Table 4.
Multivariable Models for Clinical Outcome in the Training Set of Patients With Cytogenetically Normal Acute Myeloid Leukemia
| Variables in Final Model* | OR/HR | 95% CI | P |
|---|---|---|---|
| CR | |||
| Weighted summary score,† high v low | 0.17 | 0.07 to 0.41 | .01 |
| NPM1, mutated v wild-type | 2.37 | 1.00 to 5.59 | .05 |
| DFS | |||
| Weighted summary score,† high v low | 3.59 | 1.83 to 7.03 | < .001 |
| ERG expression, high v low | 1.93 | 1.04 to 3.55 | .04 |
| OS | |||
| Weighted summary score,† high v low | 3.41 | 2.13 to 5.47 | < .001 |
| DNMT3A, R882 v wild-type or non-R882 | 2.35 | 1.38 to 4.00 | .002 |
| BAALC expression, high v low | 1.73 | 1.10 to 2.71 | .02 |
| Platelets, continuous, 50-unit increase | 1.16 | 1.02 to 1.33 | .02 |
Abbreviations: CR, complete remission; DFS, disease-free survival; HR, hazard ratio; OR, odds ratio; OS, overall survival.
Variables that were significant at P < .20 in univariable models were considered for multivariable model inclusion and were as follows: for CR, weighted summary score (high v low), NPM1 (mutated v wild-type), IDH2 (R140 or R172 mutated v wild-type), ASXL1 (mutated v wild-type), RUNX1 (mutated v wild-type), BAALC expression (high v low), platelets (continuous, 50-unit increase), and WBC count (continuous, 50-unit increase); for DFS, weighted summary score (high v low), FLT3-ITD (present v absent), FLT3-TKD (present v absent), ASXL1 (mutated v wild-type), DNMT3A (R882 mutated v non-R882 mutated or wild-type), RUNX1 (mutated v wild-type), ERG expression (high v low), BAALC expression (high v low), age (continuous, 10-year increase), and sex (male v female); for OS, weighted summary score (high v low), NPM1 (mutated v wild-type), FLT3-ITD (present v absent), CEBPA (mutated v wild-type), ASXL1 (mutated v wild-type), DNMT3A (R882 mutated v non-R882 mutated or wild-type), RUNX1 (mutated v wild-type), ERG expression (high v low), BAALC expression (high v low), and platelets (continuous, 50-unit increase).
The weighted summary score is the Cox regression coefficient weighted sum of the median dichotomized values for the seven genes [weighted summary score = 0.71900(CD34) + 0.61927(MIR155HG) + 0.67258(RHOC) + 0.66929(SCRN1) + 0.65925(F2RL1) + 0.65777(FAM92A1) + 0.61491(VWA8)]. For each gene, high and low expression was based on the cohort-specific median cutoff. The weighted summary score was then dichotomized using a cohort-specific median cut to determine the low and high groups. An OR > 1 (< 1) corresponds to a higher (lower) odds of achieving a CR for the first level listed of a dichotomous variable. An HR > 1 corresponds to worse outcome for higher values of continuous variables and the first level listed of a dichotomous variable.