Comparison between intermittent and continuous spectra optia leukapheresis systems for autologous peripheral blood stem cell collection

Terumo BCT recently introduced a new system for mononuclear cell (MNC) collection that uses a Spectra Optia apheresis machine equipped with a redesigned disposable kit and software program (version 11.2). It allows for the continuous collection of MNCs, unlike the original Spectra Optia system (version 7.2), which included a chamber for two‐step cell separation. The aim of this study was to compare the two apheresis systems in regard to specific performance parameters. A retrospective data analysis of 150 patients who had undergone peripheral blood stem cell collection between March of 2014 and May of 2015 at our institution was performed. For the matched comparison, patients were divided into two groups by diagnosis and by previous forms of therapy received: a homogeneous group of patients with multiple myeloma (MM) that had received first line therapy (“MM” group, n = 88) and a heterogeneous group that included all of the other patients (“other” group, n = 62). No significant differences in CD34+ collection yields between both collection regimens were found (p_MM = 0.19, p_other = 0.74) in either group. Moreover, similar performance ratios (collected/predicted CD34+ cell number in %) were observed (p_MM = 0.89, p_other = 0.1). No relevant variations in platelet or hemoglobin loss were found between the two systems. We conclude that the new continuous Spectra Optia MNC system is equally efficient in collecting CD34+ cells and can be used without sacrificing collection efficiency levels when treating a broad variety of autologous patients. J. Clin. Apheresis 32:27–34, 2017. © 2016 Wiley Periodicals, Inc.     

Dexmedetomidine for sedation during hematopoietic stem cell harvest apheresis and leukapheresis in the PICU: Guideline development

BackgroundHematopoietic stem cell (HSC) harvest apheresis and leukapheresis are performed in the pediatric intensive care unit (PICU) for high-risk pediatric patients who require procedural sedation. Patients need central access either with their own central lines, ports or require apheresis catheter (CVL) placement. Previously, patients were either awake or emerging from sedation on PICU admission. Uncertainty regarding procedural sedation plans caused delays initiating sedation and apheresis. A guideline was developed to standardize Dexmedetomidine (DEX) for procedural sedation. We investigated if guideline implementation would improve efficiency during PICU admission as demonstrated by shorter time intervals for initiation of sedation, apheresis, PICU length of stay and less alternative sedating medication.MethodsData was collected retrospectively from electronic health records of preguideline and post-guideline patients who were admitted to the PICU for sedated apheresis. We compared demographic and clinical characteristics, time intervals for sedation, apheresis, PICU length of stay, and sedation agents between the two groups using Fisher Exact tests and Mann-Whitney tests, as appropriate.ResultsThe groups did not differ in age or weight at the time of apheresis. All intervals of time compared were shorter post-guideline. Time intervals from admission to start of sedation, admission to start of apheresis, and admission to end of apheresis were statistically significantly different. The type and number of alternative sedating medications administered did not differ between the two groups.ConclusionThis guideline implementation improved efficiency during PICU admission. This study might have been too small to demonstrate statistically significant differences in other time intervals studied.     

The role of natalizumab in hematopoietic stem cell mobilization

The humanized monoclonal very late antigen 4 (VLA-4) antibody natalizumab is FDA approved for the treatment of patients with multiple sclerosis and Crohn's disease. In this review we focus on its role in the context of hemato-poietic stem cell transplantation and stem cell diseases. The use of natalizumab alone or in combination with either cytotoxic drugs or other antibodies might be a new modality for stem cell mobilization and a therapeutic option for patients with hematologic malignancies.     

单倍型供者性别与年龄对外周血造血干细胞采集质量的影响

目的观察健康供者性别与年龄因素对外周血造血干细胞采集质量的影响。方法回顾性分析2016年2月至2018年2月在河北燕达陆道培医院血细胞分离室接受外周血造血干细胞采集的311例单倍型健康供者的临床资料,根据供者性别分为男性组和女性组,根据年龄分为≤35岁组和>35岁组,比较各组采集物WBC、单个核细胞(MNC)%、CD34+%、MNC数、CD34+数。结果男性组采集物的WBC、CD34+%、MNC数、CD34+数与女性组比较,差异均有统计学意义(P<0.05)。男性组≤35岁者采集物的WBC、CD34+%、MNC数、CD34+数与女性组≤35岁者比较,差异均有统计学意义(P<0.05)。男性组>35岁者采集物的CD34+数、MNC%与女性组>35岁者比较,差异均有统计学意义(P<0.05)。男性组≤35岁者采集物的MNC%、CD34+%、CD34+数与>35岁者比较,差异均有统计学意义(P<0.05);女性组≤35岁者采集物的各项指标与>35岁者比较,差异均无统计学意义(P>0.05)。结论男性供者的外周血造血干细胞质量优于女性供者,≤35岁男性供者优于>35岁男性供者。     

