Zhou L W, Shi J, Huang Z D, Nie N, Shao Y Q, Li X X, Ge M L, Zhang J, Jin P, Huang J B, Zheng Y Z
Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China; State Key Laboratory of Experimental Hematology, Tianjin 300020, China.
Zhonghua Xue Ye Xue Za Zhi. 2019 Jun 14;40(6):507-511. doi: 10.3760/cma.j.issn.0253-2727.2019.06.011.
To analyze clonal evolution and clinical significance of trisomy 8 in patients with acquired bone marrow failure. 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. 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%) , =3.48, =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) ] (=0.007) . The proportion of AA patients with+8 clone <30% was significantly higher than that of MDS patients (=0.002) ; and the proportion of AA patients with+8 clone ≥50%was significantly lower than that of MDS patients (=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 ((s)=0.109, =0.125; (s)=-0.022, =0.924, respectively) . There was statistical difference in total iron binding capacity, transferrin and erythropoietin between high and low clone group of AA patients (=0.016, =0.046, =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% (=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 (=0.83, =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%) . 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.
分析获得性骨髓衰竭患者8号染色体三体的克隆演变及临床意义。回顾性分析2011年6月至2018年9月63例伴有孤立8号染色体三体（+8）的获得性骨髓衰竭患者的临床资料，总结其克隆演变模式及与免疫抑制治疗的关系。共纳入24例男性和39例女性患者，其中再生障碍性贫血（AA）患者39例，低危骨髓增生异常综合征（MDS）患者24例。MDS患者中+8克隆的平均比例[65%（15%-100%）]高于AA患者[25%（4.8%-100%），Z=3.48，P=0.001]。根据+8克隆比例将患者分为三组（<30%、30%-<50%和≥50%）。AA患者[<30%：55.6%（20/36）；30%-50%：22.2%（8/36）；≥50%：22.2%（8/36）]和MDS患者[<30%：19.0%（4/21）；30%-<50%：19.0%（4/21）；≥50%：61.9%（13/21）]三组间差异有统计学意义（P=0.007）。+8克隆<30%的AA患者比例显著高于MDS患者（P=0.002）；+8克隆≥50%的AA患者比例显著低于MDS患者（P=0.002）。AA和MDS患者的中位年龄分别为28（7-61）岁和48.5（16-72）岁。此外，AA或MDS患者的年龄与+8克隆大小均无相关性（r（s）=0.109，P=0.125；r（s）=-0.022，P=0.924）。AA患者高、低克隆组间总铁结合力、转铁蛋白和促红细胞生成素差异有统计学意义（分别为P=0.016、P=0.046、P=0.012），而MDS患者无显著差异。AA和MDS患者免疫抑制治疗（IST）的有效率分别为66.7%和43.8%（P=0.125）。与初始克隆比例（27.3%）相比，AA患者IST治疗1-2年后+8克隆比例（45%）升高，但差异无统计学意义（P=0.83，P=0.272）。同样，MDS患者IST治疗后初始克隆比例（72.5%）与1-2年克隆比例（70.5%）间无显著变化。AA患者IST治疗后0.5-<1年、1-2年和>2年时，+8克隆比例升高组与降低组的IST有效率无显著差异。我们发现+8克隆有四种动态演变模式，即克隆持续存在（45%）、克隆消失（30%）、克隆出现（10%）和克隆复发（15%）。AA患者克隆负荷低，而MDS患者+8克隆负荷高。AA患者IST治疗后+8克隆未显著扩增，+8克隆的变化对IST反应也无影响。
