Clinical features of essential thrombocythemia patients with a minor increase in reticulin fibers of bone marrow
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摘要: 目的 探索伴随骨髓网状纤维增多原发性血小板增多症(essential thrombocythemia，ET)患者的危险因素。方法 将58例ET患者根据是否伴有轻度骨髓网状纤维增多(1级)分为增多组(29例)和无增多组(29例)，比较2组患者间基线资料、基因突变、血常规、生化、骨髓细胞学、骨髓活检等指标差异，进一步多因素回归分析影响ET患者伴随轻度骨髓网状纤维增多的独立危险因素。结果 与无增多组比较，增多组患者的 TET2 突变频率(30.77% vs 8.33%，P=0.048)、血小板计数(PLT)[(820.93±242.95)×109/L vs (673.93±174.00)×109/L，P=0.01]、乳酸脱氢酶[(285.63±97.60) U/L vs (213.46±45.14) U/L，P=0.02]、造血容量[(62.00±15.75)% vs (53.20±12.82)%，P=0.04]、粒系细胞占比[(63.64±8.61)% vs (57.70±8.80)%，P=0.02]、粒红细胞比[(4.01±2.02) vs (2.88±1.58)，P=0.04]均明显增多，原始细胞占比[(0.46±0.67)% vs (1.52±1.03)%，P < 0.01]明显减少；2组患者 JAK2 突变频率差异无统计学意义(P>0.05)。对P < 0.05的因素进行logistic回归分析发现， TET2 突变、PLT>800×109/L是ET患者网状纤维增多的独立危险因素(P < 0.05)。结论 TET2 突变、PLT>800×109/L是ET患者发生网状纤维增多的独立危险因素。Abstract: Objective To investigate the clinical features of essential thrombocythemia(ET) patients with minor increases in reticulin fibers of bone marrow.Methods A total of 58 ET patients were collected and divided into an increase group(n=29) and a non-increase group(n=29) according to whether they had a minor increase(grade 1) in reticulin fibers of bone marrow. Then, the differences in baseline data, gene mutation, peripheral blood cell count, biochemistry, bone marrow cytology, bone marrow biopsy and other indicators between the two groups were compared respectively, and the independent risk factors of ET patients with bone marrow fibrotic hyperplasia were further analyzed by logistic regression.Results Compared with the non-increase group, the proportion of TET2 mutation(30.77% vs 8.33%, P=0.048), PLT([820.93±242.95]×109/L vs [673.93±174.00]×109/L, P=0.01), LDH([285.63±97.60]U/L vs [213.46±45.14]U/L, P=0.02), hematopoietic volume([62.00±15.75]% vs [53.20±12.82]%, P=0.04), the proportion of granulocyte([63.64±8.61]% vs [57.70±8.80]%, P=0.02), granulocyte to erythrocyte ratio([4.01±2.02] vs [2.88 ±1.58], P=0.04) in the increasing group significantly increased, while the proportion of blasts([0.46±0.67]% vs [1.52±1.03]%, P < 0.01) significantly decreased. There was no significant difference in the proportion of patients with JAK2 mutation at different frequencies between the two groups(P>0.05). Logistic regression analysis of factors with P < 0.05 showed that the TET2 mutation and PLT>800×109/L were independent risk factors of ET patients with minor increases in reticulin fibers of bone marrow(P < 0.05).Conclusion TET2 mutation and PLT>800×109/L are independent risk factors of ET patients with minor increases in reticulin fibers of bone marrow.