A new model for predicting the timing of leukapheresis on the basis of CD34+ cell and hematopoietic progenitor cell levels

We developed a model (depending on peripheral CD34(+) cell count and hematopoietic progenitor cell count) to determine the optimal timing of 3-day leukapheresis in patients pretreated with chemotherapy and G-CSF. Marrow potentials were identified on the basis of three patterns of leukapheretic yield. Pattern 1 predicted good marrow potential. The positive predictive value of a first-day leukapheretic yield of >1 x 10(6) CD34(+) cells/kg (mean 3-day yield = 8.18 x 10(6) CD34(+) cells/kg, n = 11) was 100%. Pattern 2 predicted poor marrow potential. The negative predictive value of a 3-day leukapheretic yield of >1 x 10(6) CD34(+) cells/kg (3-day yield = 0.26 x 10(6) CD34(+) cells/kg, n = 1) was 100%. Pattern 3 met neither of the above criteria (mean 3-day yield = 1.37 x 10(6) CD34(+) cells/kg, n = 19). The marrow potential was borderline and patients could be further divided into two subgroups according to peripheral CD34(+) cell counts when WBC reached >10,000/microl. The mean yield differed significantly between pattern 1 and 3 (P < 0.001). For patients with good marrow potential, leukapheresis should begin as soon as the WBC count is >5,000/microl. Patients with borderline marrow potential may benefit from delaying leukapheresis until the WBC level is >10,000/microl and leukapheresis extended more than 3 days.     

异基因造血干细胞移植后供者外周血造血干细胞输注预防高危白血病复发

目的评估重组人粒细胞集落刺激因子(G-CSF)动员的供者外周血造血干细胞输注 (GPBSCI)作为一种早期过继性免疫治疗方法的有效性和安全性。方法 12例高危白血病患者同胞配型相合异基因造血干细胞移植(allo-HSCT)后接受了G-CSF动员的预防性GPBSCI。allo-HSCT前患者的诊断包括2例Ph 急性淋巴细胞白血病首次完全缓解(ALL-CR1),1例ALL-CR2,1例ALL合并顽固中枢神经系统白血病(CNSL),1例急性髓系白血病(AML)复发,1例AML合并CNSL,1例 AML-CR3,4例进展期慢性粒细胞白血病(CML)及1例骨髓增生异常综合征-难治性贫血伴幼稚细胞增多型(MDS-RAEB)。结果 12例患者共接受了16次GPBSCI,其中移植后90天( 90天)前接受 GPBSCI 5次,输注的单个核细胞(MNC)及CD3 细胞中位数分别为1．00(0．95-1．24)×108/kg和 0．53(0．39-0．63)×108/kg。 90天后接受GPBSCI 11次,输注两类细胞中位数分别为2．27(1．00- 4．30)×108/kg和1．15(0．55-2．10)×108/kg。输注后4例患者发生了Ⅰ或Ⅱ度急性移植物抗宿主病(GVHD),1例患者发生Ⅲ度急性GVHD。7例患者发生了慢性GVHD,其中4例为广泛型。2例患者未发生输注相关GVHD。未观察到GPBSCI相关的全血细胞减少。中位随访563(415-728)d,12 例高危白血病患者中有10例无病存活,2例死于白血病复发。结论预防性GPBSCI可以增强移植物抗白血病作用,相关不良反应小,可能成为改善高危白血病allo-HSCT预后的安全有效的手段。     

造血干细胞采集前后亲缘及非亲缘供者心理健康状态比较

背景：目前造血干细胞移植主要依靠在非血缘关系供者中寻找相合者。非亲缘造血干细胞捐献者的心理状态对于保证顺利完成移植,使受者得到有效治疗非常重要。目的：比较亲缘及非亲缘供者造血干细胞采集前后心理及生理健康状态。方法：分别在入院时,采集前（1 d）,采集后（一两天）,1个月后回访4个时间点对亲缘与非亲缘供者的心理状态（SCL-90症状自评量表评分）及一般生理指标（体温,呼吸,脉搏,血压）进行评估比较。结果与结论：在入院时,亲缘与非亲缘供者的心理健康水平差异无显著性意义（P＞0.05）;而在采集前、采集后,非亲缘供者的SCL-90总分、强迫、抑郁、焦虑、敌对、恐惧分值高于亲缘供者（P＜0.05）;1个月后回访,大多数分值差异无显著性意义（P＞0.05）。非亲缘和亲缘供者的生理指标平稳,但在采集前和采集后2个时间点,两组供者呼吸和收缩压差异有显著性意义。提示非亲缘供者在采集过程中的心理负荷较高,应给予针对性情绪疏导指导和心理防护。     

