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Prognostic impact of circulating tumor DNA status post-allogeneic hematopoietic stem cell transplantation in AML and MDS.

著者 Nakamura S , Yokoyama K , Shimizu E , Yusa N , Kondoh K , Ogawa M , Takei T , Kobayashi A , Ito M , Isobe M , Konuma T , Kato S , Kasajima R , Wada Y , Nagamura-Inoue T , Yamaguchi R , Takahashi S , Imoto S , Miyano S , Tojo A
Blood.2019 Apr 01 ; ():.
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This study was performed to assess the utility of tumor-derived fragmentary DNA, or circulating tumor DNA (ctDNA), for identifying high-risk patients for relapse of acute myeloid leukemia and myelodysplastic syndrome (AML/MDS) after undergoing myeloablative allogeneic stem cell transplantation (alloSCT). We retrospectively collected tumor and available matched serum samples at diagnosis and 1 and 3 months post-alloSCT from 53 patients with AML/MDS. After identifying driver mutations in 51 patients using next-generation sequencing, we designed at least one personalized digital-PCR assay per case. Diagnostic ctDNA and matched tumor DNA exhibited excellent correlations with variant allele frequencies. Sixteen patients relapsed after a median of 7 months post-alloSCT. Both mutation-persistence (MP) in bone marrow at 1 and 3 months post-alloSCT and corresponding ctDNA-persistence (CP) in the matched serum (MP1 and MP3; CP1 and CP3, respectively) were comparably associated with higher 3-year cumulative incidence of relapse rates [MP1 vs. non-MP1: 72.9% vs. 13.8% (P = 0.0012); CP1 vs. non-CP1: 65.6% vs. 9.0% (P = 0.0002); MP3 vs. non-MP3; 80% vs. 11.6% (P = 0.0002); CP3 vs. non-CP3: 71.4% vs. 8.4% (P < 0.0001)]. We subsequently evaluated whether subset analysis of patients with three genes associated with clonal hematopoiesis, , , and (DTA), could also be helpful in relapse prediction. As a result, CP based on DTA gene mutations also had the prognostic effect on CIR. These results, for the first time, support the utility of ctDNA as a non-invasive prognostic biomarker in patients with AML/MDS, undergoing alloSCT.
PMID: 30936070 [PubMed - as supplied by publisher]
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