Postallogeneic monitoring with molecular markers detected by pretransplant next-generation or Sanger sequencing predicts clinical relapse in patients with myelodysplastic/myeloproliferative neoplasms.
Eur J Haematol
; 92(3): 189-94, 2014 Mar.
Article
em En
| MEDLINE
| ID: mdl-24164563
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante Homólogo
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Transplante de Células-Tronco
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Doenças Mieloproliferativas-Mielodisplásicas
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article