Table 1. Key studies on the prognostic... | American Society of Hematology

Table 1.

Key studies on the prognostic value of MRD by MFC

Reference	Multicenter, yes/no	Study population, adult/children	% LAIP	Number of patients	MRD measurement following	Cutoff MRD level			Univariate analysis significant for	Multivariate analysis significant for	Study details
Reference	Multicenter, yes/no	Study population, adult/children	% LAIP	Number of patients	MRD measurement following	I	C	Post-Tx	Univariate analysis significant for	Multivariate analysis significant for	Study details
81	N	A	46	53	I, C	<0.05%	0.2%		RFS, OS	RFS
82	Y	A	70	56	I, C	0.045%	0.035%		I;-C: RFS, OS	I:-C: RFS, OS
83		A	75	126	I	<0.01%,	-		RFS, OS	RFS	MRD >1%: 3 y RR: 85%
						0.01%-0.1%	-				MRD 0.1%-1.0%: 3 y RR: 45%
						0.1%-1%	-				MRD 0.01%-0.1%: 3 y RR: 14%
						>1%	-				MRD < 0.01%: 3 y RR: 0%
84	Y	Ch	?	252	I₁	0.5%			RFS, OS	RFS, OS	3 y OS 69% (MRD neg) vs 41% (MRD pos)
85	Y	A	100	106	Day 16	Log difference 2.11			CR, EFS, RFS, OS	EFS, RFS
86	N	A	100	62	I, C	Log difference 2.11	Log difference 2.53		I: RFS C: RFS, OS	I: RFS C: RFS
34	N	A	100	72	I₁, I₂, C, PBSCT	I₁: 1% I₂: 0.14%	0.11%	0.13%	I₁, I₂, C, PBSCT; RFS, OS	I₁, I₂, C, PBSCT; RFS, OS
87	Y	A	89	100	I, C	0.035%	0.035%		I and C: RR, RFS, OS	I:-C: RR, RFS, OS	5 y RFS 72% (MRD neg) vs 11% (MRD pos)
88	Y	A, Ch	?	150	Day 15, I, I₂, C	0.1%-2%	0.1%-1.3%		Day 15, I; RFS	—	MRD similar EFS as traditional risk factors
89	Y	A	?	142	I, C	0.035%	0.035%		I and C: RFS, OS	I and C: RFS, OS	5 y RR 60% (MRD pos) vs 16% (MRD neg)
90	N	A	94	54	I, C	0.15%	0.15%		I: RFS, OS	I: RFS, OS
90	N	A	94	54	I, C	0.15%	0.15%		C: RFS,OS	C:-
91	Y	Ch	?	94	I₁, I₂, C, end of Tx	<0.1%			I₁: RFS, OS	I₁: RFS, OS	3 y RFS 64% (MRD pos) vs 14% (MRD neg)
						0.1%-0.5%
						>0.5%
61	Y	Ch	100	188	I₁, I₂, end of Tx	>0%, 0-1%			I₁: OS, RFS	I₁: OS, RFS	RR at 3 y 60% vs 29%
61	Y	Ch	100	188	I₁, I₂, end of Tx	>0%, 0-1%			I₂: RFS, OS	I₂: RFS, RR	RR at 3 y 60% vs 29%
62	Y	Ch	?	203	I₁, I₂, end of Tx		<0.1%		I₁: EFS, RFS	I₁: EFS, RFS	Morphological assessment has limited value in comparison with flow cytometry.
							0.1%-1%		I₂: EFS, RFS	I₂: EFS, RFS
							>1%
28	Y	A	89	517	I₁, I₂,	<0.1%	<0.1%		I₁: RFS, OS	I₁: RFS, OS	Cutoff points between 0.05 and 0.8 are all significant.
28	Y	A	89	517	I₁, I₂,	<0.1%	<0.1%		I₂: RFS, OS	I₂: RFS, OS	Cutoff points between 0.05 and 0.8 are all significant.
30	Y	A	93	427	I₁, I₂,	<0.1%	<0.1%			I₁: RFS, OS	3 y OS 38% (MRD pos) vs 18% (MRD neg) after cycle 2
30	Y	A	93	427	I₁, I₂,	<0.1%	<0.1%			I₂: RFS, OS	3 y OS 38% (MRD pos) vs 18% (MRD neg) after cycle 2
32	N	A, Ch	100	253	Pre-Tx	<0.1%			DFS		MRD predictive in CR1 and CR2
32	N	A, Ch	100	253	Pre-Tx	<0.1%			OS		MRD predictive in CR1 and CR2
92	Y	A	?	210	I, C	0.035%	0.035%		I, C: DFS, OS	I, C: DFS, OS	MRD negativity gives 5 y DFS: 57 vs 13% in elderly AML
76	N	A	100	359	Pre-Tx	0.1%				OS, PFS, RFS	3 y RR 67% (MRD pos) vs 22% (MRD neg)
93	Y	A	100	306	At the time of morphological CR	<0.01%			RFS	RFS	Multivariate analysis revealed MRD, age. and cytogenetics as independent variables. Cytogenetics and MRD are complementary in a scoring system.
						0.01%-0.1%
						>0.1%
94	Y	Ch	78	101	Day 15, pre-C	0.1%	0.1%		Day 15: EFS, OS	Day 15: EFS, OS	EFS at 5 y 65% (MRD neg) vs 22% (MRD pos)
94	Y	Ch	78	101	Day 15, pre-C	0.1%	0.1%		Pre-C: EFS, OS	Pre-C: EFS, OS	EFS at 5 y 65% (MRD neg) vs 22% (MRD pos)
95	Y	Ch (1-21 y)	?	216	I₁, I₂	<0.1%,	-		EFS	I₁, I₂: EFS	I₁: CIR at 3 y 38.6% for MRD pos and 16.9% for MTD neg
						0.1%-1%	-		OS	I₁, I₂: OS	I₂: 56.3% vs 16.7%
						>1%
96	N	A	100	241	Pre-Tx	0.1%			DFS, OS, relapse	DFS, OS, relapse	Negative impact of MRD on posttransplant MRD is similar after NMA and MA conditioning.

