The diagnostic and prognostic value of targeted next-generation sequencing in myelodysplastic syndrome

Objective To explore the diagnostic and prognostic values of targeted next-generation sequencing (NGS) for patients with myelodysplastic syndrome (MDS). Methods A total of 205 cytopenias patients with suspected MDS who were admitted to Department of Hematology, the Affiliated Huai’an No.1 People's Hospital of Nanjing Medical University from January 2018 to September 2021 were selected and their targeted NGS data were retrospectively analyzed. Their diagnostic distribution and the gene mutation characteristics of patients with myeloid clonal hematopoiesis were observed. A ROC curve was plotted to analyze the diagnostic potential of number of gene mutations and variant allele fraction (VAF) for MDS and MDS/MPN patients. In addition, Kaplan-Meier survival analysis was used to evaluate the prognostic value of VAF and the number of mutations in newly diagnosed MDS patients.Results The 205 patients included 40 patients with idiopathic cytopenia of undetermined significance (ICUS), 47 patients with aplastic anemia (AA), 23 patients with clonal cytopenias of undetermined significance (CCUS), 79 patients with MDS, 13 patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and 3 patients with myeloproliferative neoplasms (MPN). For patients in the MDS/MPN, MDS and CCUS groups who were characterized by myeloid clonal hematopoiesis, their mean VAF value was 45.12% (7.90%-93.60%), 44.79% (8.70%-99.70%) and 34.83% (4.40%-94.60%), respectively (P=0.177 8), while their mean number of mutations was 2.462 (0-7), 1.886 (0-7), and 1.826 (1-4), respectively (P=0.459 3). Furthermore, VAF had a sensitivity of 78.9% and a specificity of 80.0%, with a cut-off value of 6.60%, when predicting the diagnosis of MDS and MDS/MPN. The number of gene mutations had a sensitivity of 78.9% and a specificity of 78.2%, with a cut-off value of 1, when predicting the diagnosis of MDS and MDS/MPN. However, the combination of the two indicators did not improve the diagnostic efficiency of MDS and MDS/MPN. Moreover, patients with VAF≥57.93% (n=13) showed poorer prognosis than those with VAF <57.93% (n=66), with shorter median overall survival (OS) (9.0 months vs not reached, P=0.000 5) and shorter median progression-free survival (PFS) (11.0 months vs not reached, P=0.007 9). In contrast, patients with ≥2 gene mutations (n=42) presented poorer prognosis than those with ＜2 gene mutations (n=37), with remarkable shorter median OS (33.0 months vs not reached, P=0.026 5), without statistical difference in median PFS (P=0.606 7). Conclusions The targeted NGS in this study is simple and practical. The number of gene mutations and VAF can be applied to predict the diagnosis and evalute the prognosis of MDS, with important clinical significance.