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

Bone Marrow Transplantation volume 56, pages 334–346 (2021)Cite this article

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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.

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Fig. 1: Transplant outcomes of patients with nonremission AML at the time of allo-HSCT.
Fig. 2: Landscape of gene abnormalities in nonremission AML patients at the time of allo-HSCT.
Fig. 3: Karyotypic profiles and their prognostic impact.
Fig. 4: TP53 mutation profile and its prognostic impact.
Fig. 5: Prognostic impact of the combination of three factors.
Fig. 6: Risk stratification according to pretransplant factors.

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Acknowledgements

The present research work was supported by Clinical Research Fund of Tokyo Metropolitan Government.

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  1. These authors contributed equally: Yuho Najima, Daichi Sadato

Authors and Affiliations

  1. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

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

  2. Clinical Research Support Center, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Daichi Sadato, Yuka Harada & Chizuko Hirama

  3. Center for Medical Research Cooperation, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

    Daichi Sadato, Keisuke Oboki & Chizuko Hirama

  4. Division of Transfusion and Cell Therapy, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Kyoko Haraguchi & Yoshiki Okuyama

  5. Laboratory of Oncology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

    Hironori Harada

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Contributions

YN, YH, K. Oboki, HH, and K. Ohashi designed the study. DS and CH performed NGS analysis. YN, DS, YH, K. Oboki, and HH carried out research and analyzed data. YN, TT, ND, KH, and YO collected patients’ samples. YN, TT, ND, KY, MA, KI, AI, TK, KK, HS, HH, and K. Ohashi performed patient care. YN, YH, K. Oboki, TT, and K. Ohashi wrote the manuscript. All the authors reviewed and approved the final manuscript.

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Correspondence to Yuka Harada.

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Najima, Y., Sadato, D., Harada, Y. et al. Prognostic impact of TP53 mutation, monosomal karyotype, and prior myeloid disorder in nonremission acute myeloid leukemia at allo-HSCT. Bone Marrow Transplant 56, 334–346 (2021). https://doi.org/10.1038/s41409-020-01016-9

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