Prognostic impact of circulating tumor DNA status post-allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia and myelodysplastic syndromes

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  • YOKOYAMA Kazuaki
    Department of Hematology and Oncology, Research Hospital, The Institute of Medical Science, the University of Tokyo

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  • 急性骨髄性白血病や骨髄異形成症候群において同種移植後の循環腫瘍DNA残存は再発を予測するバイオマーカーである
  • キュウセイ コツズイセイ ハッケツビョウ ヤ コツズイイケイセイ ショウコウグン ニ オイテ ドウシュ イショク ゴ ノ ジュンカン シュヨウ DNA ザンソン ワ サイハツ オ ヨソク スル バイオマーカー デ アル

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Abstract

<p>Relapse is an issue of concern for patients with acute myeloid leukemia and myelodysplastic syndromes (AML/MDS) who underwent allogeneic hematopoietic stem cell transplantation (allo HSCT). The conventional minimal residual disease (MRD) test of the bone marrow has serious limitations regarding invasiveness and applicability. To address this problem, we investigated the utility of a novel MRD test using tumor-derived fragmentary DNA, or circulating tumor DNA (ctDNA) for the identification of patients with high risk of AML/MDS relapse after undergoing myeloablative allo HSCT. We retrospectively collected tumor specimens and available matched serum samples at diagnosis and at 1 and 3 months post-allo HSCT from 53 patients with AML/MDS. After identifying driver mutations in 51 patients using next-generation sequencing, we designed at least one personalized digital polymerase chain reaction 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 allo HSCT. Both the mutation persistence in the bone marrow at 1 and 3 months post allo HSCT and the corresponding ctDNA persistence in the matched serum were comparably associated with higher 3-year cumulative incidence of relapse rates. These results demonstrate, for the first time, the utility of ctDNA as a noninvasive prognostic biomarker in patients with AML/MDS who underwent allo HSCT.</p>

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  • Rinsho Ketsueki

    Rinsho Ketsueki 62 (5), 486-495, 2021

    The Japanese Society of Hematology

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