The Clinical Characteristics Of Patients With CCUS、ICUS And MDS Based On Second-generation Sequencing

ObjectiveTo explore the clinical characteristics and relationship in patients with Idiopathic cytopenia of undetermined significance,Clonal cytopenia of unknown significance and Myelodysplastic syndromes.MethodsRetrospective analysis of 84 patients with ICUS,49 patients with CCUS and 139 patients with MDS admitted to 2100 patients who accept the second generation sequencing in the First Affiliated Hospital of Soochow University from July 2016 to July 2017.Collected all their datas,and summarized their clinical and laboratory characteristics.ResultsThere was significant difference in sex constituent ratio between ICUS group and MDS group(P=0.001),MDS group was more common in males,but there was no significant difference between CCUS group and MDS group(P<0.01).The median age of ICUS group,CCUS group and MDS group was 47 years old,54 years old and 49 years old,and there was no significant difference(P=0.308).The neutrophil count and hemoglobin level in patients with MDS were significantly lower than those in ICUS group and CCUS group(P<0.001),but there was no significant difference in platelet count,reticulocyte count and lactate dehydrogenase among the three groups.The level of WT1 in MDS group was higher than that in ICUS group and CCUS group(P<0.001).There was no significant difference between CCUS group and ICUS group.The decrease of primary lineage was more common in ICUS group,and the decrease of two lineage was more common in MDS group(P<0.001).The mutations with higher incidence in CCUS group were DNMT3 A(8 cases),TET2(8 cases),NOTCH1(6 cases)and BCOR(6 cases in),MDS group).The most common mutations were ASXL1(31 cases),U2AF1(29 cases),RUNX1(18 cases),SETBP1(12 cases)and TET2(11 cases)in MDS group.The frequency of U2AF1 gene mutation was higher in MDS group than that in CCUS group(P=0.018).There was no significant difference in other common genes between these two groups.One gene mutation was more common in CCUS group and more than 3 gene mutations in MDS group(P<0.001).The median follow-up time of patients in ICUS group and CCUS group was 35.5 months and 35 months respectively.During the follow-up,4 cases in ICUS group progressed to AA,1 case progressed to MDS.In CCUS group,1 patient progressed to AA,1 progressed to AML and 1 case to gastric malignant tumor.The mortality rate in the ICUS group was 1.2%,2.0%in the CCUS group and 31.7%in the MDS group.The hemoglobin level in progressive group was lower than that in non-progressive group.Patients with NRAS mutation had significantly shorter OS(P=0.02)and PFS(P=0.0013)compared with those without gene mutations.The OS of the patients with TET2 and TP53 gene mutations was shorter than that of the patients without the mutations(P=0.018,P=0.03),while the PFS of the patients with DNMT3A and ASXL1 gene mutations was shorter than that of the patients without mutations(P=0.037,P=0.028).TET2,TP53 and NRAS gene mutations were independent risk factors for the prognosis of patients with MDS.ConclusionsThe sex constituent ratio and age of onset of CCUS patients were similar to those of MDS patients,their were more common in male patients.Patients with CCUS and ICUS had higher levels of neutrophils,hemoglobin and WT1 than patients with MDS.Patients with disease progression in ICUS group and CCUS group had higher hemoglobin levels.The mortality rate in MDS group was higher than that in ICUS and CCUS patients.The number of gene mutations in MDS group was more than that in CCUS group,suggesting that gene mutation may be a factor affecting the transformation of CCUS disease.Therefore,in clinical work,attention must be paid to the hematological follow-up of patients with ICUS and CCUS,and patients with CCUS should also be combined with the results of gene sequencing in order to achieve the final diagnosis and predict the progress of the disease.Further study on a large scale is still recommended.