Reference	Multicenter, yes/no	Study population, adult/children	% LAIP	Number of patients	MRD measurement following	Cutoff MRD level			Univariate analysis significant for	Multivariate analysis significant for	Study details
Reference	Multicenter, yes/no	Study population, adult/children	% LAIP	Number of patients	MRD measurement following	I	C	Post-Tx	Univariate analysis significant for	Multivariate analysis significant for	Study details
81	N	A	46	53	I, C	<0.05%	0.2%		RFS, OS	RFS
82	Y	A	70	56	I, C	0.045%	0.035%		I;-C: RFS, OS	I:-C: RFS, OS
83		A	75	126	I	<0.01%,	-		RFS, OS	RFS	MRD >1%: 3 y RR: 85%
						0.01%-0.1%	-				MRD 0.1%-1.0%: 3 y RR: 45%
						0.1%-1%	-				MRD 0.01%-0.1%: 3 y RR: 14%
						>1%	-				MRD < 0.01%: 3 y RR: 0%
84	Y	Ch	?	252	I₁	0.5%			RFS, OS	RFS, OS	3 y OS 69% (MRD neg) vs 41% (MRD pos)
85	Y	A	100	106	Day 16	Log difference 2.11			CR, EFS, RFS, OS	EFS, RFS
86	N	A	100	62	I, C	Log difference 2.11	Log difference 2.53		I: RFS C: RFS, OS	I: RFS C: RFS
34	N	A	100	72	I₁, I₂, C, PBSCT	I₁: 1% I₂: 0.14%	0.11%	0.13%	I₁, I₂, C, PBSCT; RFS, OS	I₁, I₂, C, PBSCT; RFS, OS
87	Y	A	89	100	I, C	0.035%	0.035%		I and C: RR, RFS, OS	I:-C: RR, RFS, OS	5 y RFS 72% (MRD neg) vs 11% (MRD pos)
88	Y	A, Ch	?	150	Day 15, I, I₂, C	0.1%-2%	0.1%-1.3%		Day 15, I; RFS	—	MRD similar EFS as traditional risk factors
89	Y	A	?	142	I, C	0.035%	0.035%		I and C: RFS, OS	I and C: RFS, OS	5 y RR 60% (MRD pos) vs 16% (MRD neg)
90	N	A	94	54	I, C	0.15%	0.15%		I: RFS, OS	I: RFS, OS
90	N	A	94	54	I, C	0.15%	0.15%		C: RFS,OS	C:-
91	Y	Ch	?	94	I₁, I₂, C, end of Tx	<0.1%			I₁: RFS, OS	I₁: RFS, OS	3 y RFS 64% (MRD pos) vs 14% (MRD neg)
						0.1%-0.5%
						>0.5%
61	Y	Ch	100	188	I₁, I₂, end of Tx	>0%, 0-1%			I₁: OS, RFS	I₁: OS, RFS	RR at 3 y 60% vs 29%
61	Y	Ch	100	188	I₁, I₂, end of Tx	>0%, 0-1%			I₂: RFS, OS	I₂: RFS, RR	RR at 3 y 60% vs 29%
62	Y	Ch	?	203	I₁, I₂, end of Tx		<0.1%		I₁: EFS, RFS	I₁: EFS, RFS	Morphological assessment has limited value in comparison with flow cytometry.
							0.1%-1%		I₂: EFS, RFS	I₂: EFS, RFS
							>1%
28	Y	A	89	517	I₁, I₂,	<0.1%	<0.1%		I₁: RFS, OS	I₁: RFS, OS	Cutoff points between 0.05 and 0.8 are all significant.
