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

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 -