Additional cytogenetic features determine outcome in patients allografted for TP53 mutant acute myeloid leukemia

Justin Loke; Myriam Labopin; Charles Craddock; Jan J. Cornelissen; Hélène Labussière-Wallet; Eva Maria Wagner-Drouet; Gwendolyn Van Gorkom; Nicolaas P.M. Schaap; Nicolaus M. Kröger; Joan Hendrik Veelken; Montserrat Rovira; Anne Lise Menard; Gesine Bug; Ali Bazarbachi; Sebastian Giebel; Eolia Brissot; Arnon Nagler; Jordi Esteve; Mohamad Mohty

doi:10.1002/cncr.34268

Additional cytogenetic features determine outcome in patients allografted for TP53 mutant acute myeloid leukemia

Justin Loke, Myriam Labopin, Charles Craddock, Jan J. Cornelissen, Hélène Labussière-Wallet, Eva Maria Wagner-Drouet, Gwendolyn Van Gorkom, Nicolaas P.M. Schaap, Nicolaus M. Kröger, Joan Hendrik Veelken, Montserrat Rovira, Anne Lise Menard, Gesine Bug, Ali Bazarbachi, Sebastian Giebel, Eolia Brissot, Arnon Nagler, Jordi Esteve, Mohamad Mohty^*

^*Corresponding author for this work

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Abstract

BACKGROUND: The presence of TP53 mutations is associated with an unfavorable outcome in patients allografted for acute myeloid leukemia (AML), leading some to question the benefit of an allogeneic stem cell transplantation (allo-SCT) for this patient group, although this has not been studied in a large cohort. METHODS: A total of 780 patients with AML in first complete remission, with either intermediate- or adverse-risk cytogenetics, whose TP53 mutation status was reported, were included in this study from the European Society for Blood and Marrow Transplantation. RESULTS: Two-year overall survival (OS) was impaired in patients (n = 179) with evidence of a TP53 mutation at diagnosis (35.1%; 95% confidence interval [CI], 26.7–43.7) as compared to the cohort without (n = 601) (64%; 95% CI, 59.1–68.4; P =.001). In patients with mutant TP53 AML with no evidence of either chromosome 17p loss (17p–) and/or complex karyotype (CK) (n = 53, 29.6%), 2-year OS was 65.2% (95% CI, 48.4–77.6). This was not significantly different to patients without TP53 mutations. In patients with mutant TP53 AML with either 17p– and/or CK (n = 126, 70.4%), the OS was lower (24.6%; 95% CI, 16.2–34; P =.001). CONCLUSIONS: In summary, the adverse prognostic effect of TP53 mutations in AML following an allo-SCT is not evident in patients with neither co-occurring 17p– and/or CK, and these data inform decisions regarding allo-SCT in patients with TP53 mutant AML.

Original language	English
Pages (from-to)	2922-2931
Number of pages	10
Journal	Cancer
Volume	128
Issue number	15
Early online date	25 May 2022
DOIs	https://doi.org/10.1002/cncr.34268
Publication status	Published - 1 Aug 2022

Bibliographical note

Funding Information:
Gesine Bug reports a grant (paid to her institution) from Novartis; honoraria from Jazz Pharmaceuticals (paid to her institution), Celgene, and Gilead; support for attending meetings and/or travel from Jazz Pharmaceuticals, Gilead, and Neovii; and payment for participation on an advisory board from Novartis, Pfizer, Eurocept, Gilead, and Celgene. Charles Craddock reports grants from Celgene, Bloodwise, Cancer Research UK, and Cure Leukemia; and honoraria from Celgene, Daichi‐Sankyo, Novartis, and Pfizer. Justin Loke reports payment or honoraria from Pfizer, Janssen and Amgen; and travel support from Novartis and Daichi‐Sankyo. The other authors made no disclosures.

This work was supported by research support and clinical trials funding from Cancer Research UK, Cure Leukemia, and Bloodwise.

Publisher Copyright:
© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.

