The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Prognostic and therapeutic impacts of mutant TP53 variant allelic frequency in newly diagnosed acute myeloid leukemia
Open accessAbstract
TP53 mutations are associated with poor outcomes in acute myeloid leukemia (AML). The prognostic impact of mutant TP53 (TP53mut) variant allelic frequency (VAF) is not well established, nor is how this information might guide optimal frontline therapy. We retrospectively analyzed 202 patients with newly diagnosed TP53-mutated AML who underwent first-line therapy with either a cytarabine- or hypomethylating agent (HMA)–based regimen. By multivariate analysis, TP53mut VAF >40% was independently associated with a significantly higher cumulative incidence of relapse (P = .003) and worse relapse-free survival (P = .001) and overall survival (OS; P = .003). The impact of TP53mut VAF on clinical outcomes was driven by patients treated with a cytarabine-based regimen (median OS, 4.7 vs 7.3 months for VAF >40% vs ≤40%; P = .006), whereas VAF did not significantly affect OS in patients treated with HMA. The addition of venetoclax to HMA did not significantly affect OS compared with HMA without venetoclax, both in the entire TP53-mutated population and in patients stratified by TP53mut VAF. Among patients with TP53mut VAF ≤40%, OS was superior in those treated with higher-dose cytarabine, whereas OS was similarly poor for patients with TP53mut VAF >40% regardless of therapy. The best long-term outcomes were observed in those with 1 TP53 mutation with VAF ≤40% who received a frontline cytarabine-based regimen (2-year OS, 38% vs 6% for all others; P < .001). In summary, TP53mut VAF provides important prognostic information that may be considered when selecting frontline therapy for patients with newly diagnosed TP53-mutated AML.
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Cites
Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia
Wong, T. N., Ramsingh, G., Young, A. L., Miller, C. A., Touma, W., Welch, J. S., Lamprecht, T. L., Shen, D., Hundal, J., Fulton, R. S., et al. (2015) · Nature · doi:10.1038/nature13968 · Cited by 892
Lehmann, S., Bykov, V. J. N., Ali, D., Andrén, O., Cherif, H., Tidefelt, U., Uggla, B., Yachnin, J., Juliusson, G., Moshfegh, A., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.40.7783 · Cited by 406
Montalban-Bravo, G., Kanagal-Shamanna, R., Benton, C. B., Class, C. A., Chien, K. S., Sasaki, K., Naqvi, K., Alvarado, Y., Kadia, T. M., Ravandi, F., et al. (2020) · Blood Advances · doi:10.1182/bloodadvances.2019001101 · Cited by 133
Self-citationTreated secondary acute myeloid leukemia: a distinct high-risk subset of AML with adverse prognosis
Boddu, P., Kantarjian, H. M., Garcia-Manero, G., Ravandi, F., Verstovsek, S., Jabbour, E., Borthakur, G., Konopleva, M., Bhalla, K. N., Daver, N., et al. (2017) · Blood Advances · doi:10.1182/bloodadvances.2017008227 · Cited by 112
Self-citationSasaki, K., Kanagal‐Shamanna, R., Montalban‐Bravo, G., Assi, R., Jabbour, E., Ravandi, F., Kadia, T., Pierce, S., Takahashi, K., Nogueras Gonzalez, G., et al. (2020) · Cancer · doi:10.1002/cncr.32566 · Cited by 101 · cited 1×
“In contrast, previous retrospective studies in AML have yielded conflicting data as to whether higher TP53 VAF is predictive for clinical outcomes.(6,13,14) Notably, these reports were not designed to assess whether the impact of TP53 VAF on outcomes might be treatment dependent.”
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Cited by
Grob, T., Al Hinai, A. S. A., Sanders, M. A., Kavelaars, F. G., Rijken, M., Gradowska, P. L., Biemond, B. J., Breems, D. A., Maertens, J., van Marwijk Kooy, M., et al. (2022) · Blood · doi:10.1182/blood.2021014472 · Cited by 305
Outcomes of TP53‐mutant acute myeloid leukemia with decitabine and venetoclax
Kim, K., Maiti, A., Loghavi, S., Pourebrahim, R., Kadia, T. M., Rausch, C. R., Furudate, K., Daver, N. G., Alvarado, Y., Ohanian, M., et al. (2021) · Cancer · doi:10.1002/cncr.33689 · Cited by 161
Self-citationPollyea, D. A., Pratz, K. W., Wei, A. H., Pullarkat, V., Jonas, B. A., Recher, C., Babu, S., Schuh, A. C., Dail, M., Sun, Y., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-1183 · Cited by 159
Self-citationMishra, A., Tamari, R., DeZern, A. E., Byrne, M. T., Gooptu, M., Chen, Y.-B., Deeg, H. J., Sallman, D., Gallacher, P., Wennborg, A., et al. (2022) · Journal of Clinical Oncology · doi:10.1200/jco.22.00181 · Cited by 146
Tashakori, M., Kadia, T., Loghavi, S., Daver, N., Kanagal-Shamanna, R., Pierce, S., Sui, D., Wei, P., Khodakarami, F., Tang, Z., et al. (2022) · Blood · doi:10.1182/blood.2021013983 · Cited by 111
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Metadata
- Authors
- Short, N. J., Montalban-Bravo, G., Hwang, H., Ning, J., Franquiz, M. J., Kanagal-Shamanna, R., Patel, K. P., DiNardo, C. D., Ravandi, F., Garcia-Manero, G., Takahashi, K., Konopleva, M., Daver, N., Issa, G. C., Andreeff, M., Kantarjian, H., & Kadia, T. M.
- Venue
- Blood Advances
- Publisher
- American Society of Hematology
- Published
- 2020-11-19
- Volume
- 4
- Issue
- 22
- Pages
- 5681-5689
- ISSN
- 2473-9529 (ISSN-L)
- 2473-9537
- OpenAlex
- W3101740872
- Cited by
- 179
- References
- 5
- FWCI
- 14.31
- Type
- journal article
- Language
- en
- Open access
- gold
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- Short, N. J., Montalban-Bravo, G., Hwang, H., Ning, J., Franquiz, M. J., Kanagal-Shamanna, R., Patel, K. P., DiNardo, C. D., Ravandi, F., Garcia-Manero, G., Takahashi, K., Konopleva, M., Daver, N., Issa, G. C., Andreeff, M., Kantarjian, H., & Kadia, T. M. (2020). Prognostic and therapeutic impacts of mutant TP53 variant allelic frequency in newly diagnosed acute myeloid leukemia. Blood Advances. https://doi.org/10.1182/bloodadvances.2020003120
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