title: 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 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.
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Fu
authors.forename: Thomas
authors.initials: T
authors.lastname: Schroeder
authors.forename: Tatjana
authors.initials: T
authors.lastname: Zabelina
authors.forename: Anita
authors.initials: A
authors.lastname: Badbaran
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bacher
authors.forename: Guido
authors.initials: G
authors.lastname: Kobbe
authors.forename: Francis
authors.initials: F
authors.lastname: Ayuk
authors.forename: Christine
authors.initials: C
authors.lastname: Wolschke
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Alexander
authors.initials: A
authors.lastname: Kohlmann
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D054437:Myelodysplastic-Myeloproliferative Diseases / Q000628:therapy*; D011237:Predictive Value of Tests; D012008:Recurrence; D033581:Stem Cell Transplantation; D013997:Time Factors; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: Sanger; allogeneic stem-cell transplantation; minimal residual disease; myelodysplastic/myeloproliferative neoplasms; next-generation sequencing; relapse prevention