Hu Kai-Xun, Guo Mei, Yu Chang-Lin, Wang Dan-Hong, Sun Qi-Yun, Qiao Jian-Hui, Liu Guang-Xian, Liu Tie-Qiang, Ai Hui-Sheng
Department of Hematology, Affiliated Hospital, Academy of Military Medical Sciences, Beijing 10071, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Dec;17(6):1527-31.
This study was purposed to investigate the reconstitution of immune system in patients with acute lymphocyte leukemia (ALL) or acute myeloid leukemia (AML) after HLA-mismatched nonmyeloablative hematopoietic stem cell transplantation (NHSCT) and its relation with infection and GVHD. 6 ALL and 4 AML patients having HLA-mismatched related donors received the nonmyeloablative precondition regimen composed of fludarabine (Fln), ATG, Ara-C, CTX and total body irradiation (TBI) in dose 2 Gy. The GVHD was prevented and treated by CsA, anti-CD25 antibody and mycophenolic mofetil (MMF) before and after transplantation. The flow cytometry was used to detect the changes of total T cells, help/inducer T cells, suppressor/killer T cells, gamma/delta T cells, B cells, NK cells, NKT cells, regulatory T cells, activated T cells, naive T cells, memory T cells and ratio of CD4/CD8 in patients with remission resulting from chemotherapy before transplantation, and analyse the relation of immunofunctional cells to infection and GVHD after transplantation, compare the difference in recovery of immune system of ALL and AML patients. The results showed that the recovery of total lymphocytes and lymphocyte subsets displayed one's own regular pattern. As compared with patients without GVHD, the counts of lymphocyte subsets in patients with GVHD was higher, while the counts of gamma/delta T cells, regulatory T cells, NK cells, the counts of B cells, NK cells, naive cells and CD4/CD8 ratio as well as the counts of B cells, naive T cells and NK cells were lower at 1 month, 2 - 3 months and 6 - 8 months after transplantation respectively. The total T cells and subsets recovered slowly, but NK cells and NKT cells recovered rapidly in patients with infection at early period after transplantation, the B cells and naive B cells recovered rapidly at 3 months after transplantation. There was no difference in lymphocyte recovery between ALL and AML patients. It is concluded that the analysis of each lymphocyte subsets may indirectly show the recovery of thymus function in patients, the changes of NK cells, B cells and naive T cells have an important significance for identifying and forecasting the GVHD and infection.
本研究旨在探讨急性淋巴细胞白血病(ALL)或急性髓系白血病(AML)患者在HLA配型不合的非清髓性造血干细胞移植(NHSCT)后免疫系统的重建情况及其与感染和移植物抗宿主病(GVHD)的关系。6例ALL患者和4例AML患者接受了HLA配型不合的相关供者移植,采用由氟达拉滨(Fln)、抗胸腺细胞球蛋白(ATG)、阿糖胞苷(Ara-C)、环磷酰胺(CTX)及2 Gy全身照射(TBI)组成的非清髓性预处理方案。移植前后采用环孢素A(CsA)、抗CD25抗体及霉酚酸酯(MMF)预防和治疗GVHD。采用流式细胞术检测移植前化疗缓解患者的总T细胞、辅助/诱导性T细胞、抑制/杀伤性T细胞、γ/δT细胞、B细胞、自然杀伤细胞(NK细胞)、自然杀伤T细胞(NKT细胞)、调节性T细胞、活化T细胞、初始T细胞、记忆T细胞及CD4/CD8比值的变化,并分析移植后免疫功能细胞与感染和GVHD的关系,比较ALL和AML患者免疫系统恢复的差异。结果显示,总淋巴细胞及淋巴细胞亚群的恢复呈现各自的规律。与未发生GVHD的患者相比,发生GVHD患者的淋巴细胞亚群计数较高,而移植后1个月、2 - 3个月及6 - 8个月时,γ/δT细胞、调节性T细胞、NK细胞、B细胞、NK细胞、初始细胞及CD4/CD8比值以及B细胞、初始T细胞及NK细胞的计数分别较低。总T细胞及其亚群恢复缓慢,但移植后早期发生感染患者的NK细胞和NKT细胞恢复迅速,B细胞和初始B细胞在移植后3个月恢复迅速。ALL和AML患者淋巴细胞恢复情况无差异。结论:对各淋巴细胞亚群的分析可间接反映患者胸腺功能的恢复情况,NK细胞、B细胞及初始T细胞的变化对识别和预测GVHD及感染具有重要意义。