Immunologic effects of prophylactic donor lymphocyte infusion after allogeneic marrow transplantation for multiple myeloma
Immunologic effects of prophylactic donor lymphocyte infusion after allogeneic marrow transplantation for multiple myeloma
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DOI：
10.1182/blood.v99.12.4610
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发表时间：
2002-06-15
期刊：
影响因子：
20.3
通讯作者：
Ritz, J
中科院分区：
文献类型：
--
作者：
Bellucci, R;Alyea, EP;Ritz, J
骨髓移植（BMT）后T细胞免疫的重建通常被延迟，导致免疫缺陷的延长。供体淋巴细胞输注（DLI）已被用于增强BMT后的移植物抗白血病活性，但DLI对免疫重建的影响尚未确定。我们研究了9例多发性骨髓瘤患者，他们接受骨髓成白细胞治疗和T细胞去除的异基因骨髓移植，6个月后输注来自同一供体的淋巴细胞。DLI由3 × 10（7）个CD 4（+）供体T细胞/kg组成，所述供体T细胞在体外去除CD 8（+）细胞后获得。在BMT后的前6个月和DLI后1年研究外周血淋巴细胞的细胞表面表型、T细胞受体（TCR）V β库、TCR重排切除环（TRECs）和造血嵌合体。这些研究还在7例接受类似清髓性治疗和BMT但未接受DLI的患者中进行。两组的T细胞和自然杀伤细胞表型重建相似，但接受CD 4（+）DLI的患者出现了CD 20（+）B细胞数量增加。BMT后3个月和6个月TCR V β库复杂性降低，但接受DLI的患者改善更快（P = .01）。CD 4（+）DLI还与CD 3（+）T细胞中TRECs数量的增加（P <0.001）和向完全供体造血的转化（P = 0.05）相关。这些结果提供了证据，证明在BMT后6个月预防性输注CD 4（+）供体淋巴细胞可增强供体T细胞的重建和向供体造血的转化，以及促进抗肿瘤免疫。(C)2002年，美国血液学会。
Reconstitution of T-cell immunity after bone marrow transplantation (BMT) is often delayed, resulting in a prolonged period of immunodeficiency. Donor lymphocyte infusion (DLI) has been used to enhance graft-versus-leukemia activity after BMT, but the effects of DLI on immune reconstitution have not been established. We studied 9 patients with multiple myeloma who received myeloalblative therapy and T-cell-depleted allogeneic BMT followed 6 months later by infusion of lymphocytes from the same donor. DLI consisted of 3 X 10(7) CD4(+) donor T cells per kilogram obtained after in vitro depletion of CD8(+) cells. Cell surface phenotype of peripheral lymphocytes, T-cell receptor (TCR) Vbeta repertoire, TCR rearrangement excision circles (TRECs), and hematopoietic chimerism were studied in the first 6 months after BMT and for I year after DLI. These studies were also performed in 7 patients who received similar myeloablative therapy and BMT but without DLI. Phenotypic reconstitution of T and natural killer cells was similar in both groups, but patients who received CD4(+) DLI developed increased numbers of CD20(+) B cells. TCR Vbeta repertoire complexity was decreased at 3 and 6 months after BMT but Improved more rapidly in patients who received DLI (P = .01). CD4(+) DLI was also associated with increased numbers of TRECs In CD3(+) T cells (P < .001) and with conversion to complete donor hematopoiesis (P = .05). These results provide evidence that prophylactic infusion of CD4(+) donor lymphocytes 6 months after BMT enhances reconstitution of donor T cells and conversion to donor hematopoiesis as well as promoting antitumor Immunity. (C) 2002 by The American Society of Hematology.