TABLE 1.

Summary of NGS-based multi-gene MRD studies in AML.

					Study	Mean	Maximum
					size	MRD	sensitivity
Author	Year	Key findings	Disease state	Technique	(n)	coverage	(VAF)
Klco	2015	Clearance of disease-specific mutations at 30 days post induction correlated with better EFS and OS	AML, post induction	WES or WGS, and amplicon-based sequencing with paired normal tissue	50	543X (exome) 14,780X (amplicon)	2.5%
Jongen- Lavrencic	2018	Persistence of non-“DTA” mutations correlated with decreased RFS and OS. Combining NGS and flow MRD data produced strong correlations with outcome when methods were concordant and defined an intermediate prognosis group when methods were discordant	AML, post induction	54 Gene tumor-only NGS panel with position-based error correction	482	Not stated	0.02%
Morita	2018	Patients with clearance of disease-associated mutations (<1% VAF) at 30 days post induction had better OS and better EFS after multivariate analysis; this correlation was strengthened by the exclusion of “DTA mutations” from the analysis	AML, post induction	295 Gene tumor only NGS panel	131	575X	<1.0%
Thol	2018	Detection of disease-associated mutations post-transplant was associated with higher incidence of relapse, but no difference in OS	AML, pre- transplant	46 Gene custom amplicon panel with UMI-based error correction	116	6,100x	0.02%
Kim	2018	MRD positive patients had a higher incidence of relapse and lower OS	AML, post-transplant	84 Gene NGS panel with paired normal T-cells and position-based error correction	104	1726X	0.02%
Balagopal	2019	Found evidence of MRD in 18/30 (60%) of post-transplant AML patients who showed no evidence of disease by standard engraftment studies	AML, post-transplant	22 Gene panel with UMI-based error correction	30	>10,000X	0.1%
Press	2019	NGS MRD positive pre-transplant patients had higher risk of relapse in multivariate analysis	AML, pre- transplant	42 Gene panel, coverage-based error correction	42	1900x	0.5%
Hourigan	2019	NGS MRD positive pre-transplant patients with reduced-intensity conditioning had increased relapse rates, decreased overall survival, and decreased OS compared to patients who underwent myeloablative conditioning	AML, pre- transplant	13 Gene panel with UMI-error correction run in peripheral blood samples.	190	>100,000x	0.001%

Abbreviations: EFS, event free survival; OS, overall survival; NGS, next generation sequencing; WES, whole exome sequencing; WGS, whole genome sequencing; RFS, relapse free survival; MRD, measurable residual disease; UMI, unique molecular identifier.