AML risk stratification models utilizing ELN-2017 guidelines and additional prognostic factors: a SWOG report

Pogosova-Agadjanyan, Era L.; Moseley, Anna; Othus, Megan; Appelbaum, Frederick R.; Chauncey, Thomas R.; Chen, I-Ming L.; Erba, Harry P.; Godwin, John E.; Jenkins, Isaac C.; Fang, Min; Huynh, Mike; Kopecky, Kenneth J.; List, Alan F.; Naru, Jasmine; Radich, Jerald P.; Stevens, Emily; Willborg, Brooke E.; Willman, Cheryl L.; Wood, Brent L.; Zhang, Qing; Meshinchi, Soheil; Stirewalt, Derek L.

doi:10.1186/s40364-020-00208-1

Biomarker Research

Table 1 Genomic and transcript biomarkers significant in the discovery cohort

From: AML risk stratification models utilizing ELN-2017 guidelines and additional prognostic factors: a SWOG report

Variable		Cell Population
Biomarker	Value	MNCs		Blasts
Complete Response, CR		OR (95% CI)	P	OR (95% CI)	P
FLT3-ITD AR	Continuous	0.61 (0.27–1.36)	0.229	0.92 (0.75–1.14)	0.446
FLT3-ITD AR	≥ 0.5 vs. < 0.5	1.15 (0.38–3.51)	0.801	0.83 (0.24–2.84)	0.770
NPM1	Mutated vs. not	1.38 (0.74–2.59)	0.310	1.43 (0.76–2.72)	0.270
ERG1	Cont.	0.94 (0.88–1.00)	0.042	0.94 (0.90–0.99)	0.018
ERG1	IQR	0.73 (0.54–0.99)	0.042	0.63 (0.43–0.93)	0.018
EVI1	Binary	0.46 (0.24–0.89)	0.020	0.38 (0.19–0.76)	0.006
	Cont.	0.99 (0.98–1.00)	0.196	0.99 (0.98–1.01)	0.257
	IQR	1.00 (1.00–1.00)	0.196	1.00 (1.00–1.00)	0.257
KIT	Cont.	0.96 (0.91–1.01)	0.145	0.94 (0.88–0.99)	0.022
KIT	IQR	0.84 (0.67–1.06)	0.145	0.73 (0.56–0.95)	0.022
MN1	Cont.	0.99 (0.98–1.00)	0.064	0.99 (0.98–1.00)	0.020
MN1	IQR	0.86 (0.73–1.01)	0.064	0.78 (0.63–0.96)	0.020
Overall Survival, OS		HR (95% CI)	P	HR (95% CI)	P
FLT3-ITD AR	Continuous	1.45 (1.03–2.06)	0.035	1.08 (0.98–1.19)	0.133
FLT3-ITD AR	≥ 0.5 vs. < 0.5	1.05 (0.56–1.97)	0.879	0.92 (0.47–1.81)	0.807
NPM1	Mutated vs. not	1.10 (0.77–1.57)	0.610	1.04 (0.73–1.50)	0.820
CCNA1	Cont.	1.00 (1.00–1.00)	< 0.001	1.00 (1.00–1.00)	0.020
CCNA1	IQR	1.08 (1.03–1.14)	< 0.001	1.07 (1.01–1.13)	0.020
ERG1	Cont.	1.04 (1.01–1.07)	0.020	1.04 (1.01–1.07)	0.002
ERG1	IQR	1.21 (1.03–1.41)	0.020	1.36 (1.12–1.64)	0.002
EVI1	Binary	1.59 (1.10–2.29)	0.014	2.03 (1.39–2.96)	< 0.001
	Cont.	1.01 (1.00–1.01)	0.017	1.01 (1.00–1.01)	0.004
	IQR	1.00 (1.00–1.00)	0.017	1.00 (1.00–1.00)	0.004
FLT3	Cont.	1.02 (1.00–1.03)	0.013	1.02 (1.00–1.03)	0.026
FLT3	IQR	1.14 (1.03–1.27)	0.013	1.13 (1.01–1.26)	0.026
IL3RA	Cont.	1.02 (0.99–1.05)	0.128	1.03 (1.00–1.06)	0.044
IL3RA	IQR	1.08 (0.98–1.19)	0.128	1.11 (1.00–1.22)	0.044
Relapse-Free Survival, RFS		HR (95% CI)	P	HR (95% CI)	P
FLT3-ITD AR	Continuous	0.99 (0.30–3.30)	0.983	1.19 (0.92–1.55)	0.187
FLT3-ITD AR	≥ 0.5 vs. < 0.5	0.88 (0.40–1.94)	0.750	1.95 (0.77–4.94)	0.161
NPM1	Mutated vs. not	0.96 (0.60–1.52)	0.850	0.96 (0.59–1.54)	0.860
CCNA1	Cont.	1.00 (1.00–1.01)	0.004	1.00 (1.00–1.00)	0.083
CCNA1	IQR	1.20 (1.06–1.36)	0.004	1.10 (0.99–1.22)	0.083
EVI1	Binary	1.89 (1.14–3.13)	0.014	1.94 (1.13–3.32)	0.015
	Cont.	1.01 (1.00–1.02)	0.004	1.02 (1.01–1.03)	0.003
	IQR	1.00 (1.00–1.00)	0.004	1.00 (1.00–1.00)	0.003
IL3RA	Cont.	1.02 (1.00–1.05)	0.092	1.03 (1.00–1.07)	0.050
IL3RA	IQR	1.09 (0.99–1.21)	0.092	1.12 (1.00–1.25)	0.050

FLT3-ITD AR was analyzed both as a continuous variable (Cont.) and as a binary variable as defined by the ELN-2017 guidelines (≥0.5 vs. < 0.5). Transcript expression fold changes were analyzed both as unadjusted variables (Cont.) and adjusted (divided) by the interquartile range (IQR) of the corresponding expression variable in the discovery data. EVI1 was analyzed as a continuous and as a binary variable (expressed vs. not)

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