28	Y	A	89	517	I₁, I₂,	<0.1%	<0.1%		I₂: RFS, OS	I₂: RFS, OS	Cutoff points between 0.05 and 0.8 are all significant.
30	Y	A	93	427	I₁, I₂,	<0.1%	<0.1%			I₁: RFS, OS	3 y OS 38% (MRD pos) vs 18% (MRD neg) after cycle 2
30	Y	A	93	427	I₁, I₂,	<0.1%	<0.1%			I₂: RFS, OS	3 y OS 38% (MRD pos) vs 18% (MRD neg) after cycle 2
32	N	A, Ch	100	253	Pre-Tx	<0.1%			DFS		MRD predictive in CR1 and CR2
32	N	A, Ch	100	253	Pre-Tx	<0.1%			OS		MRD predictive in CR1 and CR2
92	Y	A	?	210	I, C	0.035%	0.035%		I, C: DFS, OS	I, C: DFS, OS	MRD negativity gives 5 y DFS: 57 vs 13% in elderly AML
76	N	A	100	359	Pre-Tx	0.1%				OS, PFS, RFS	3 y RR 67% (MRD pos) vs 22% (MRD neg)
93	Y	A	100	306	At the time of morphological CR	<0.01%			RFS	RFS	Multivariate analysis revealed MRD, age. and cytogenetics as independent variables. Cytogenetics and MRD are complementary in a scoring system.
						0.01%-0.1%
						>0.1%
94	Y	Ch	78	101	Day 15, pre-C	0.1%	0.1%		Day 15: EFS, OS	Day 15: EFS, OS	EFS at 5 y 65% (MRD neg) vs 22% (MRD pos)
94	Y	Ch	78	101	Day 15, pre-C	0.1%	0.1%		Pre-C: EFS, OS	Pre-C: EFS, OS	EFS at 5 y 65% (MRD neg) vs 22% (MRD pos)
95	Y	Ch (1-21 y)	?	216	I₁, I₂	<0.1%,	-		EFS	I₁, I₂: EFS	I₁: CIR at 3 y 38.6% for MRD pos and 16.9% for MTD neg
						0.1%-1%	-		OS	I₁, I₂: OS	I₂: 56.3% vs 16.7%
						>1%
96	N	A	100	241	Pre-Tx	0.1%			DFS, OS, relapse	DFS, OS, relapse	Negative impact of MRD on posttransplant MRD is similar after NMA and MA conditioning.

Adapted from Ossenkoppele and Schuurhuis.²⁹

?, not known; A, adult; C, consolidation; Ch, children; CIR, cumulative incidence of relapse; CR, complete remission; DFS, disease-free survival; EFS, event-free survival; I, induction treatment; I₁, induction cycle 1; I₂, induction cycle 2C; N, no; LAIP, leukemia-associated immunophenotype; MA, myeloablative; NMA, nonmyeloablative; OS, overall survival; PBSCT, peripheral blood stem cell transplantation; PFS, progression-free survival; RFS, relapse-free survival; RR, relapse risk; Tx, transplantation; Y, yes.

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