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Pub Date : 2000-12-01 DOI: 10.1016/S0955-3886(00)00112-0
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引用次数: 0
Peripheral blood stem cell collection: the interaction of technology, procedure, and biological factors 外周血干细胞收集:技术、程序和生物因素的相互作用
Pub Date : 2000-10-01 DOI: 10.1016/S0955-3886(00)00077-1
Jeane Hester

Centrifugal technology, continuous flow and discontinuous flow, has served as the technology platform for extracting cell concentrates of interest from peripheral blood (PB) for patient therapy for the past 35–40 yr. Models for procedure outcome exist for collection of normal donor (ND) platelet and granulocyte concentrates that integrate: (1) biological variables (pre-procedure PB cell concentration, the total circulating quantity of cells, donor/patient blood volume (BV)), (2) device efficiency, and (3) procedure parameters such as total blood processed (TBP), and in the case of cytoreductions – the volume collected. (cf. Hester J, Kellogg R, Mulzet A, et al., Blood (54) (1979) 254; Hester J, Ventura G, J Clin Apheresis (4) (1988) 188.) To date, no predictive CD34+ yield algorithm integrating these three variables has been formulated that could be applied prospectively for individual ND or patients (PT). There are economic, toxicity and statistical comparison benefits to be derived from generating such an algorithm.

A small pilot study is presented with a brief review of current publications that suggest the circulating quantity of CD34+ cells available to be collected and the quantity mobilized during leukapheresis are the major contributing factors to CD34+ yield, somewhat obscuring the role of the total blood processed (TBP). Intraprocedure CD34+ cell mobilization, incompletely characterized to date, appears to be a dynamic nonlinear process, as the harvested yield does not rise proportionally as the fraction of BV processed increases. And, like the pre-procedure PB CD34+ concentration and total circulating quantity, CD34+ mobilization during leukapheresis probably relates to prior treatment and the priming regimen. Studies that provide: (1) separate analyses of PT populations divided according to chemotherapy toxicity factors; (2) design and implementation of optimal priming regimens with respect to dose ‘intensity’ of both growth factors and chemotherapy; and (3) standardization of laboratory assays of CD34+ enumeration seem essential to generating a predictive algorithm.

在过去的35-40年里,离心技术,连续流动和不连续流动,已经成为从外周血(PB)中提取感兴趣的细胞浓缩物的技术平台,用于患者治疗。收集正常供体(ND)血小板和粒细胞浓缩物的手术结果模型包括:(1)生物学变量(术前PB细胞浓度,细胞循环总量,供者/患者血容量(BV)),(2)设备效率,(3)程序参数,如处理的总血液(TBP),在细胞减少的情况下-收集的体积。(cf. Hester J, Kellogg R, Mulzet A, et ., Blood (54) (1979) 254;张建军,张建军,张建军,等。临床血液学杂志(4)(1988)188。到目前为止,还没有整合这三个变量的预测CD34+产率算法,可以应用于个体ND或患者(PT)。生成这样的算法在经济、毒性和统计比较方面都有好处。一项小规模的试点研究简要回顾了当前的出版物,表明可收集的CD34+细胞的循环数量和白细胞分离过程中动员的数量是CD34+产量的主要影响因素,在一定程度上模糊了总血液处理(TBP)的作用。过程中CD34+细胞的动员,迄今尚未完全表征,似乎是一个动态的非线性过程,因为收获的产量并没有随着加工的BV比例的增加而成比例地增加。而且,与术前外周血CD34+浓度和总循环量一样,白细胞分离期间CD34+的动员可能与先前的治疗和启动方案有关。研究提供:(1)根据化疗毒性因素对PT人群进行单独分析;(2)根据生长因子和化疗的剂量“强度”设计和实施最佳启动方案;(3) CD34+计数的实验室分析标准化似乎对生成预测算法至关重要。
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引用次数: 15
Adoptive allogeneic immunotherapy – history and future perspectives 过继性异体免疫治疗的历史和未来展望
Pub Date : 2000-10-01 DOI: 10.1016/S0955-3886(00)00078-3
Michael Schleuning

