Postallogeneic monitoring with molecular markers detected by pretransplant next‐generation or Sanger sequencing predicts clinical relapse in patients with myelodysplastic/myeloproliferative neoplasms

Abstract

Relapse is the major cause of treatment failure after allogeneic stem-cell transplantation (AHSCT) for patients with myelodysplastic syndrome/myeloproliferative syndrome neoplasms (MDS/MPN). We evaluated the impact of molecular mutations on outcome and the value of molecular monitoring post-transplantation. We screened 45 patients with chronic myelomonocytic leukemia (n=39 patients, including seven with transformed-acute myeloid leukemia), MDS/MPN unclassifiable (n=5), and atypical BCR-ABL1-negative CML (n=1) for mutations in ASXL1, CBL, NRAS, and TET2 genes by molecular genetics including a sensitive next-generation sequencing (NGS) technique. In 36 patients, sufficient DNA was available for molecular analyses. In particular, TET2 and CBL mutations were screened applying amplicon deep sequencing. In 89% of cases, at least one mutation could be detected: ASXL1: n=18 (50%); CBL: n=7 (19%); TET2: n=15 (42%); and NRAS: n=11 (32%). Survival after AHSCT at 5yr was 46% (95% CI 28-64%) and was not influenced by any mutation. After a median of 6months after AHSCT in 33% of the patients, one of the molecular markers was still detectable, resulting in a higher incidence of relapse than in patients with undetectable mutations (50% vs. 15%, P=0.04). In conclusion, pretransplant molecular mutation analysis can help to detect biomarkers in patients with MPN/MDS, which may be subsequently used as minimal residual disease markers after AHSCT.