Crude collection efficiency of CD34+ hematopoietic stem cell apheresis

Understanding the apheresis principles for harvesting hematopoietic stem cells (HSCs) is critical for performing efficient procedures. However, despite significant advances in estimating the collection efficiency (CE) of aphereses, many confounding factors still need to be addressed in the classical calculations. The CE values are unrestricted, and many procedures exhibit CEs of a given cell population greater than 100%. This report introduces a simple equation that estimates the “crude” CE, which ranges from 0% to 100% and intrinsically considers the contribution of donor-related variables such as the pre-procedure mobilization and intra-apheresis recruitment of CD34⁺ cells (as a convenient marker for HSCs), as well as the performance of the apheresis system itself.     

Safety of large-volume leukapheresis for collection of peripheral blood progenitor cells

Large volume leukapheresis (LVL) reduces the number of procedures required to obtain adequate peripheral blood progenitor cells (PBPCs) for autologous hematopoietic reconstitution. LVL involves the processing of >15 L or 5 patient blood volumes using high flow rates. We report our experience with LVL evaluating its efficiency and adverse effects in 71 adult patients with hematologic or solid organ malignancies. All were mobilized with chemotherapy and granulocyte colony-stimulating factor (G-CSF). All collections used a double lumen apheresis catheter. Means values per LVL were as follows: blood processed, 24.6 L; patient blood volumes processed, 5.9; ACD-A used. 1.048 ml; heparin used, 6,148 units; collect time, 290 min; blood flow rate, 89 ml/min. Eighty percent of the collections were completed in one or two procedures to obtain ≥6.0 × 10⁸ MNCs/kg body weight. The most frequent side effect (39%) was parasthesia due to citrate-related hypocalcemia. This was managed with oral calcium supplements and or slower flow rates. Post-LVL electrolyte changes were generally asymptomatic. Prophylactic oral potassium supplements were administered in 57% of cases. Other reactions included hypotension (4%), prolonged parasthesia (1.4%), and headache (1.4%). Catheter problems in 9 (13%) of the procedures were attributed to clot formation (37%) or positional effects (63%). No bleeding occurred. Post-LVL decreases in hematocrit and platelet count averaged 3.5% and 46%, respectively. Six (4%) of the procedures required red blood cell transfusions. Platelet transfusions were given in 19 (13%) of the procedures. We conclude that adverse reactions with LVL are similar to those reported for conventional PBPC collections, making it safe and efficacious as an outpatient procedure. J. Clin Apheresis 12:10–13, 1997. © 1997 Wiley-Liss, Inc.     

13例原发性系统性淀粉样变性患者行自体外周血造血干细胞采集的护理体会

目的探讨原发性系统性淀粉样变性（AL）患者行自体外周血造血干细胞采集中的护理要点。方法 13例AL患者在本科干细胞移植病房行自体外周血造血干细胞采集,所有患者均经肾活检明确诊断,采用单用粒细胞刺激因子（G-CSF）方案采集干细胞,人均采集2次。结果所有患者均成功采集足够干细胞,主要并发症为低钙血症、低钾血症及血小板减低。采集CD34＋细胞数（2.00~8.36）×106/kg,平均（4.02±2.01）×106/kg。结论对于严格选择的AL患者,自体外周血干细胞移植（AHSCT）治疗是一种有效的治疗手段,采集足量的造血干细胞是成功行干细胞移植的重要前提。     

Erythropoiesis-stimulating agents in allogeneic and autologous hematopoietic stem cell transplantation

Introduction: Erythropoiesis-stimulating agents (ESAs) are used in treating cancer- and chemotherapy-induced anemia with the aim of accelerating the recovery of red blood cells (RBCs), reduce the risks associated with RBC transfusions and improve quality of life.

Areas covered: A systematic review has been conducted to examine the current evidence for the efficacy and safety of using ESAs in hematopoietic stem cell transplants (HSCTs).