For more than 30 yrs allogeneic hematopoietic stem cell transplantations have been successfully performed in patients with hematologic malignancies and bone marrow aplasia. Over the years the field of transplantation has changed dramatically. More and more unrelated donors became available, regimens for haploidentical transplantations were introduced and G-CSF mobilized peripheral blood stem cells and fetal cells from umbilical cord became available as alternate sources of hematopoietic stem cells. However, especially the introduction of donor lymphocyte infusions (DLI) for the successful treatment of leukemic relapses after allogeneic stem cell transplantations improved our understanding of transplantation immunology and opened amazing perspectives in allogeneic transplantation. It was long believed, that myeloablative therapy with high-dose chemotherapy and total body irradiation (TBI) are the sole antileukemic principles in allogeneic transplantations. But by now it became clear, that donor lymphocytes exert a very potent antileukemic effect, now referred as the graft-versus-leukemia (GVL) or graft-versus-malignancy (GVM) reaction. The efficacy of DLI in controlling leukemic relapses suggests that myeloablative therapy is not essential for long-term disease control. By exploiting the GVL or GVM reaction more intensively the role of chemotherapy and TBI is changing to immunosuppression. Sufficient immunosuppression to allow grafting, however, can be achieved with much lower doses as those which have been used in conventional transplants. Therefore allogeneic transplants have become also available for the elderly or for patients with concurrent medical conditions, which would have excluded them from conventional transplants. Moreover, this allogeneic transplantation strategy with reduced intensity conditioning is now also under investigation in patients with susceptible solid tumors and autoimmune diseases. However, one major obstacle in allogeneic transplantations, namely the graft-versus-host disease (GVHD), remains to be solved.

30多年来,同种异体造血干细胞移植已经成功地应用于血液恶性肿瘤和骨髓发育不全患者。多年来,移植领域发生了巨大的变化。越来越多的非亲属供体可用,单倍体移植方案被引入,G-CSF动员的外周血干细胞和来自脐带的胎儿细胞成为造血干细胞的替代来源。然而,特别是引入供体淋巴细胞输注(DLI)成功治疗同种异体干细胞移植后白血病复发,提高了我们对移植免疫学的认识,并为同种异体移植开辟了令人惊叹的前景。长期以来,人们一直认为高剂量化疗和全身照射(TBI)的清髓治疗是同种异体移植中唯一的抗白血病原则。但现在已经很清楚,供体淋巴细胞发挥了非常有效的抗白血病作用,现在被称为移植物抗白血病(GVL)或移植物抗恶性肿瘤(GVM)反应。DLI在控制白血病复发方面的疗效表明,清髓治疗对于长期疾病控制不是必需的。通过更强烈地利用GVL或GVM反应,化疗和TBI的作用正在向免疫抑制转变。然而,与传统移植中使用的剂量相比,可以用更低的剂量实现足够的免疫抑制以允许移植。因此,同种异体移植也可用于老年人或同时患有疾病的患者,这些患者将被排除在常规移植之外。此外,这种降低强度调节的同种异体移植策略目前也在易感实体瘤和自身免疫性疾病患者中进行研究。然而,同种异体移植的一个主要障碍,即移植物抗宿主病(GVHD),仍有待解决。
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引用次数: 21
Leucodepletion process performance variation: is it dependent on the batch of filters, the processing centre or the counting technology? 滤光工艺性能变化:取决于滤光片的批次、处理中心还是计数技术?
Pub Date : 2000-10-01 DOI: 10.1016/S0955-3886(00)00075-8
Neil Beckman, Jerard Seghatchian

The aim of this retrospective study was to determine whether variations in the enumerated white cell contamination of leucocyte-depleted products was caused by the filter batch, the processing centre or by counting technology related issues. The influence of donor variation is also considered. The results suggest that for some red cell processes, variation is mainly the result of counting technology differences. Other products do not display similar trends though all leucodepletion processes may give rare high white count failures due to donor related issues, though defective filter batch cannot be excluded requiring continual review.

这项回顾性研究的目的是确定白细胞减少产品中所列举的白细胞污染的变化是由过滤器批次、处理中心还是计数技术相关问题引起的。还考虑了供体变异的影响。结果表明,对于某些红细胞过程,变异主要是计数技术差异的结果。其他产品没有显示出类似的趋势,尽管由于供体相关问题,所有的白细胞消耗过程可能会出现罕见的高白细胞计数失败,但不能排除有缺陷的过滤器批次,需要持续审查。
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引用次数: 4
IVIG as a nonspecific accelerator of restitutio ad integrum IVIG作为恢复和积分的非特异性加速器
Pub Date : 2000-10-01 DOI: 10.1016/S0955-3886(00)00080-1
E Rewald
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引用次数: 1
Early total white blood cell recovery is a predictor of low number of apheresis and good CD34+ cell yield 早期的总白细胞恢复是低单采数和良好的CD34+细胞产量的预测因子
Pub Date : 2000-10-01 DOI: 10.1016/S0955-3886(00)00072-2
J.F.C Marques , A.C Vigorito , F.J.P Aranha , I Lorand-Metze , E.C.M Miranda , E.C Lima Filho , M Valbonesi , G Santini , C.A De Souza

Objective. We analysed peripheral blood progenitor cell (PBPC) mobilisation and collection in order to assess the main factors related to CD34+ cell yields in patients affected by haematological malignancies.

