Prognostic Value of Next-Generation Sequencing Data in Patients with Myelodysplastic Syndrome

AUTOIMMUNE THROMBOCYTOPENIA

NYu Tsvetkov1, EV Morozova1, IM Barkhatov1, IS Moiseev1, MV Barabanshchikova1, AV Tishkov2, DS Bug2, NV Petukhova2, EA Izmailova1, SN Bondarenko1, BV Afanasyev1

1 RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

2 Research Center for Bioinformatics, Academic Institute of Biomedicine, IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Nikolai Yur’evich Tsvetkov, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(911)233-48-77, +7(812)338-62-27; e-mail: nikolai.tcvetkov@yandex.ru

For citation: Tsvetkov NYu, Morozova EV, Barkhatov IM, et al. Prognostic Value of Next-Generation Sequencing Data in Patients with Myelodysplastic Syndrome. Clinical oncohematology. 2020;13(2):170–5 (In Russ).

DOI: 10.21320/2500-2139-2020-13-2-170-175

ABSTRACT

Aim. To assess the prognostic value of the mutation of DNA methylation genes, SF3B1, and TP53 in patients with myelodysplastic syndrome (MDS).

Materials & Methods. Out of 35 MDS patients included into the trial 2 had multilineage dysplasia, 13 with excess blasts-I, 19 with excess blasts-II, and 1 had 5q-syndrome (criteria WHO 2016). In 30 patients primary MDS was identified, in 5 patients it was detected after prior chemo- or radiotherapy. 25 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). According to IPSS-R there were 1 low-risk, 5 intermediate risk, 17 high-risk, and 12 very high-risk patients. Hypomethylating agents were administered to 28 patients. Median age of patients was 49 years (range 18–80 years). Next-generation sequencing was applied for identifying somatic mutations in DNA methylation genes (TET2, IDH1/2, ASXL1, and DNMT3A) as well as in SF3B1, TP53, IDH, and RUNX1. Time to progression (TTP) was defined as the time from the initial diagnosis to the date of acute leukemia diagnosis. Allo-HSCT- or antitumor therapy-associated death was considered as competing risk.

Results. Methylation gene analysis showed no mutation in 37 % of patients, in 40 % mutation was detected only in one of the genes, in 23 % mutation was identified in ≥ 2 genes. SF3B1 mutations were reported in 23 % and TP53 in 11 % of patients. Median follow-up was 25 months (range 5–116 months). Univariate analysis showed no considerable differences in overall survival depending on mutation status. Median TTP in the group with allo-HSCT was not achieved, in the group without allo-HSCT it was 6 months (p = 0.0001). In patients with no SF3B1 mutation median TTP was 35 months, in patients with this mutation it was not achieved (p = 0.043). With ≥ 2 mutations in methylation genes median TTP was 12 months, in other cases it was not achieved (p = 0.024). In cases of TP53 mutation median TTP was 6 months, in cases without this mutation it was 43 months (p = 0.023). Multivariate analysis confirmed unfavorable prognostic value of TP53 mutation or ≥ 2 mutations in methylation genes in terms of TTP regardless of the drug treatment or allo-HSCT performed (hazard ratio 7.1; 95% confidence interval 2.6–19.6; p = 0.0001).

Conclusion. The analysis of molecular markers yields additional data concerning the MDS prognosis. Further research is required to determine the prognostic value of molecular markers in clinical practice which will enable to individualize approaches to MDS treatment.

Keywords: myelodysplastic syndrome, molecular markers, mutations, next-generation sequencing, prognosis.

Received: December 27, 2019

Accepted: March 25, 2020

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