Prognostic impact of 'multi-hit' versus 'single-hit' TP53 alteration in patients with acute myeloid leukemia: Results from the Consortium on Myeloid Malignancies and Neoplastic Diseases Journal Article

   

Authors:	Badar, T.; Nanaa, A.; Atallah, E.; Shallis, R. M.; Craver, E. C.; Li, Z.; Goldberg, A. D.; Saliba, A. N.; Patel, A.; Bewersdorf, J. P.; Duvall, A.; Burkart, M.; Bradshaw, D.; Abaza, Y.; Stahl, M.; Palmisiano, N.; Murthy, G. S. G.; Zeidan, A. M.; Kota, V.; Patnaik, M. M.; Litzow, M. R.
Article Title:	Prognostic impact of 'multi-hit' versus 'single-hit' TP53 alteration in patients with acute myeloid leukemia: Results from the Consortium on Myeloid Malignancies and Neoplastic Diseases
Abstract:	While there is clear evidence to suggest poorer outcome associated with multi-hit (MH) TP53 mutation ( TP53( MT) ) compared to a single-hit (SH) mutation in lower-risk myelodysplastic syndrome (MDS), data are conflicting in both higher-risk MDS and acute myeloid leukemia (AML). We conducted an in-depth analysis utilizing data from ten US academic institutions to study differences in molecular characteristics and outcomes of SH (N=139) versus MH (N=243) TP53(MT) AML. Complex cytogenetics were more common in MH than in SH TP53MT AML (P<0.001); whereas ASXL1 (P<0.001), RAS (P<0.001), splicing factor (P=0.003), IDH1/2 (P=0.001), FLT3 ITD (P<0.001) and NPM1 (P=0.005) mutations clustered significantly with SH TP53(MT)AML. Survival after excluding patients who received best supportive care alone was dismal but not significantly different between patients with SH or MH disease (event-free survival: 3.0 vs. 2.20 months, respectively, P =0.22; overall survival: 8.50 vs. 7.53 months, respectively, P =0.13). In multivariable analysis, IDH1 mutation and allogeneic hematopoietic stem cell transplantation as a time-dependent covariate were associated with superior event-free survival (hazard ratio [HR]=0.44, 95% confidence interval [95% CI]: 0.19-1.01, P =0.05 and HR=0.34, 95% CI: 0.18-0.62, P <0.001) and overall survival (HR=0.24, 95% CI: 0.08-0.71, P =0.01 and HR=0.28, 95% CI: 0.16-0.47, P <0.001). Complex cytogenetics (HR=1.56, 95% CI: 1.01-2.40, P =0.04) retained an unfavorable significance for overall survival. Our analysis suggests that MH TP53(MT) is less relevant in independently predicting outcomes in patients with AML than in those with MDS.
Keywords:	classification; therapy; tp53 mutation
Journal Title:	Haematologica
Volume:	109
Issue:	11
ISSN:	0390-6078
Publisher:	Ferrata Storti Foundation
Date Published:	2024-11-01
Start Page:	3533
End Page:	3542
Language:	English
ACCESSION:	WOS:001371211100013
DOI:	10.3324/haematol.2024.285000
PROVIDER:	wos
PMCID:	PMC11532685
PUBMED:	38813716
Notes:	Source: Wos

https://synapse.mskcc.org/synapse/works/has_related_data_chk/221474