Patients and Methods. The features of CD34+ cell mobilisation of patients with haematological malignancies that underwent autologous bone marrow transplantation were examined. Mobilisation chemotherapy consisted mainly of cyclophosphamide (CY) 4 or 7 g/m2 followed by growth factors. Leukapheresis was started when the WBC counts reached 1.0 × 109/l with the aim to collect at least 5 × 106 CD34+ cells/kg body weight. The aphereses were performed on continuous-flow blood cell separators. The analysed variables were: age, diagnosis, CT mobilisation regimen, type of growth factor, number of previous CT lines, prior radiotherapy, days for WBC recovery and number of aphereses procedures to achieve the target of CD34+ cells.

Results. There were 41 consecutive patients (26 M/15 F): 21 non-Hodgkin’s lymphoma (NHL), 15 Hodgkin’s disease (HD), two chronic myeloid leukaemia (CML) and three multiple myeloma (MM). Eleven patients could not collect the proposed threshold of CD34+ cells. CY 4 mobilised patients recovered WBC counts in less days (P=0.03). By ANOVA, the days to WBC recovery had a linear function of the predictors “number of aphereses” and “type of mobilisation CT” (coefficients: 0.86 and 0.95, respectively). For the number of aphereses and WBC recovery after CT mobilisation, we obtained a correlation coefficient of 0.36 (P=0.02).

Conclusion. This study shows that it is feasible to mobilise and collect PBPC in patients previously treated with CT with or without RT. There was a linear correlation between the days for WBC recovery and the number of aphereses needed to collect the target number of CD34+ cells. The study suggests that early WBC recovery, using mainly CY 4 mobilisation chemotherapy, is an important predictor of a low number of aphereses to achieve a good CD34+ yield.

目标。我们分析了外周血祖细胞(PBPC)的动员和收集,以评估血液学恶性肿瘤患者中与CD34+细胞产量相关的主要因素。患者和方法。研究了恶性血液病患者自体骨髓移植后CD34+细胞动员的特点。动员化疗主要是环磷酰胺(CY) 4或7 g/m2,其次是生长因子。白细胞计数达到1.0 × 109/l时开始采白细胞,目的是每公斤体重收集至少5 × 106个CD34+细胞。在连续流式血细胞分离器上进行分离。分析的变量为:年龄、诊断、CT动员方案、生长因子类型、既往CT线数、既往放疗、白细胞恢复天数和达到CD34+细胞目标的细胞学操作次数。41例患者(26例M/15例F): 21例非霍奇金淋巴瘤(NHL), 15例霍奇金病(HD), 2例慢性髓性白血病(CML)和3例多发性骨髓瘤(MM)。11例患者无法收集到CD34+细胞的阈值。cy4动员患者WBC计数在较短时间内恢复(P=0.03)。通过方差分析,到白细胞恢复的天数与预测因子“血小板数量”和“活动CT类型”呈线性关系(系数分别为0.86和0.95)。CT动员后白细胞恢复与血小板数量的相关系数为0.36 (P=0.02)。这项研究表明,在之前接受过CT治疗或不接受rt治疗的患者中,动员和收集PBPC是可行的。白细胞恢复的天数与收集CD34+细胞目标数量所需的细胞质数量呈线性相关。该研究表明,主要使用cy4动员化疗的早期WBC恢复是实现良好CD34+产率的低数量细胞质的重要预测因子。
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引用次数: 19
Editorial: haematopoietic stem cell transplantation 社论:造血干细胞移植
Pub Date : 2000-10-01 DOI: 10.1016/S0955-3886(00)00076-X
Peter Jacobs, Lucille Wood, Ramsey Sabit
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引用次数: 2
血液学MCS+ C版在血小板穿刺期间间断自动补钙。
Pub Date : 2000-10-01 DOI: 10.1016/S0955-3886(00)00081-3
M Valbonesi, R Bruni, G Florio, A Marghero, A Telani, I Varinelli
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引用次数: 3
Difficulties in the management of an incomplete form of refractory thrombotic thrombocytopenic purpura, the usefulness of vincristine 难治性不完全血栓性血小板减少性紫癜的治疗困难,长春新碱的有效性
Pub Date : 2000-10-01 DOI: 10.1016/S0955-3886(00)00073-4
P Chamouni , P Lenain , G Buchonnet , V Merle , C Bourgain , A Boyer , C Girault , P Czernichow

Background: Although several etiologies can be identified in thrombotic thrombocytopenic purpura (TTP), idiopathic cases are still frequent. Incomplete forms are more rare. Currently, the diagnosis may be made in cases of thrombocytopenia and microangiopathic hemolytic anemia. According to the literature, mortality and morbidity are significantly improved with plasma exchange. However, treatment in refractory forms remains problematic.

