Postallogeneic monitoring with molecular markers detected by pretransplant next-generation or Sanger sequencing predicts clinical relapse in patients with myelodysplastic/myeloproliferative neoplasms
Standard
Postallogeneic monitoring with molecular markers detected by pretransplant next-generation or Sanger sequencing predicts clinical relapse in patients with myelodysplastic/myeloproliferative neoplasms. / Fu, Yuewen; Schroeder, Thomas; Zabelina, Tatiana; Badbaran, Anita; Bacher, Ulrike; Kobbe, Guido; Ayuketang, Francis Ayuk; Wolschke, Christine; Schnittger, Susanne; Kohlmann, Alexander; Haferlach, Torsten; Kröger, Nicolaus.
in: EUR J HAEMATOL, Jahrgang 92, Nr. 3, 01.03.2014, S. 189-94.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Postallogeneic monitoring with molecular markers detected by pretransplant next-generation or Sanger sequencing predicts clinical relapse in patients with myelodysplastic/myeloproliferative neoplasms
AU - Fu, Yuewen
AU - Schroeder, Thomas
AU - Zabelina, Tatiana
AU - Badbaran, Anita
AU - Bacher, Ulrike
AU - Kobbe, Guido
AU - Ayuketang, Francis Ayuk
AU - Wolschke, Christine
AU - Schnittger, Susanne
AU - Kohlmann, Alexander
AU - Haferlach, Torsten
AU - Kröger, Nicolaus
N1 - © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
PY - 2014/3/1
Y1 - 2014/3/1
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - DNA Mutational Analysis
KW - Disease-Free Survival
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Mutation
KW - Myelodysplastic-Myeloproliferative Diseases
KW - Predictive Value of Tests
KW - Recurrence
KW - Stem Cell Transplantation
KW - Time Factors
KW - Transplantation, Homologous
KW - Tumor Markers, Biological
KW - Young Adult
U2 - 10.1111/ejh.12223
DO - 10.1111/ejh.12223
M3 - SCORING: Journal article
C2 - 24164563
VL - 92
SP - 189
EP - 194
JO - EUR J HAEMATOL
JF - EUR J HAEMATOL
SN - 0902-4441
IS - 3
ER -