Machine learning derived genomics driven prognostication for acute myeloid leukemia with RUNX1-RUNX1T1

Figures & data

Table 1. Prognostic significance of machine learning derived genetic risk in AML with t(8;21).

Parameter			Observation (%)
Demographics:
Age			Range: 2–60 years; Median: 20 years
Sex			Male:Female : 2.2:1
Clinical characteristics:
Total number of patients accrued			131
Cases not in morphological remission			13
Remission characteristics:
Complete remission (CR)			50
CR with incomplete hematologic recovery (CRi)			81
Bone marrow transplantation:
Patients who underwent BMT			04
Laboratory characteristics:
Blood counts at presentation
1. More than 50,000/mm^3			08
2. Less than 50,000/mm^3			123
Individual parameters of genetic risk score:
1. Mutation burden (≥2)			53 (40.4%)
2. Any KIT mutation			44 (33.5%)
3. NRAS mutation			25 (19.1%)
4. RAD21 mutation			11 (8.4%)
5. Any FLT3 mutation			11 (8.4%)
6. ASXL2 mutation			17 (13%)
Classification according to genetic risk:
Favorable genetic risk (Fav GR)			63 (48.1%)
Poor genetic risk (Poor GR)			68 (51.9%)
Post induction flow MRD (n = 131):
MRD positive			58 (44.2%)
MRD negative			73 (55.7%)
Post consolidation flow MRD (n = 99):
MRD positive			13 (13.1%)
MRD negative			86 (86.8%)
Paired MRD analysis (n = 87):
Any MRD positive			46 (52.8%)
Dual time point MRD negative			41 (47.1%)
Univariate Cox analysis
Machine learning derived genetic risk	Overall survival (OS)		Relapse free survival (RFS)
	HR (95% CI)	p	HR (95% CI)	p
Favorable genetic risk	1	0.0001	1	0.0008
Poor genetic risk	3.5 (1.88–6.55)		2.5 (1.43–4.33)
Machine learning derived	Overall survival (OS)		Relapse free survival (RFS)
genetic risk	HR (95% CI)	p	HR (95% CI)	p
Favorable genetic risk	Mean OS: 44.6 months; 95% CI (40.6–48.6 months), Median OS: not reached	0.0001	Mean RFS: 37.7 months; 95% CI (32.8–42.6 months), Median RFS: 72.6 months 95% CI (35.1–72.6 months)	0.0008
Poor genetic risk	Mean OS: 29.6 months; 95% CI (23.7–35.6 months), Median OS: 30.5 months; 95% CI (16.0–42.1 months)		Mean RFS: 24.4 months; 95% CI (19.0–29.9 months), Median RFS: 16.7 months; 95% CI (12.7–32.6 months)
Dual time point FCM-MRD	Overall survival (OS)		Relapse free survival (RFS)
	HR (95% CI)	p	HR (95% CI)	p
MRD Negative	1	0.01	1	0.01
MRD Positive	2.5 (1.16–5.50)		1.6 (0.87–3.18)
Dual time point FCM-MRD	Overall survival (OS)		Relapse free survival (RFS)
	HR (95% CI)	p	HR (95% CI)	p
MRD Negative	Mean OS: 62.8 months; 95% CI (53.1–72.4 months), Median OS: 74.1 months; 95% CI (74.1–74.1 months)	0.01	Mean RFS: 49.5 months; 95% CI (39.4–59.7 months), Median RFS: 72.6 months 95% CI (29.2–72.6 months)	0.01
MRD Positive	Mean OS: 52.9 months; 95% CI (40.3–65.4 months), Median OS: not reached		Mean RFS: 43.0 months; 95% CI (30.3–55.7 months), Median RFS: 23.5 months; 95% CI (15.4–32.6 months)
	Overall survival (OS)		Relapse free survival (RFS)
Multivariate cox analysis	HR (95% CI)	p	HR (95% CI)	p
Dual MRD positive	1.6 (0.77–3.47)	0.202	1.3 (0.67–2.58)	0.41
Poor genetic risk	3.7 (1.69–8.08)	0.001	2.3 (1.17–4.60)	0.01

OS: Overall Survival; RFS: Relapse Free Survival; HR: Hazards ratio; CI: confidence interval; MRD: Measurable Residual Disease. FCM-MRD was assessed in 87 patients in morphological CR (<5% blasts).

Figure 1. The above circos plot (A) highlights the spectrum of mutations and their interaction in AML with RUNX1-RUNX1T1. Commonly occurring gene mutations are colored. The machine learning derived scoring system is described in (B). The Kaplan–Meier plot in the top right section (C) shows the clinical impact on overall survival (OS) and for relapse free survival (RFS, D), lower right).