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异基因外周血祖细胞移植后的免疫重建:CD34+阳性选择移植物受者与未处理移植物受者的比较。

Immune reconstitution following allogeneic peripheral blood progenitor cell transplantation: comparison of recipients of positive CD34+ selected grafts with recipients of unmanipulated grafts.

作者信息

Martínez C, Urbano-Ispizua A, Rozman C, Marín P, Rovira M, Sierra J, Montfort N, Carreras E, Montserrat E

机构信息

Hematology Department, Postgraduate School of Hematology Farreras-Valentí, Institut d'Investigacions Biomédiques August Pí i Sunyer, University of Barcelona, Spain.

出版信息

Exp Hematol. 1999 Mar;27(3):561-8. doi: 10.1016/s0301-472x(98)00029-0.

Abstract

We compared the kinetic recovery of lymphocytes and their subsets in two groups of patients submitted to allogeneic peripheral blood progenitor cell transplantation (allo-PBT): those receiving lymphocyte-depleted leukaphereses by positive selection of CD34+ cells (group 1, n = 18) and those receiving unmanipulated leukaphereses (group 2, n = 15). Patients were conditioned with cyclophosphamide (120 mg/kg) and fractioned total body irradiation (13 Gy, group 1; 12 Gy, group 2). The mean number (x 10(6)/kg) of CD34+ and CD3+ cells infused was 4.0 and 0.67, respectively, in group 1 patients, and 4.7 and 274, respectively, for group 2 patients. Graft-versus-host disease prophylaxis consisted of cyclosporin A + methylprednisolone for group 1 and cyclosporin A + methotrexate for group 2. Median follow-up was 7 months (range 2-8 months) for both groups. During the first 6 months post-transplant, CD4+ cell counts were lower in group 1 as compared with group 2 (p = 0.014, 0.010, 0.011, 0.0003, and 0.052 at 0.5, 1, 2, 3, and 6 months, respectively), whereas there was no difference at 8 months. The number of CD4+CD45RA+ cells was very low throughout the study in both groups, being lower in group 1 than in group 2, especially during the first 3 months post-transplant (p = 0.007 and 0.0006 at 1 and 3 months). Normal levels of CD8+ cells were reached by 1 month post-transplant in both groups. TCR gamma delta + cell counts were lower in group 1 than in group 2 during the first 4 months post-transplant (p = 0.001, 0.004, and 0.04 at 1, 3, and 4 months). A normal number of natural killer cells (CD3-CD56+) was achieved 1 month post-transplant in both groups. B lymphocytes (CD19+) showed low or undetectable counts throughout the first 4 months in both groups, achieving the normal range at 8 months. These results show that, during the first 6 months following allo-PBT with CD34+ selected grafts, the number of CD4+, CD4+CD45RA+, and TCR gamma delta + cells is significantly lower than after unmanipulated allo-PBT; these differences disappeared at 8 months. In contrast, there are no differences between transplant groups in the recovery of CD8+, CD19+, and natural killer cells.

摘要

我们比较了两组接受异基因外周血祖细胞移植(allo - PBT)患者淋巴细胞及其亚群的动力学恢复情况:一组是通过阳性选择CD34⁺细胞进行淋巴细胞清除的白细胞单采术(第1组,n = 18),另一组是接受未处理的白细胞单采术(第2组,n = 15)。患者均接受环磷酰胺(120 mg/kg)预处理及分次全身照射(第1组13 Gy,第2组12 Gy)。第1组患者输注的CD34⁺和CD3⁺细胞的平均数量(×10⁶/kg)分别为4.0和0.67,第2组患者分别为4.7和274。第1组移植物抗宿主病预防方案为环孢素A + 甲泼尼龙,第2组为环孢素A + 甲氨蝶呤。两组的中位随访时间均为7个月(范围2 - 8个月)。移植后的前6个月,第1组的CD4⁺细胞计数低于第2组(分别在0.5、1、2、3和6个月时,p值分别为0.014、0.010、0.011、0.0003和0.052),而在8个月时无差异。在整个研究过程中,两组CD4⁺CD45RA⁺细胞数量都非常低,第1组低于第2组,尤其是在移植后的前3个月(1个月和3个月时p值分别为0.007和0.0006)。两组在移植后1个月时CD8⁺细胞水平均恢复正常。移植后的前4个月,第1组的TCRγδ⁺细胞计数低于第2组(1个月、3个月和4个月时p值分别为0.001、0.004和0.04)。两组在移植后1个月时自然杀伤细胞(CD3⁻CD56⁺)数量均恢复正常。两组的B淋巴细胞(CD19⁺)在最初4个月内计数均较低或检测不到,在8个月时达到正常范围。这些结果表明,在采用CD34⁺选择移植物的allo - PBT后的前6个月,CD4⁺、CD4⁺CD45RA⁺和TCRγδ⁺细胞数量显著低于未处理的allo - PBT后;这些差异在8个月时消失。相比之下,移植组之间在CD8⁺、CD19⁺和自然杀伤细胞的恢复方面没有差异。

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