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. 2022 Aug 1;128(15):2922-2931.
doi: 10.1002/cncr.34268. Epub 2022 May 25.

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

Justin Loke  1   2 , Myriam Labopin  3   4   5 , Charles Craddock  1   2 , Jan J Cornelissen  6 , Hélène Labussière-Wallet  7 , Eva Maria Wagner-Drouet  8 , Gwendolyn Van Gorkom  9 , Nicolaas P M Schaap  10 , Nicolaus M Kröger  11 , Joan Hendrik Veelken  12 , Montserrat Rovira  13 , Anne Lise Menard  14 , Gesine Bug  15 , Ali Bazarbachi  16   17 , Sebastian Giebel  18 , Eolia Brissot  4   5 , Arnon Nagler  19 , Jordi Esteve  13 , Mohamad Mohty  4   5
Affiliations

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

Justin Loke et al. Cancer. .

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: TP53; acute myeloid; allogeneic stem cell transplant; cytogenetics; leukemia.

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Conflict of interest statement

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.

Figures

FIGURE 1
FIGURE 1
(A) RI, (B) NRM, (C) LFS, and (D) OS from time of transplant for patients with AML with or without mutations at TP53 post allogeneic stem cell transplantation. AML indicates acute myeloid leukemia; LFS, leukemia‐free survival; NRM, nonrelapse mortality; OS, overall survival; RI, relapse incidence.
FIGURE 2
FIGURE 2
(A) RI, (B) NRM, (C) LFS, and (D) OS for patients with TP53 mutant AML with or without abnormalities at chromosome 17p (−17 or del(17p)) or complex karyotype. AML indicates acute myeloid leukemia; LFS, leukemia‐free survival; NRM, nonrelapse mortality; OS, overall survival; RI, relapse incidence.
See this image and copyright information in PMC

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