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Postallogeneic monitoring with molecular markers detected by pretransplant next-generation or Sanger sequencing predicts clinical relapse in patients with myelodysplastic/myeloproliferative neoplasms.
- Source :
- European Journal of Haematology; Mar2014, Vol. 92 Issue 3, p189-194, 6p
- Publication Year :
- 2014
-
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 5 yr was 46% (95% CI 28-64%) and was not influenced by any mutation. After a median of 6 months 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09024441
- Volume :
- 92
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- European Journal of Haematology
- Publication Type :
- Academic Journal
- Accession number :
- 94514579
- Full Text :
- https://doi.org/10.1111/ejh.12223