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

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%). CONCLUSION: 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.