Keywords

acute myeloid
allogeneic stem cell transplant
cytogenetics
leukemia
TP53

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Loke, J., Labopin, M., Craddock, C., Cornelissen, J. J., Labussière-Wallet, H., Wagner-Drouet, E. M., Van Gorkom, G., Schaap, N. P. M., Kröger, N. M., Veelken, J. H., Rovira, M., Menard, A. L., Bug, G., Bazarbachi, A., Giebel, S., Brissot, E., Nagler, A., Esteve, J., & Mohty, M. (2022). Additional cytogenetic features determine outcome in patients allografted for TP53 mutant acute myeloid leukemia. Cancer, 128(15), 2922-2931. https://doi.org/10.1002/cncr.34268

@article{91aab5e74a994d61b703bdbb7fea1f6d,

title = "Additional cytogenetic features determine outcome in patients allografted for TP53 mutant acute myeloid leukemia",

abstract = "BACKGROUND: The presence of TP53 mutations is associated with an unfavorable outcome in patients allografted for acute myeloid leukemia (AML), leading some to question the benefit of an allogeneic stem cell transplantation (allo-SCT) for this patient group, although this has not been studied in a large cohort. METHODS: A total of 780 patients with AML in first complete remission, with either intermediate- or adverse-risk cytogenetics, whose TP53 mutation status was reported, were included in this study from the European Society for Blood and Marrow Transplantation. RESULTS: Two-year overall survival (OS) was impaired in patients (n = 179) with evidence of a TP53 mutation at diagnosis (35.1%; 95% confidence interval [CI], 26.7–43.7) as compared to the cohort without (n = 601) (64%; 95% CI, 59.1–68.4; P =.001). In patients with mutant TP53 AML with no evidence of either chromosome 17p loss (17p–) and/or complex karyotype (CK) (n = 53, 29.6%), 2-year OS was 65.2% (95% CI, 48.4–77.6). This was not significantly different to patients without TP53 mutations. In patients with mutant TP53 AML with either 17p– and/or CK (n = 126, 70.4%), the OS was lower (24.6%; 95% CI, 16.2–34; P =.001). CONCLUSIONS: In summary, the adverse prognostic effect of TP53 mutations in AML following an allo-SCT is not evident in patients with neither co-occurring 17p– and/or CK, and these data inform decisions regarding allo-SCT in patients with TP53 mutant AML.",

keywords = "acute myeloid, allogeneic stem cell transplant, cytogenetics, leukemia, TP53",

author = "Justin Loke and Myriam Labopin and Charles Craddock and Cornelissen, {Jan J.} and H{\'e}l{\`e}ne Labussi{\`e}re-Wallet and Wagner-Drouet, {Eva Maria} and {Van Gorkom}, Gwendolyn and Schaap, {Nicolaas P.M.} and Kr{\"o}ger, {Nicolaus M.} and Veelken, {Joan Hendrik} and Montserrat Rovira and Menard, {Anne Lise} and Gesine Bug and Ali Bazarbachi and Sebastian Giebel and Eolia Brissot and Arnon Nagler and Jordi Esteve and Mohamad Mohty",

note = "Funding Information: Gesine Bug reports a grant (paid to her institution) from Novartis; honoraria from Jazz Pharmaceuticals (paid to her institution), Celgene, and Gilead; support for attending meetings and/or travel from Jazz Pharmaceuticals, Gilead, and Neovii; and payment for participation on an advisory board from Novartis, Pfizer, Eurocept, Gilead, and Celgene. Charles Craddock reports grants from Celgene, Bloodwise, Cancer Research UK, and Cure Leukemia; and honoraria from Celgene, Daichi‐Sankyo, Novartis, and Pfizer. Justin Loke reports payment or honoraria from Pfizer, Janssen and Amgen; and travel support from Novartis and Daichi‐Sankyo. The other authors made no disclosures. This work was supported by research support and clinical trials funding from Cancer Research UK, Cure Leukemia, and Bloodwise. Publisher Copyright: {\textcopyright} 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.",

year = "2022",

month = aug,

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doi = "10.1002/cncr.34268",

language = "English",

volume = "128",

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Loke, J, Labopin, M, Craddock, C, Cornelissen, JJ, Labussière-Wallet, H, Wagner-Drouet, EM, Van Gorkom, G, Schaap, NPM, Kröger, NM, Veelken, JH, Rovira, M, Menard, AL, Bug, G, Bazarbachi, A, Giebel, S, Brissot, E, Nagler, A, Esteve, J & Mohty, M 2022, 'Additional cytogenetic features determine outcome in patients allografted for TP53 mutant acute myeloid leukemia', Cancer, vol. 128, no. 15, pp. 2922-2931. https://doi.org/10.1002/cncr.34268

TY - JOUR

T1 - Additional cytogenetic features determine outcome in patients allografted for TP53 mutant acute myeloid leukemia

AU - Loke, Justin

AU - Labopin, Myriam

AU - Craddock, Charles

AU - Cornelissen, Jan J.

AU - Labussière-Wallet, Hélène

AU - Wagner-Drouet, Eva Maria

AU - Van Gorkom, Gwendolyn

AU - Schaap, Nicolaas P.M.

AU - Kröger, Nicolaus M.

