消耗T细胞以改善植入并预防移植物抗宿主病(GVHD)。这里,我们比较了两种不同类型的ATGs:胸腺球蛋白和抗人T淋巴细胞免疫球蛋白(Grafalon)的临床疗效。本回顾性研究共纳入469例接受单倍体相合移植的患者。我们应用了倾向评分(PS)匹配分析,并将209例患者分配到每组。比较两组的临床结局,主要结局为总生存期(OS)。两组间OS差异无统计学意义。在HSCT后的前180天内,Grafalon与EB病毒(EBV)病毒血症的发生率较低(31.6vs.54.5%,P<0.0001)和巨细胞病毒病毒血症(CMV)病毒血症(54.5vs.67.9%,P=0.005)与胸腺球蛋白相比。接受Grafalon的患者中/重度慢性GVHD的发生率较高(26.3vs.18.2%,P=0.046)。然而,雕刻失败的发生率,II-IV级急性GVHD,复发,非复发死亡率(NRM),无GVHD无复发生存期(GRFS)在组间无显著差异.在亚组分析中,Grafalon改善了年轻年龄(<40岁)的淋巴恶性肿瘤的OS(HR,0.55;P=0.04)或具有高/非常高的疾病风险指数(HR,0.36;P=0.04)。在骨髓队列中,Grafalon降低了接受非女性男性移植移植物的患者的NRM(HR,0.17;P=0.02)。我们的结果表明,两种类型的ATG可能会不同地影响移植结果,并且可以根据患者的病情优化ATG的选择。
    During hematopoietic stem cell transplantation (HSCT), ATG depletes T cells in-vivo to improve engraftment and prevent graft-versus-host disease (GVHD). Here, we compared the clinical efficacy of two different types of ATGs: thymoglobulin and anti-human T-lymphocyte immunoglobulin (Grafalon). A total of 469 patients who received haploidentical transplantation were enrolled in this retrospective study. We applied a propensity score (PS)-matched analysis and 209 patients were assigned to each group. Clinical outcomes were compared between two groups and primary outcome was overall survival (OS). There was no significant difference in OS between two groups. Within the first 180 days after HSCT, Grafalon was associated with lower incidences of Epstein-Barr virus (EBV) viremia (31.6 vs. 54.5%, P < 0.0001) and cytomegalovirus viremia (CMV) viremia (54.5 vs. 67.9%, P = 0.005) compared to thymoglobulin. Patients receiving Grafalon had a higher rate of moderate/severe chronic GVHD (26.3 vs. 18.2%, P = 0.046). However, the incidences of engraftment failure, grade II-IV acute GVHD, relapse, non-relapse mortality (NRM), and GVHD-free relapse-free survival (GRFS) did not differ greatly between groups. In the subgroup analysis, Grafalon improved the OS of lymphoid malignancies with young ages (< 40 years old) (HR, 0.55; P = 0.04) or with a high/very high disease risk index (HR, 0.36; P = 0.04). In the myeloid cohort, Grafalon reduced NRM in the patients who received non-female for male transplantation grafts (HR, 0.17; P = 0.02). Our results suggest the two types of ATG may differentially influence transplant outcomes and it may optimize ATG selection according to the condition of patients.
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  • 文章类型: English Abstract
    Objective: To establish an acute graft-versus-host disease (aGVHD) model in aged mice after non-myeloablative haploidentical peripheral blood stem cell transplantation (haplo-PSCT). Methods: C57BL/6 (H-2b) male mice aged 6-8 weeks were used as donor mice, and CB6F1 (H-2b×d) female mice aged 14-16 months were used as recipient mice. The donor mice were injected subcutaneously with rehuman granulocyte-colony stimulating factor (rhG-CSF) 5 days before transplantation for hematopoietic stem cell mobilization.The recipient mice were divided into control group (CG), spleen cell low-dose group (SL), spleen cell medium-dose group (SM) and spleen cell high-dose group (SH) according to random number table method, with 16 rats in each group, all of which received total linear accelerator X-ray irradiation (TBI) with a total dose of 6 Gy. Peripheral blood mononuclear cells (PBMC) and spleen cells of different doses (0.5×107/each, 1.0×107/each and 2.0×107/each in SL group, SM group and SH group, respectively) were transfused through the tail vein within 4 hours after TBI, and only the same amount of normal saline was transfused in CG group. After transplantation, the survival and weight changes of mice in each group were observed for 30 days, and the changes of blood routine were monitored regularly. Mice peripheral blood was collected 21 days after transplantation to detect the chimerism rate of the donor. Hematoxylin-eosin staining was performed on the skin, liver and colon of mice 21 days after transplantation to analyze the histopathological changes of aGVHD target organs. Results: All the mice in each group were successfully transplanted. After TBI, the weight and activity of mice in all groups decreased, and the phenomenon of bone marrow suppression appeared. During the observation period, all mice in CG group and SL group survived, 3 mice in SM group died with survival time of (26.0±5.8) days, and 6 mice in SH group died with survival time of (20.9±7.3) days. The body weight of mice in SH group was lower than that in CG group, SL group and SM group 21days after transplantation [(25.0±0.7), (25.5±0.4), (25.0±1.4) vs (20.8±0.8) g, all P<0.05]. Compared with CG group, SL group and SM group, the levels of leukocyte, erythrocyte, hemoglobin and platelet in SH group decreased 21 days after transplantation (all P<0.05). There was no significant difference in donor chimerism rate among SL group, SM group and SH group [(95.8%±0.8%), (95.5%±1.4%) and (95.1%±1.3%), respectively, all P>0.05]. Compared with CG group, SL group and SM group, the tissue structure of aGVHD target organs in SH group was severely damaged, with a large number of inflammatory cells infiltratedand higher histopathological scores than SL group and SM group (all P<0.05). Conclusion: For aging CB6F1 mice, after 6 Gy TBI pretreatment with linear accelerator X-ray, PBMC (1×107/each) and spleen cells (2.0×107/each) were injected to successfully induce aGVHD model after non-myelablative haplo-PSCT.
