Gasová Zdenka, Marinov Iuri, Vodvárková Sárka, Böhmová Martina, Bhuyian-Ludvíková Zdenka
Transfusion Department, Institute of Hematology and Blood Transfusion, U nemocnice 1, Prague 2, 128 20 Czech Republic.
Transfus Apher Sci. 2005 Apr;32(2):167-76. doi: 10.1016/j.transci.2004.10.018.
Transplantations of autologous and allogeneic peripheral blood progenitor cells (PBPC) are able to assure a complete hematopoietic and immunologic reconstitution in patients. PBPC are collected by leukapheresis technique after prior mobilization therapy, but procedures and results remain still highly variable and are poorly characterized. An optimum regimen for PBPC collections has not yet been recommended, but 2-3 total blood volumes (TBV) of the donor or patient are regarded as a standard. Another promising technique is large volume leukapheresis (LVL) with processing of 3-6 TBV of donor or patient. The aim of this paper is to find the most efficient and safe collection technique for an individual donor or patient and, consequently minimize the number of procedures required. Finding the optimal collection procedure would be helpful while considering which method would be preferred in an individual donor or patient with respect to the result of mobilization, health state and required yield of CD 34+ cells for transplantation. We evaluated the results in a total of 134 standard and LVL procedures, which were performed in 21 well mobilized donors (Group I), in 65 well mobilized patients (Group II), and in 14 weakly mobilized patients (Group III) with hemato-oncological diseases. A precollection concentration of CD 34+ cells in peripheral blood higher than 20 x 10(3)/mL was considered to be the criterion for efficient mobilization. Such levels of concentration indicating the start of PBPC collections could be easily reached in Group I of donors and Group II of well mobilized patients. Heavily pretreated patients at advanced stages of disease (Group III) did not respond to mobilization sufficiently and had a concentration of CD 34+ cells lower than 20x10(3)/mL. LVL technique made it possible to obtain higher numbers of CD 34+ cells than in the standard collection in well mobilized donors (Group I), well mobilized patients (Group II), and even in weakly mobilized patients in Group III. In donors and well mobilized patients (Group I and Group II) it was possible to collect sufficient amounts of CD 34+ cells for allogeneic or for autologous transplantation from one LVL collection. The median yield of CD 34+ cells from one LVL collection was 5.5 x 10(6)/kg b.w. in donors, and 6.0 x 10(6)/kg b.w. in well mobilized patients. Due to the linear dependence of the yield of collected CD 34+ cells on the concentration of CD 34+ cells in blood, it can be used as a simple prediction of the success of collection in Group II (correlation coefficient 0.93 for standard procedures, and correlation coefficient 0.88 for LVL). In Group III of weakly mobilized patients the standard collections were usually ineffective and the relationship between the yield of CD 34+ cells/kg in the product and the precollection concentration of CD 34+ cells was much less significant (correlation coefficient 0.56 for standard procedures and correlation coefficient 0.66 for LVL). The median of CD 34+ cells collected from one standard procedure was only 0.7 x 10(6)/kg but using LVL the median increased to 1.4 x 10(6)/kg. Our results prove that the yield of CD 34+ cells in the product can be enhanced by large volume leukapheresis (LVL). Based on the results obtained, we recommend LVL in all donors and patients who can tolerate it due to a greater chance of collecting higher yields of progenitor cells while minimizing adverse reactions. LVL procedures should also be preferred in weakly mobilized patients where it is not possible to collect sufficient amounts of CD 34+ cells for transplantation using the standard regime. In weakly mobilized patients LVL provides a greater chance to at least collect a minimum amount of CD 34+ cells necessary. LVL should be used in circumstances where extremely high doses of CD 34+ cells has to be prepared, e.g. planned "tandem" transplantations or manipulations with a graft in which a significant loss of cells is expected.
自体和异体外周血祖细胞(PBPC)移植能够确保患者实现完全的造血和免疫重建。PBPC是在预先进行动员治疗后通过白细胞分离术采集的,但程序和结果仍然高度可变且特征描述不佳。尚未推荐PBPC采集的最佳方案,但供体或患者的2 - 3个全血容量(TBV)被视为标准。另一种有前景的技术是大容量白细胞分离术(LVL),可处理供体或患者3 - 6个TBV的血液。本文的目的是为个体供体或患者找到最有效和安全的采集技术,从而尽量减少所需的程序数量。在考虑针对个体供体或患者,就动员结果、健康状况以及移植所需的CD 34 +细胞产量而言哪种方法更优时,找到最佳采集程序会有所帮助。我们评估了总共134例标准和LVL程序的结果,这些程序在21例动员良好的供体(I组)、65例动员良好的患者(II组)以及14例血液肿瘤疾病动员不佳的患者(III组)中进行。外周血中CD 34 +细胞的采集前浓度高于20×10³/mL被认为是有效动员的标准。I组供体和II组动员良好的患者很容易达到指示开始PBPC采集的这种浓度水平。处于疾病晚期且预处理严重的患者(III组)对动员反应不足,CD 34 +细胞浓度低于20×10³/mL。LVL技术使得在动员良好的供体(I组)、动员良好的患者(II组)以及甚至III组动员不佳的患者中能够获得比标准采集更多数量的CD 34 +细胞。在供体和动员良好的患者(I组和II组)中,从一次LVL采集中就有可能采集到足够量的CD 34 +细胞用于异体或自体移植。一次LVL采集的CD 34 +细胞中位数产量在供体中为5.5×10⁶/kg体重,在动员良好的患者中为6.0×10⁶/kg体重。由于采集的CD 34 +细胞产量与血液中CD 34 +细胞浓度呈线性相关,它可用于简单预测II组的采集成功率(标准程序的相关系数为0.93,LVL的相关系数为0.88)。在III组动员不佳的患者中,标准采集通常无效,产品中CD 34 +细胞/kg产量与采集前CD 34 +细胞浓度之间的关系不太显著(标准程序的相关系数为0.56,LVL的相关系数为0.66)。从一次标准程序采集中采集的CD 34 +细胞中位数仅为0.7×10⁶/kg,但使用LVL时中位数增加到1.4×10⁶/kg。我们的结果证明,大容量白细胞分离术(LVL)可提高产品中CD 34 +细胞的产量。基于所获得的结果,我们建议在所有能够耐受的供体和患者中采用LVL,因为有更大机会采集到更高产量的祖细胞,同时将不良反应降至最低。在动员不佳的患者中,如果使用标准方案无法采集到足够量的用于移植的CD 34 +细胞,也应首选LVL程序。在动员不佳的患者中,LVL提供了更大机会至少采集到所需的最低量CD 34 +细胞。在必须准备极高剂量CD 34 +细胞的情况下,例如计划进行“串联”移植或对预期会有大量细胞损失的移植物进行操作时,应使用LVL。