Fig. 3: Correlation of ALL drug sensitivities with MRD during induction therapy.
a,b, Forest plots depict drug LC50 correlation with day 15 MRD (B cell ALL, n = 671 patients; T cell ALL, n = 105 patients, representing biologically independent samples) (a) and day 42 MRD (B cell ALL, n = 669; T cell ALL, n = 105, representing biologically independent samples) (b). Left, Correlations with B cell ALL. Right, Correlations with T cell ALL. The coefficient of linear regression between each drug and MRD at each time point is shown as solid dots, with the 95% CIs indicated by the horizontal bars. Each unit change in coefficient represents a unit change of MRD (log10-transformed), that is, a coefficient of 1.0 represents a tenfold increase in MRD. Significant positive correlations are shown in red, negative correlations are shown in blue and those not reaching statistical significance are shown in black. c, Association of longitudinal MRD with B cell ALL sensitivity to prednisolone and L-asparaginase. LC50 of prednisolone (left, shades of pink/red) and L-asparaginase (right, shades of blue/teal) are plotted for 8 groups with different combinations of day 15 and day 42 MRD. The median LC50 of each group is shown as a bold horizontal black line for each violin plot, with the number of patients (biologically independent samples) in each category shown in parenthesis. In this study, the LC50 of both drugs increase progressively across MRD groups with rising MRD levels (P = 5.8 × 10−10 for prednisolone and P = 9.2 × 10−13 for L-asparaginase, determined by two-sided Kruskal–Wallis test). Additionally, the pattern of influence appears to differ between both drugs. Prednisolone LC50 was strikingly higher in MRD groups comprising high levels of MRD positivity but was relatively equal for MRD groups with low or no MRD. By contrast, L-asparaginase LC50 was strikingly lower only at complete day 15 and day 42 MRD negativity but was relatively equal for MRD groups with any degree of MRD positivity.