AU - Veelken, Joan Hendrik

AU - Rovira, Montserrat

AU - Menard, Anne Lise

AU - Bug, Gesine

AU - Bazarbachi, Ali

AU - Giebel, Sebastian

AU - Brissot, Eolia

AU - Nagler, Arnon

AU - Esteve, Jordi

AU - Mohty, Mohamad

N1 - Funding Information: Gesine Bug reports a grant (paid to her institution) from Novartis; honoraria from Jazz Pharmaceuticals (paid to her institution), Celgene, and Gilead; support for attending meetings and/or travel from Jazz Pharmaceuticals, Gilead, and Neovii; and payment for participation on an advisory board from Novartis, Pfizer, Eurocept, Gilead, and Celgene. Charles Craddock reports grants from Celgene, Bloodwise, Cancer Research UK, and Cure Leukemia; and honoraria from Celgene, Daichi‐Sankyo, Novartis, and Pfizer. Justin Loke reports payment or honoraria from Pfizer, Janssen and Amgen; and travel support from Novartis and Daichi‐Sankyo. The other authors made no disclosures. This work was supported by research support and clinical trials funding from Cancer Research UK, Cure Leukemia, and Bloodwise. Publisher Copyright: © 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.

PY - 2022/8/1

Y1 - 2022/8/1

N2 - BACKGROUND: The presence of TP53 mutations is associated with an unfavorable outcome in patients allografted for acute myeloid leukemia (AML), leading some to question the benefit of an allogeneic stem cell transplantation (allo-SCT) for this patient group, although this has not been studied in a large cohort. METHODS: A total of 780 patients with AML in first complete remission, with either intermediate- or adverse-risk cytogenetics, whose TP53 mutation status was reported, were included in this study from the European Society for Blood and Marrow Transplantation. RESULTS: Two-year overall survival (OS) was impaired in patients (n = 179) with evidence of a TP53 mutation at diagnosis (35.1%; 95% confidence interval [CI], 26.7–43.7) as compared to the cohort without (n = 601) (64%; 95% CI, 59.1–68.4; P =.001). In patients with mutant TP53 AML with no evidence of either chromosome 17p loss (17p–) and/or complex karyotype (CK) (n = 53, 29.6%), 2-year OS was 65.2% (95% CI, 48.4–77.6). This was not significantly different to patients without TP53 mutations. In patients with mutant TP53 AML with either 17p– and/or CK (n = 126, 70.4%), the OS was lower (24.6%; 95% CI, 16.2–34; P =.001). CONCLUSIONS: In summary, the adverse prognostic effect of TP53 mutations in AML following an allo-SCT is not evident in patients with neither co-occurring 17p– and/or CK, and these data inform decisions regarding allo-SCT in patients with TP53 mutant AML.

AB - BACKGROUND: The presence of TP53 mutations is associated with an unfavorable outcome in patients allografted for acute myeloid leukemia (AML), leading some to question the benefit of an allogeneic stem cell transplantation (allo-SCT) for this patient group, although this has not been studied in a large cohort. METHODS: A total of 780 patients with AML in first complete remission, with either intermediate- or adverse-risk cytogenetics, whose TP53 mutation status was reported, were included in this study from the European Society for Blood and Marrow Transplantation. RESULTS: Two-year overall survival (OS) was impaired in patients (n = 179) with evidence of a TP53 mutation at diagnosis (35.1%; 95% confidence interval [CI], 26.7–43.7) as compared to the cohort without (n = 601) (64%; 95% CI, 59.1–68.4; P =.001). In patients with mutant TP53 AML with no evidence of either chromosome 17p loss (17p–) and/or complex karyotype (CK) (n = 53, 29.6%), 2-year OS was 65.2% (95% CI, 48.4–77.6). This was not significantly different to patients without TP53 mutations. In patients with mutant TP53 AML with either 17p– and/or CK (n = 126, 70.4%), the OS was lower (24.6%; 95% CI, 16.2–34; P =.001). CONCLUSIONS: In summary, the adverse prognostic effect of TP53 mutations in AML following an allo-SCT is not evident in patients with neither co-occurring 17p– and/or CK, and these data inform decisions regarding allo-SCT in patients with TP53 mutant AML.

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KW - allogeneic stem cell transplant

KW - cytogenetics

KW - leukemia

KW - TP53

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DO - 10.1002/cncr.34268

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SN - 0008-543X

VL - 128

SP - 2922

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JO - Cancer

JF - Cancer

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ER -

Additional cytogenetic features determine outcome in patients allografted for TP53 mutant acute myeloid leukemia

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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