Prognostic impact of TP53 mutation, monosomal karyotype, and prior myeloid disorder in nonremission acute myeloid leukemia at allo-HSCT View Full Text


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Article Info

DATE

2020-08-05

AUTHORS

Yuho Najima, Daichi Sadato, Yuka Harada, Keisuke Oboki, Chizuko Hirama, Takashi Toya, Noriko Doki, Kyoko Haraguchi, Kota Yoshifuji, Megumi Akiyama, Kyoko Inamoto, Aiko Igarashi, Takeshi Kobayashi, Kazuhiko Kakihana, Yoshiki Okuyama, Hisashi Sakamaki, Hironori Harada, Kazuteru Ohashi

ABSTRACT

Outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in nonremission acute myeloid leukemia (AML) are dismal [2-year overall survival (OS): 20–30%]. Though several risk classifications have been used, some factors are unavailable until the start of conditioning or transplantation. We analyzed prognostic gene mutations by targeted next-generation sequencing to identify predisposing factors for predicting OS at 1 month before transplantation. We enrolled 120 patients with nonremission AML who underwent first allo-HSCT between 2005 and 2018. Mutations were found in 98 patients; frequently mutated genes were FLT3-ITD, TP53, RUNX1, and WT1. TP53 mutation was detected in 21 patients and was the only predictor of poor OS. Multivariate analysis using Cox regression hazard model revealed primary AML, monosomal karyotype (MK), and TP53 mutation as independent factors for predicting poor OS. Based on these, patients were stratified into three groups. The low-risk group included patients with prior myeloid disorder without MK (n = 26). Among the rest, patients with TP53 mutation were assigned to the high-risk group (n = 19) and the rest into the intermediate-risk group (n = 75). Two-year OS in low-, intermediate-, and high-risk groups differed significantly (50.0%, 24.9%, and 0%, respectively). This suggests that the indication of allo-HSCT should be carefully judged for high-risk patients. More... »

PAGES

334-346

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41409-020-01016-9

    DOI

    http://dx.doi.org/10.1038/s41409-020-01016-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1129875900

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/32760007


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    329 Laboratory of Oncology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
    330 rdf:type schema:Organization
    331 grid-institutes:grid.415479.a schema:alternateName Clinical Research Support Center, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
    332 Division of Transfusion and Cell Therapy, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
    333 Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
    334 schema:name Clinical Research Support Center, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
    335 Division of Transfusion and Cell Therapy, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
    336 Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
    337 rdf:type schema:Organization
     




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