胸骨骨髓细胞形态学在染色体核型正常获得性低增生性骨髓衰竭综合征且患者中的诊断价值

Sternal bone marrow cell morphology evaluation utility for diagnostic categorization in patients with acquired hypocellular bone marrow failure syndromes

目的探讨胸骨骨髓细胞形态学在基于髂骨穿刺骨髓细胞形态学和骨髓活检组织切片细胞形态学表现为染色体核型正常获得性低增生性骨髓衰竭综合征(BMFS)患者的诊断价值。方法回顾性分析2014年6月至2019年1月中国医学科学院血液病医院(中国医学科学院血液学研究所)初诊的194例获得性低增生性BMFS患者的临床资料,结合胸骨骨髓细胞形态学结果重新诊断分型,分析各诊断分型患者的临床特征及预后差异。通过Logistic回归进行多因素分析,建立推荐该类患者进行胸骨骨髓细胞形态学分析的积分系统。结果194例染色体核型正常的获得性低增生性BMFS患者,基于髂骨骨髓检查结果初步诊断为再生障碍性贫血(AA)152例,意义未明的特发性血细胞减少症(ICUS)29例,意义未明的克隆性血细胞减少症(CCUS)13例,结合胸骨骨髓细胞形态学结果后分别有42.8%(65/152)、24.1%(7/29)和30.8%(4/13)患者最终诊断为低增生型骨髓增生异常综合征(hypo-MDS)。胸骨骨髓检查结果最终诊断为AA与hypo-MDS患者总生存率差异有统计学意义(P=0.005)。对结合胸骨骨髓检查结果最终诊断为AA和hypo-MDS两组患者临床特征、外周血血细胞参数和髂骨骨髓实验室特征进行单因素及多因素分析结果表明,年龄>60岁(OR=6.647,95%CI 1.954~22.611,P=0.002,积2分)、NALP阳性指数≤160(OR=2.654,95%CI 1.214~5.804,P=0.014,积1分)、髂骨骨髓流式红系表型异常(OR=6.200,95%CI 1.165~32.988,P=0.032,积2分)及有DAT(DNMT3A、ASXL1、TET2)基因突变(OR=4.809,95%CI 1.587~14.572,P=0.005,积1分)均为影响染色体核型正常的获得性低增生性BMFS患者结合胸骨骨髓细胞形态学分析后诊断为hypo-MDS的独立预测因素。使用赤池信息准则(AIC)对模型进行预测效能评估,AIC=186.1。当积分≥2分时诊断为hypo-MDS的特异性为91.7%,阳性预测值为80.6%。结论染色体核型正常的获得性低增生性BMFS患者,仅通过髂骨骨髓细胞形态学和骨髓活检组织病理学可能产生误诊。我们提出一项积分系统,当积分≥2分时强烈建议该类患者进行胸骨骨髓细胞形态学检查有助于明确诊断分型。

Objective Diagnostic value assessment of sternal bone marrow cell morphology in patients with acquired hypocellular bone marrow failure syndromes(BMFS)characterized by normal cytogenetics.Methods A total of 194 eligible patients with an acquired hypocellular BMFS pre-sternum diagnosis in Institute of Hematology and Blood Diseases Hospital,Chinese Academy of Medical Science&Peking Union Medical College from June 2014 to January 2019 were reviewed.Sternal bone marrow evaluation was performed,and a post-sternum diagnosis was made.Clinical characteristics and overall survival(OS)were then compared among patients with different post-sternum diagnosis.Binary logistic regression was used to develop a predictive scoring system.Results In 152 patients with pre-sternum AA diagnosis,29 patients with a pre-sternum idiopathic cytopenia of undetermined significance(ICUS)diagnosis,and 13 patients with a pre-sternum clonal cytopenia of undetermined significance(CCUS)diagnosis,sternal bone marrow evaluation resulted in a change of diagnosis to hypocellular myelodysplastic syndrome(hypo-MDS)in 42.8%(65/152),24.1%(7/29),and 30.8%(4/13),respectively.Patients with a post-sternum hypo-MDS diagnosis showed a significant difference in OS compared with patients with a post-sternum AA diagnosis(P=0.005).Patients with ICUS/CCUS showed no difference in OS compared with AA and hypo-MDS(P=0.095 and P=0.480,respectively).A 4-item predictive scoring system to identify hypocellular BMFS patients that need sternal bone marrow evaluation was developed,including age>60 years old(OR=6.647,95%CI 1.954-22.611,P=0.002,2 points),neutrophil alkaline phosphatase score≤160(OR=2.654,95%CI 1.214-5.804,P=0.014,1 point),abnormal erythroid markers evaluated by flow cytometry on iliac bone marrow(OR=6.200,95%CI 1.165-32.988,P=0.032,2 points),and DAT(DNMT3A,ASXL1,TET2)genes mutation(OR=4.809,95%CI 1.587-14.572,P=0.005,1 point).The Akaike information criterin(AIC)was 186.1.Conclusion Patients with a pre-sternum acquired hypocellular BMFS diagnosis characterized by normal cytogenetics may not reach accurate diagnostic categorization without sternal bone marrow cell morphology evaluation,which could be considered a diagnostic tool for this patient population.A predictive scoring system was developed,and when the total score is≥2 points,sternal bone marrow evaluation should be performed for accurate diagnostic categorization that is critical to optimal patient care.