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供受者IFN-γ基因＋874位点单核苷酸多态性对恶性血液病患者HLA全相合同胞供者异基因造血干细胞移植疗效的影响 被引量：2

Role of IFN-γ ＋ 874 genetic polymorphisms in allogeneic hematopoietic stem cell transplantation
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摘要 目的研究供受者IFN-γ基因＋874位点单核苷酸多态性（SNP）对恶性血液病患者HLA全相合同胞供者异基因造血干细胞移植（allo—HSCT）疗效的影响。方法收集80例接受HLA全相合同胞供者allo—HSCT的恶性血液病患者移植前外周血单个核细胞标本，采用序列特异性引物PCR（PCR—SSP）方法检测供受者IFN-γ＋874位点SNP，分析供受者不同基因型与移植疗效的相关性。结果供者为IFN-γ＋874A／A与非A／A基因型的两组患者恢复中性粒细胞绝对计数（ANC）〉0．5×10’／L的中位时间分别为15（11—27）d和18（12～30）d，差异有统计学意义（P=0．029）。供受者均为IFN-γ＋874A／A与＋874A／A基因型的两组患者恢复ANC〉0．5×10^9／L的中位时间分别为13（11—25）d和19（12—31）d，差异有统计学意义（P=0．019）。受者为IFN-γ＋874A／A与非A／A基因型的两组患者各有11例（20．0％）和1例（4％）发生Ⅱ-Ⅳ度急性移植物抗宿主病（aGVHD）（P=0．041），24例（43．6％）和4例（16．0％）发生巨细胞病毒（CMV）血症（P=0．032），预期5年无事件生存（EFS）率分别为（58．2±6．7）％和（84．0±7．3）％（P：0．032），5年移植相关死亡（TRM）率分别为（33．74-6．8）％和（12．04-6．5）％（P=0．050），差异均有统计学意义。供受者均为IFN-γ＋874A／A与均为非A／A纯合子型的两组患者各有10例（21．7％）和2例（5．9％）发生Ⅱ～Ⅳ度aGVHD（P=0．050）；21例（45．7％）和7例（20．6％）发生CMV血症（P=0．020），两组患者5年TRM率分别为（31．6±7．5）％和（13．6±6．5）％（P=0．048）；5年EFS率分别为（56．8±7．3）％和（79．4±6．9）％（P=0．037），差异均有统计学意义。结论在HLA全相合同胞供者allo—HSCT中，供者或供受者均为IFN-γ＋874A／A基因型的患者较非A／A基因型患者粒系植入时间显著提前，而受者或供受者均为A／A基因型较非A／A基因型患者移植后发生Ⅱ～Ⅳ度GVHD、CMV血症及TRM的风险显著增加，EFS率显著降低。 Objective To explore the impact of IFN-γ ＋ 874 polymorphisms on the outcome in HLA matched sibling HSCT. Methods We used PCR-sequenee-specific primer analysis （PCR-SSP） to analyze the polymorphisms of IFN-γ ＋ 874 T/A in 80 recipient and donor pairs from October 2005 to March 2008. Results Recipients having donors who possessed IFN-γ ＋ 874 A/A genotype had significantly earlier neutro- phil recovery compared with those having donors with non-A/A genotype （15 （11-27） days vs 18 （12 -30） days, P = 0. 029）. And IFN-γ ＋ 874 A/A in both recipients and donors further facilitated neutrophil recover- y compared with others （ 13 （ 11 - 25） days and 19 （ 12 - 31 ） days, P = 0. 019）. Besides, IFN-γ ＋ 874 A/A in recipients increased the probablity of grade H - 1V acute graft vursus disease （aGVHD） and cytomegalo-virus viraemia compared with IFN-γ ＋ 874 T/A or T/T genotype （20% vs 4% P = 0. 041, 43. 6% vs 16.0% P = 0.032） , which lead to increased 5-year transplant-related mortality （TRM） （ 33. 7% ＋ 6. 8% vs 12.0% ±6.5%, P =0.050） and decreased 5-year event free survival （EFS） E （58.2 ±6.7）% vs （84.0± 7.3 ） %, P = 0.032 ] compared with the latter. IFN-γ＋ 874 A/A in both recipients and donors also signifi- cantly increased the probablity of grade II - 1g aGVHD and cytomegalovirus viraernia compared with the other （21.7% vs 5.9% , P =0. 050; 45.7% vs 20.6%, P =0. 020）, which caused increased 5-year TRM [ （ 31.6 ± 7.5 ） % vs （ 13.6 ± 6.5 ） %, P = 0. 048 ] and decreased 5-year EFS [ （56.8 ± 7.3 ） % vs （79.4 ± 6.9） %, P = O. 037 ] compared with the other. Conclusion In HLA-matched sibling HSCT setting, the presences of IFN-γ＋ 874 T allele in recipients or in both recipients and donors significantly decreased the risk of grade Ⅱ～Ⅳ aGVHD and CMV infection and increased EFS. While IFN-γ＋ 874 A/A in donors or in both recipients and donors was associated with shorter duration to neutrophil recovery.
作者 蔡小矜 宋阿霞 王华 张平 张桂新 杨帆 魏嘉璘 马巧玲 阎嶂松 姜尔烈 黄勇 杨栋林 王玫 何祎 冯四洲 韩明哲
机构地区 中国医学科学院、北京协和医学院血液学研究所、血液病医院
出处 《中华血液学杂志》 CAS CSCD 北大核心 2012年第12期989-993,共5页 Chinese Journal of Hematology
基金 天津市自然科学基金（IOJCYBJC13100） 卫生部卫生行业科研专项基金（201202017） 重大血液病新药临床评价研究技术平台体系建设（2011ZX09302-007-4）
关键词 干扰素-Γ 多态性 单核苷酸 造血干细胞移植 预后 Intefferon-garnma Polymorphism, single nucleotide Hernatopoietic stern cell transplantation Graft vs host disease Prognosis
分类号 R55 [医药卫生—血液循环系统疾病]
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参考文献13

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同被引文献32

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  • 2CavetJ, DickinsonAM, NordenJ, et al. Interferon-gamma and interleukin-6 gene polymorphisms associate with graft-versushost disease in HLA-matched sibling bone marrow transplantation[J]. Blood, 2001,98(5):1594-1600.
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中华血液学杂志
2012年 第12期

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