再生障碍性贫血免疫抑制治疗后阵发性睡眠性血红蛋白尿症克隆的演变及临床意义

目的 探索再生障碍性贫血(AA)免疫抑制治疗(IST)后阵发性睡眠性血红蛋白尿症(PNH)克隆变化情况及其临床意义.方法 将2008年1月至2012年2月收治的186例AA患者纳入本研究,其中55例重型AA(SAA)予抗胸腺细胞球蛋白(ATG)联合环孢素A(CsA)治疗,131例非重型AA(NSAA)予CsA治疗.治疗前所有患者进行PNH克隆筛查,治疗后进行随访.中位随访时间22(18 ～76)个月.结果 SAA组10例(18.9％)患者出现PNH克隆,NSAA组9例(7.4％)出现PNH克隆,前者出现PNH克隆比例高于后者(t=5.041,P=0.025),治疗后SAA组在6、12、18、＞24个月时PNH克隆规模大于NSAA组(13.38％比5.67％、14.88％比5.31％、20.00％比5.47％、18.85％比9.08％,P值均＜0.05).PNH克隆对2种IST方案疗效影响的差异无统计学意义.结论 AA患者予ATG联合CsA或CsA治疗后,均可出现PNH克隆,SAA患者ATG治疗后更明显.IST前后伴PNH克隆不影响IST疗效.

The variation and clinical significance of paroxysmal nocturnal hemoglobinuria clone in patients with aplastic anemia before and after immunosuppressive therapy

Objective To evaluate the evolution of paroxysmal nocturnal hemoglobinuria (PNH) clone and its clinical significance before and after immunosuppressive therapy (IST) in patients with aplastic anemia (AA).Methods A total of 186 patients diagnosed as AA were enrolled in this study. Among them, 55 patients were diagnosed as severe AA (SAA) and treated with cyclosporine (CsA) plus anti-thymocyteglobulin (ATG), 131 were diagnosed as non SAA (NSAA) and treated with CsA alone. All patients were screened for PNH clone by flow cytometry before treatment and followed up for 18-76 months, with a median time of 22 months.Results Positive PNH clones were detected in 10 SAA (18.9%) patients, significantly more than that of NSAA group [9 patients (7.4%), t=5.041,P=0.025]. The proportions of PNH clones in SAA group at 6, 12, 24 and ＞24 months were 13.38%, 14.88%, 20.00% and 18.85%, respectively, also significantly higher than those of NSAA patients (5.67%, 5.31%, 5.47% and 9.08%, all P values ＜0.05). Clinical response rates were comparable in both ATG+CsA or CsA alone groups no matter PNH clone was positive or negative.Conclusions PNH clone are detectable in AA patients either treated with ATG plus CsA or CsA alone, and more significant by ATG plus CsA. Whether PNH clone occurres before or after IST does not affect the therapeutic efficacy.