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表 1 2组患者基因突变情况比较
例(%) 驱动基因突变 增多组(n=29) 无增多组(n=29) P JAK2 17(58.62) 14(48.28) 0.43 CALR 11(37.93) 8(27.59) 0.40 MPL 0 2(6.90) 三阴性 1(3.45) 5(17.24) 0.19 
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表 2 2组患者不同非驱动基因突变频率比较
例(%) 非驱动基因突变 增多组(n=26) 无增多组(n=24) P TET2 8(30.77) 2(8.33) 0.048 ASXL1 2(7.69) 2(8.33) 0.930 DNM3TA 1(3.85) 2(8.33) 0.500
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表 3 2组患者血细胞计数比较
X±S 检测项目 增多组(n=29) 无增多组(n=29) P WBC/(109/L) 7.57±1.85 6.89±1.68 0.18 HGB/(g/L) 132.65±12.19 135.55±10.27 0.41 PLT/(109/L) 820.93±242.95 673.93±174.00 0.01 HCT/% 38.28±9.31 40.86±3.22 0.22 PCT/% 0.74±0.21 0.64±0.15 < 0.05 N/(109/L) 5.28±1.76 5.22±2.12 0.91 L/(109/L) 1.91±0.56 1.85±0.72 0.75 N/L 3.15±1.55 3.12±1.40 0.92 MONO/(109/L) 0.40±0.16 0.44±0.19 0.43 EOS/(109/L) 0.14±0.10 0.14±0.08 0.95 BAS/(109/L) 0.07±0.05 0.07±0.04 0.84 MPV/% 9.46±1.03 9.81±0.90 0.19 PDW/fL 11.92±2.81 10.98±1.84 0.15 P-LCR/% 22.31±5.20 23.46±5.33 0.45
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表 4 2组患者生化指标比较
X±S 检测项目 增多组(n=29) 无增多组(n=29) P ALT/(U/L) 30.00±15.12 30.06±15.99 0.99 AST/(U/L) 25.37±10.51 24.61±7.55 0.79 LDH/(U/L) 285.63±97.60 213.46±45.14 0.02 HBD/(U/L) 179.99±65.25 142.24±34.29 0.13 GGT/(U/L) 42.74±38.92 29.30±17.80 0.18 ALP/(U/L) 65.29±34.27 73.96±23.99 0.39 GLU/(mmol/L) 4.98±1.10 5.15±0.58 0.58 UREA/(μmol/L) 4.42±1.49 4.86±1.89 0.45 CRE/(μmol/L) 68.16±16.99 66.45±12.27 0.72 UA/(μmol/L) 328.94±87.29 344.05±85.87 0.61 TG/(mmol/L) 1.40±0.69 1.49±0.86 0.78
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表 5 2组患者骨髓特征比较
检测项目 增多组(n=29) 无增多组(n=29) P 骨髓增生/例(%) 0.11 Ⅱ 5(17.24) 3(10.34) Ⅲ 17(58.62) 20(68.97) Ⅳ 7(24.14) 6(20.69) 粒系细胞占比/% 63.64±8.61 57.70±8.80 0.02 红系细胞占比/% 20.07±13.36 23.63±7.95 0.27 巨核系细胞/个 104.57±127.63 123.50±130.28 0.42 淋巴系细胞占比/% 15.74±5.96 15.85±6.54 0.95 粒红细胞比 4.01±2.02 2.88±1.58 0.04 淋红细胞比 0.99±0.68 0.75±0.39 0.15 原始细胞占比/% 0.46±0.67 1.52±1.03 < 0.01 造血容量/% 62.00±15.75 53.20±12.82 0.04
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表 6 自变量赋值方法
自变量 赋值方法 TET2 突变=1，未突变=0 LDH >220 U/L=1，≤220 U/L=0 粒细胞比例 >60%=1，≤60%=0 原始细胞比例 < 1%=1，≥1=0 造血容积 >60%=1，≤60=0 PLT >800×109/L=1，≤800×109/L=0
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表 7 ET患者网状纤维增多危险因素的logistic回归分析
变量 B SE Wald P Exp(B) 上限 下限 OR PLT>800×109/L 1.379 0.658 4.398 0.036 3.971 1.094 14.410 14.591 TET2突变 1.763 0.876 4.045 0.044 5.827 1.046 32.467 14.727
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