医学
内科学
净现值1
髓系白血病
胃肠病学
移植
IDH1
肿瘤科
突变
生物
遗传学
基因
核型
染色体
作者
Talha Badar,Ahmad Nanaa,Ehab Atallah,Rory M. Shallis,Emily C. Craver,Zhuo Li,Aaron D. Goldberg,Antoine N. Saliba,Anand Patel,Jan Philipp Bewersdorf,Adam DuVall,Madelyn Burkart,Danielle Bradshaw,Yasmin Abaza,Maximilian Stahl,Neil Palmisiano,Guru Subramanian Guru Murthy,Amer M. Zeidan,Vamsi Kota,Mrinal M. Patnaik,Mark R. Litzow
出处
期刊:Haematologica
[Ferrata Storti Foundation]
日期:2024-05-30
被引量:1
标识
DOI:10.3324/haematol.2024.285000
摘要
While there is clear evidence to suggest poorer outcome associated with multi-hit (MH) TP53 mutation compared to single-hit (SH) in lower-risk myelodysplastic syndrome (MDS), data are conflicting in both higher-risk MDS and acute myeloid leukemia (AML). We conducted an indepth analysis utilizing data from 10 US academic institutions to study differences in molecular characteristics and outcomes of SH (n= 139) versus MH (n= 243) TP53MTAML. Complex cytogenetics (CG) were more common in MH compared to 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 significantly clustered with SH TP53MT AML. Survival after excluding patients who received best supportive care alone was dismal but not significantly different between SH and MH (event free survival [EFS]: 3.0 vs 2.20 months, p= 0.22/ overall survival [OS]: 8.50 vs 7.53 months, respectively, p= 0.13). In multivariable analysis, IDH1 mutation and allogeneic hematopoietic stem cell transplantation (allo-HCT) as a time-dependent covariate were associated with superior EFS (HR; 0.44, 95% CI: 0.19-1.01, p= 0.05/ HR; 0.34, 95% CI: 0.18-0.62, p<0.001) and OS (HR; 0.24, 95% CI: 0.08-0.71, p= 0.01/ HR; 0.28, 95% CI: 0.16-0.47, p<0.001). While complex CG (HR; 1.56, 95% CI: 1.01-2.40, p= 0.04) retained unfavorable significance for OS. Our analysis suggests that unlike in MDS, multihit TP53MT is less relevant in independently predicting outcomes in patients with AML.
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