Expert opinion: Despite the international recommendations for the use of ESAs in treating different malignancies, there is a lack of guidelines for their use in patients undergoing HSCT. An evaluation of published clinical trials shows that there are no available powerful studies concerning the use of ESAs in this setting, with only heterogeneous and small numbers of patients reported so far. Nevertheless, the more robust and intriguing of these data suggest that the ESA’s administration at an appropriate time after the infusion of stem cells may be effective both in autologous and allogeneic HSCTs. New guidelines are required, overseen by an expert in the in the field of stem cell transplantation.     

ABO血型不合的异基因造血干细胞采集及移植效果研究

本研究评价COBE Spectra血细胞分离机按干细胞采集程序采集HLA配型相合、ABO血型不合供者外周血造血干细胞的效能,观察未去除红细胞和(或)血浆进行异基因外周血干细胞移植的效果。应用COBE Spectra血细胞分离机的自动干细胞采集程序采集28例异基因供者外周血干细胞,并选用同期ABO血型相合15例作对照。检测采集物有核细胞(NC)数、单个核细胞(MNC)比例及CD34+细胞计数,观察造血功能重建情况和转变为供者血型所需要的时间。结果表明,ABO血型不合和相合组采集物中的NC、CD34+细胞数、MNC比例无统计学差异(p>0.05)。ABO血型不合组和相合组中性粒细胞和血小板恢复的时间无统计学差异(p>0.05)。14例ABO血型主要不合患者,红系造血明显延迟,ABO血型不合组28名患者于移植后35-193天血型成功转变为供者型,和ABO血型相合组相比均有统计学差异(p<0.01)。结论:ABO血型不合不是异基因造血干细胞移植的障碍,主要不合可能是红系造血明显延迟的主要原因。     

持续 Wnt 信号通路激活促进胚胎干细胞源造血干细胞的增殖简

背景：如何提高胚胎干细胞诱导效率、促进胚胎干细胞源造血干细胞体外增殖成为目前急需解决的课题。目的：以外源性Wnt3a作为诱导剂,激活培养中的小鼠胚胎干细胞Wnt/β-catenin信号通路,观察该通路的激活是否促进胚胎干细胞向造血祖细胞的定向分化。方法：用外源性wnt3a（100μg/L）持续作用ES-E14TG2a小鼠胚胎干细胞21 d,通过细胞免疫荧光及蛋白免疫印迹检测细胞内β-catenin蛋白含量,QRT-PCR检测Wnt下游靶标基因的表达量来确定经典Wnt/β-catenin信号通路是否被激活,然后采用单层贴壁培养法诱导其向造血干细胞分化,流式细胞仪检测造血发育相关表面标志CD34＋/Sca-1＋,同时以QRT-PCR法检测造血相关基因的表达情况。结果与结论：ES-E14TG2a小鼠胚胎干细胞经wnt3a（100μg/L）连续培养21 d后发现β-catenin蛋白在细胞内积累;Wnt信号通路的下游靶标基因Pitx2、Frizzled、Sox17、Oct4的表达量均出现不同程度的增加,可见经典 Wnt/β-catenin 信号通路有被激活;单层贴壁培养法诱导其向造血干细胞分化的过程中检测到CD34＋/Sca-1＋细胞含量在14 d时占总细胞量高达20.2%,而对照组的仅占11.9%。造血相关基因骨形态发生蛋白4、FLK2及CD34的表达量均增加,而Smad5的表达则明显受到抑制。说明Wnt3a持续作用可激活Wnt/β-catenin信号通路,并促进ES-E14TG2a小鼠胚胎干细胞向造血干细胞的定向分化。     

造血干细胞移植护理进展

从临床观察、护理管理、护理服务方面综述造血干细胞移植护理进展。     

Peripheral blood stem cell grafts in allogeneic hematopoietic cell transplantation: It is not all about the CD34+ cell dose

Allogeneic Hematopoietic Cell Transplantation is a curative approach in various malignant and non-malignant disorders. The majority of adult transplants in the current era are performed using mobilized stem cells, harvested from the peripheral blood by leukapheresis. Peripheral blood stem cell (PBSC) collections are designed to target a dose of stem cells that will result in safe engraftment and hematopoietic recovery; however, 99 % of the cells contained in a PBSC graft are not stem cells and a growing number of studies attempt to characterize the associations between graft composition and transplant outcomes. A better understanding of the impact of the quantity and quality of various cell types in PBSC grafts may lead to development of novel collection strategies or improved donor selection algorithms. Here we review relevant findings from recent studies in this area.