Objective: To analyze clonal evolution and clinical significance of trisomy 8 in patients with acquired bone marrow failure. Methods: The clinical data of 63 patients with acquired bone marrow failure accompanied with isolated trisomy 8 (+8) from June 2011 to September 2018 were analyzed retrospectively, the clonal evolution patterns and relationship with immmunosuppressive therapy were summarized. Results: Totally 24 male and 39 female patients were enrolled, including 39 patients with aplastic anemia (AA) and 24 patients with relatively low-risk myelodysplastic syndrome (MDS) . Mean size of+8 clone in MDS patients[65% (15%-100%) ]was higher than that of AA patients[25% (4.8%-100%) , z=3.48, P=0.001]. The patients were was divided into three groups (<30%, 30%-<50%,and ≥50%) according to the proportion of+8 clone. There was significant difference among the three groups between AA[<30%:55.6% (20/36) ; 30-50%: 22.2% (8/36) ; ≥50%22.2% (8/36) ]and MDS patients[<30%:19.0% (4/21) ; 30%-<50%:19.0% (4/21) ; ≥50%61.9% (13/21) ] (P=0.007) . The proportion of AA patients with+8 clone <30% was significantly higher than that of MDS patients (P=0.002) ; and the proportion of AA patients with+8 clone ≥50%was significantly lower than that of MDS patients (P=0.002) . The median age of AA and MDS patients was respectively 28 (7-61) years old and 48.5 (16-72) years old. Moreover, there was no correlation between age and+8 clone size in AA or MDS (r(s)=0.109, P=0.125; r(s)=-0.022, P=0.924, respectively) . There was statistical difference in total iron binding capacity, transferrin and erythropoietin between high and low clone group of AA patients (P=0.016, P=0.046, P=0.012, respectively) , but no significant difference in MDS patients. The immunosuppressive therapy (IST) efficacy of AA and MDS patients was respectively 66.7% and 43.8% (P=0.125) . Comparing with initial clone size (27.3%) , the +8 clone size (45%) of AA patients was increased 1-2 year after IST, but no statistical difference (z=0.83, P=0.272) . Consistently, there was no significant change between initial clone size (72.5%) and 1-2 year clone size (70.5%) after IST in MDS patients. There was no significant difference in IST efficient rate between +8 clone size expansion and decline group of in AA patients at 0.5-<1, 1-2 and>2 years after IST. We found four dynamic evolution patterns of +8 clone, which were clone persistence (45%) , clone disappearance (30%) , clone emergence (10%) and clone recurrence (15%) . Conclusions: AA patients had a low clone burden, while MDS patients had a high burden of +8 clone. The +8 clone of AA patients didn't significantly expanded after IST, and the changes of +8 clone also had no effect on IST response.
目的： 分析获得性骨髓衰竭患者8号染色三体（+8）的克隆演变及其临床意义。 方法： 回顾性分析2011年6月至2018年9月63例伴单纯+8染色体的获得性骨髓衰竭患者临床资料，总结克隆演变模式及其与免疫抑制治疗（IST）疗效的关系。 结果： 63例患者中AA 39例，相对低危MDS 24例，男24例，女39例。MDS患者治疗前+8克隆负荷大于AA患者[65%（15%~100%）对25%（4.8%~100%），z=3.48，P=0.001]。AA及MDS患者+8克隆大小<30%、30%~<50%、≥50%3组间的比例差异有统计学意义[AA分别为55.6%（20/36）、22.2%（8/36）、22.2%（8/36），MDS分别为19.0%（4/21）、19.0%（4/21）、61.9%（13/21），P=0.007]；两两比较显示+8克隆<30%的AA患者明显多于MDS患者（P=0.002），+8克隆≥50%的AA患者明显少于MDS患者（P=0.002）。AA与MDS患者中位年龄分别为28（7~61）岁、48.5（16~72）岁，且两者+8克隆负荷与年龄均无显著相关性（r(s)分别为0.109、－0.022，P值分别为0.528、0.924）。异常克隆负荷≥50%定义为大克隆，<50%为小克隆，AA患者大小克隆两组间总铁结合力、转铁蛋白、红细胞生成素差异有统计学意义（P值分别为0.016、0.046及0.012）。AA与MDS患者IST有效率分别为66.7%（22/33）、43.8%（7/16）（P=0.215）。AA患者治疗后1~2年的+8克隆负荷[45%（5%~85%）]较初诊时[27.3%（4.8%~100.0%）]增加，但差异无统计学意义（z=0.83，P=0.272）；MDS患者治疗后1~2年的克隆负荷为70.5%（10%~100%），相比初诊时[72.5%（25%~100%）]略减少。IST后0.5~<1年、1~2年、>2年，AA+8克隆减少组与增加组的IST有效例数无明显变化。AA+8克隆有4种动态演变模式，分别为克隆持续（45%）、克隆消失（30%）、克隆新发（10%）以及克隆反复（15%）。 结论： AA患者+8克隆低负荷，而MDS患者+8克隆高负荷；AA患者的+8克隆在IST后无明显扩增，+8克隆的增减对IST疗效无明显影响。.
Keywords: Acquired bone marrow failure; Clonal evolution; Immunosuppressive therapy; Trisomy 8.