Case Report: A 33-year old woman presented with an incomplete form of TTP, refractory to a combination of therapeutics. The patient underwent plasma infusion, plasma exchange, and then was started on corticosteroids. She also received intravenous immunoglobulins and antiplatelet agents in close proximity to vincristine (Oncovin®) infusion. The main biological indicators used were the platelet count, hematocrit, LDH, and the presence of schistocytes. Following vincristine treatment, the patient’s condition rapidly improved.

Conclusion: Vincristine administered after the failure of standard therapeutics was effective in this refractory form of TTP.

背景:虽然血栓性血小板减少性紫癜(TTP)有多种病因,但特发性病例仍然很常见。不完整的表单更为罕见。目前,诊断可能是在血小板减少症和微血管病溶血性贫血的情况下作出的。根据文献,血浆置换可显著改善死亡率和发病率。然而,难熔形式的治疗仍然存在问题。病例报告:一名33岁女性,呈现不完全TTP形式,对联合治疗难治性。患者接受血浆输注、血浆置换,然后开始使用皮质类固醇。她还接受了静脉注射免疫球蛋白和抗血小板药物,接近长春新碱(Oncovin®)输注。使用的主要生物学指标是血小板计数、红细胞压积、LDH和血吸虫细胞的存在。经长春新碱治疗后,患者病情迅速好转。结论:在标准治疗失败后给予长春新碱对这种难治性TTP有效。
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引用次数: 12
Three episodes of delayed hemolytic transfusion reactions due to multiple red cell antibodies, anti-Dia, anti-Jkb and anti-E 由于多种红细胞抗体,抗dia,抗jkb和抗e引起的延迟溶血性输血反应三次
Pub Date : 2000-10-01 DOI: 10.1016/S0955-3886(00)00074-6
H Yasuda , H Ohto , O Yamaguchi , S Sakuma , T Suzuki , M Mita , H Tsuneyama , M Uchikawa

There is no report in which three episodes of delayed hemolytic transfusion reaction (DHTR) occurred from multiple antibodies to red cells (RBCs) in the course of treatment of a patient. This paper describes episodes of anemia and hyperbilirubinemia in concert with the development of three alloantibodies in a multiple transfused patient. The patient was a 71-year-old male suffering from valvular heart disease and hemophilia B with a history of transfusions. Although he received compatible RBCs from 14 donors as judged by a crossmatch test using the albumin–antiglobulin method, three episodes of DHTR occurred after surgery. The first hemolytic episode on day 7 after surgery was due to anti-Dia because of clinical and laboratory evidence which included jaundice, sudden increases in total bilirubin (T-Bil) and lactate dehydrogenase (LD) levels, and a decrease (2.2 g/dl) in hemoglobin (Hb) level. The second hemolytic episode on day 16 resulted from newly producted anti-Jkb. The patient experienced fever, fatigue, nausea and anorexia, and laboratory data showed a second increase in T-Bil, a second decrease (3 g/dl) in Hb, and moderate elevations of blood urea nitrogen (BUN) and creatinine (CRE) levels. The third hemolytic episode on day 39 was due to anti-E. The patient complained of fever and fatigue and had a third unexplained drop (1.5 g/dl) in Hb despite no bleeding. This is the first reported case in which three episodes of DHTR occurred from different red cell antibodies.

在患者的治疗过程中,没有发生三次延迟溶血性输血反应(DHTR)的报告,这些反应是由红细胞(rbc)的多种抗体引起的。本文描述了贫血和高胆红素血症的发作,在协调发展的三个同种异体抗体在多次输血的病人。患者为71岁男性,患有心脏瓣膜病和B型血友病,有输血史。尽管通过白蛋白-抗球蛋白交叉配型试验,他接受了14个供体的相容红细胞,但手术后发生了三次DHTR。术后第7天的第一次溶血发作是由于抗dia,因为临床和实验室证据包括黄疸,总胆红素(T-Bil)和乳酸脱氢酶(LD)水平突然升高,血红蛋白(Hb)水平下降(2.2 g/dl)。第16天第二次溶血是由新产生的抗jkb引起的。患者出现发热、疲劳、恶心和厌食,实验室数据显示T-Bil第二次升高,Hb第二次下降(3 g/dl),血尿素氮(BUN)和肌酐(CRE)水平中度升高。第39天第三次溶血是由于抗e。患者主诉发热和疲劳,并有第三次不明原因的Hb下降(1.5 g/dl),尽管没有出血。这是首次报道的由不同红细胞抗体引起三次DHTR发作的病例。
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引用次数: 15
期刊
Transfusion science
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