    目的: 构建老龄小鼠非清髓性单倍体外周血造血干细胞移植(haplo-PSCT)后的急性移植物抗宿主病(aGVHD)模型。 方法: 选用6~8周龄C57BL/6(H-2b)雄性小鼠作为供鼠,14~16月龄CB6F1(H-2b×d)雌性老龄鼠作为受鼠。供鼠于移植前5 d皮下注射人粒细胞集落刺激因子(rhG-CSF)进行造血干细胞动员;将受鼠按随机数字表法分为对照组(CG)、脾细胞低剂量组(SL)、脾细胞中剂量组(SM)、脾细胞高剂量组(SH),每组各16只,均接受总剂量为6 Gy的直线加速器X射线全身照射(TBI),照射后4 h内经尾静脉输注外周血单个核细胞(PBMC)和不同剂量的脾细胞(SL组、SM组和SH组分别为0.5×107/只、1.0×107/只和2.0×107/只),CG组仅输注等量生理盐水。移植后观察各组受鼠的生存情况及体重变化,观察期为30 d,并定期监测小鼠血常规变化。移植后21 d取小鼠外周血检测供体嵌合率。移植后21 d取小鼠颈背部皮肤、肝脏、结肠组织行苏木精-伊红染色,分析aGVHD靶器官的组织病理学变化情况。 结果: 各组小鼠均移植成功。各组小鼠TBI后体重、活动度均下降,并出现骨髓抑制现象。观察期内CG组和SL组小鼠全部存活,SM组死亡3只,生存时间为(26.0±5.8)d,SH组小鼠死亡6只,生存时间为(20.9±7.3)d。SH组小鼠体重呈持续下降的趋势,移植后21 d体重低于CG组、SL组和SM组[分别为(25.0±0.7)、(25.5±0.4)、(25.0±1.4)比(20.8±0.8)g,均P<0.05]。移植后21 d,与CG组、SL组和SM组相比,SH组小鼠白细胞、红细胞、血红蛋白及血小板水平降低(均P<0.05)。SL组、SM组和SH组供体嵌合率差异无统计学意义[分别为(95.8%±0.8%)、(95.5%±1.4%)和(95.1%±1.3%),均P>0.05]。与CG组、SL组、SM组相比,SH组aGVHD靶器官组织结构破坏严重,大量炎性细胞浸润,且组织病理学评分高于SL组、SM组(均P<0.05)。 结论: 对于老龄CB6F1小鼠,给予直线加速器X线6 Gy TBI预处理之后,输注PBMC(1×107/只)、脾细胞(2.0×107/只)能成功诱导出非清髓性haplo-PSCT后aGVHD模型。.
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  • 文章类型: Journal Article
    背景:单采产品中造血干细胞的质量和数量对外周血造血干细胞移植(PB-HSCT)的成功至关重要。虽然流式细胞术测量CD34+细胞作为干细胞计数的黄金标准是劳动力和成本密集型的,建议将XNSysmex系列自动血液学分析仪(XN-HPC)评估的造血祖细胞数量作为替代标记.
    方法:我们评估了PB-HSCT期间来自同种异体供体和自体患者的单采术样品中XN-HPC和CD34+细胞计数的相关性和一致性。
    结果:在从健康供体(R=.852)而不是自体患者(R=.375)收集的收获物中,在XN-HPC和CD34+细胞计数之间观察到良好的相关性和一致性。亚组分析表明,当自体患者使用plerixafor作为额外的动员剂或被诊断为多发性骨髓瘤(MM)时,相关性尤其差。在同种异体移植的背景下,在来自非第一轮单采的样本中,相关系数甚至更好(R=.951),具有高白细胞(WBC)计数(R=.941),或在2周内成功植入(R=.895)。ROC分析表明,1127×106/L的最佳XN-HPC计数最好地预测CD34干细胞的足够产量,诊断灵敏度和特异性分别为92%和72%,分别(AUC=0.852)。
    结论:XN-HPC是用于评估同种异体但非自体HSCT中的干细胞收获率的足够的定量标志物。
    The quality and quantity of hematopoietic stem cells in apheresis products are essential to the success of peripheral blood hematopoietic stem cell transplantation (PB-HSCT). While the flow cytometry measurement of CD34+ cells as a golden standard for stem cell count is labor and cost-intensive, hematopoietic progenitor cell number evaluated by XN Sysmex series automated hematology analyzers (XN-HPC) is suggested as a surrogate marker.
    We evaluated the correlation and consistency of XN-HPC and CD34+ cell count in apheresis samples from both allogeneic donors and autologous patients during PB-HSCT.
    Good correlation and consistency were observed between XN-HPC and CD34+ cell counts in harvests collected from healthy donors (R = .852) rather than autologous patients (R = .375). Subgroup analysis showed that the correlation was especially poor when autologous patients used plerixafor as an additional mobilizer or were diagnosed with multiple myeloma (MM). In the setting of allogeneic transplantation, the correlation coefficients were even better in samples from non-first-round apheresis (R = .951), with high white blood cell (WBC) counts (R = .941), or having successful engraftment within 2 weeks (R = .895). ROC analysis suggested that an optimal XN-HPC count of 1127 × 106 /L best predicted a sufficient yield of CD34+ stem cells, with diagnostic sensitivity and specificity being 92% and 72%, respectively (AUC = 0.852).
    XN-HPC is a sufficient quantitative marker for stem cell assessment of harvest yield in allogeneic but not autologous HSCT.
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