Factors influencing clonal expansion of TP53-mutated subclones. (A) Forrest plot depicting the factors influencing the risk of clonal expansion above the median fold change. *Continual parameter. †As assessed by Kato et al,⁴⁷ data downloaded from Seshat.²⁸ ‡Average of promoters: WAF1, MDM2, BAX, 14_3_3_s, AIP, GADD45, NOXA, and p53R2, as assessed by Kato et al,⁷ data downloaded from Seshat.²⁸ Null mutations: nonsense, frameshift, and splice site. In frame mutations excluded from analysis. DNA binding motif as classified by Cho et al.⁴⁸ #Frequency of mutations categorized according to Seshat²⁸: frequent (very frequent+frequent) vs not frequent+rare+unique+never identified. CR, complete remission. §Fludarabine cumulative dose calculated in FCR-treated patients only. (B) Risk of clonal expansion for patients treated with FCR (orange) and other regimens (black). (C) Risk of clonal expansion for patients reaching (dark blue) and not reaching (light blue) CR. (D) Fold change in mutation proportion in first relapse compared with pretherapy sample in order according fold change. Logarithmic scale x-axis label shows pretherapy VAF. Patients treated with FCR are depicted in orange. Patients treated with other regimens are in black. Patients treated with BR are depicted with a gray arrow. (E) Mutation burden in the first and second relapse in patients with low-burden TP53 mutations treated with second-line FCR. Dashed line, 10% VAF threshold. For cumulative VAF see supplemental Figure 10C. (F) Mutation burden in untreated patients at diagnosis and before therapy in patients with low-burden TP53 mutations. Dashed line, 10% VAF threshold.