急性白血病患者HLA不全相合非清髓造血干细胞移植后淋巴细胞亚群变化分析  

Changes of Lymphocyte Subsets in Acute Leukemia Patients after HLA-mismatched Nonmyeloablative Hematopoietic Stem Cell Transplantation

作　　者：胡锴勋[1] 郭梅[1] 余长林[1] 王丹红[1] 孙琪云[1] 乔建辉[1] 刘广贤[1] 刘铁强[1] 艾辉胜[1] 

机构地区：[1]军事医学科学院附属医院血液科,北京100071

出　　处：《中国实验血液学杂志》2009年第6期1527-1531,共5页Journal of Experimental Hematology

基　　金：国家"863"资助(2002AA216081)

摘　　要：本研究观察并比较急性淋巴细胞白血病及急性髓系白血病患者经HLA不全相合非清髓造血干细胞移植(NST)后免疫重建及其与感染和移植物抗宿主病(GVHD)的关系。6名急性淋巴细胞白血病(ALL),4名急性髓系白血病(AML)患者有HLA不全相合亲缘供者,接受以氟达拉滨,ATG,阿糖胞苷,环磷酰胺,TBI2Gy为主的非清髓预处理方案,移植前后给予环孢霉素A或他克莫司联合霉酚酸酯防治GVHD。采用流式细胞术分别于移植前化疗缓解期,移植后监测患者体内的总T细胞、辅助/诱导T细胞、抑制/杀伤T细胞、γ/δT细胞、CD4/CD8比值,B细胞、NK细胞、NKT细胞、调节T细胞、活化T细胞、原始T细胞、记忆T细胞移植后变化规律,分析各免疫功能细胞与移植后感染及急、慢性GVHD的关系;比较ALL与AML免疫系统恢复差别。结果表明,移植后患者各淋巴细胞量恢复有各自规律,发生GVHD患者各淋巴细胞亚群数量较高,而移植后1个月γ/δT细胞、调节T细胞、NK细胞量较低。移植后2-3月时CD4/CD8、B细胞、NK细胞、原始T细胞较低。6-8个月时B细胞,原始T细胞,NK细胞较低。移植后早期发生感染患者总T细胞及各淋巴亚群恢复较慢,NK,NKT细胞数恢复较快,移植后3个月出现感染的患者,其B细胞及原始T细胞量恢复较快。ALL与AML患者淋巴细胞恢复无差异。结论:不全相合NST后各淋巴细胞亚群分析可间接反映患者胸腺功能恢复状态,NK、B细胞、原始T细胞的变化对区分和监测GVHD及感染有重要意义。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 （Fin）, 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, γ/δg 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 γ/δg T cells, regulatory T cells, NK cells, the counts of B cells, NK ceils, 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 monthes and 6 -8 monthes 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 monthes 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 indirect

关 键 词：造血干细胞移植 急性白血病 HLA不全相合 移植物抗宿主病 T细胞亚群 

分 类 号：R733.71[医药卫生—肿瘤] R457.7[医药卫生—临床医学]