Table 2.

Clinical studies on the prognostic value of MRD in adult and childhood AML by MPFC

Ref.Multi- centerStudy pop.% LAIPNo. of ptsMRD measurement afterCutoff MRD levelUnivariate analysis significant forMultivariate analysis significant forStudy details
ICPost-Tx
44 N A 46 53 I, C 0.05% 0.2%  RFS, OS RFS  
45 Y A 70 56 I, C 0.045% 0.035%  I; -C: RFS, OS I: -C: RFS, OS  
46  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% 
47 N Ch 85 46 I1, I2 0.1%   I1: RR, OS I1: OS  
I2: RR, OS I2: OS 
48  A 79 31 Pre Tx  0.035%  RR after Tx   
15 Y Ch ? 252 I1 0.5%   RFS, OS RFS, OS 3-y OS 69% (MRD−) vs 41% (MRD+) 
49 Y A 100 106 Day 16 Log diff.   CR, EFS, RFS, OS EFS, RFS  
2.11   
50 N A 100 62 I, C Log diff. Log diff.  I: RFS I: RFS  
2.11 2.53 C: RFS, OS C: RFS 
51 N A 100 72 I1, I2, C, PBSCT I1: 1% 0.11% 0.13% I1, I2, C, PBSCT; RFS, OS I1, I2, C, PBSCT; RFS, OS  
I2: 0.14%   
52* A A 89 100 I, C 0.035% 0.035%  I and C: I: -C: RR, RFS, OS 5-y RFS 72% (MRD−) vs 11% (MRD+) 
RR, RFS, OS 
53 N A 94 45 I, C 0.05%-0.1% 0.05%-0.1%  I: RFS C: RFS  5-y RFS 85% (MRD−) vs 42% (MRD+) 
54 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 
55 N A ? 41 Day after Tx   0.1% RFS, OS RFS, OS   
56 Y A ? 142 I, C 0.035% 0.035%  I and C; RFS, OS I and C; RFS, OS 5-y RR 60% (MRD+) vs 16% (MRD−)  
57 N A 94 54 I, C 0.15% 0.15%  I: RFS, OS I: RFS, OS   
C: RFS, OS C: -  
58 Y Ch ? 94 I1, I2, C, end of Tx <0.1%   I1: RFS, OS I1: RFS, OS 3-y RFS 64% (MRD+) vs 14% (MRD−)  
0.1%-0.5%    
>0.5%    
14 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%  
I2: RFS, OS I2: RFS, RR  
7 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%      
16 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.  
I2: RFS, OS I2: RFS, OS  
38 Y A 93 427 I1, I2, 0.1% 0.1%   I1: RFS, OS 3-y OS 38% (MRD+) vs 18% (MRD−) after cycle 2  
I2: RFS, OS  
39 N A, Ch 100 253 Pre Tx 0.1%     MRD predictive in CR1 and CR2  
59 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  
60 N A 100 359 Pre Tx 0.1%    OS, PFS, RFS 3-y RR 67% (MRD+) vs 22% (MRD−)  
61 Y A 100 306 At the time of morphologic 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%     
62 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−) vs 22% (MRD+)  
Pre C: EFS, OS Pre C: EFS, OS  
Ref.Multi- centerStudy pop.% LAIPNo. of ptsMRD measurement afterCutoff MRD levelUnivariate analysis significant forMultivariate analysis significant forStudy details
ICPost-Tx
44 N A 46 53 I, C 0.05% 0.2%  RFS, OS RFS  
45 Y A 70 56 I, C 0.045% 0.035%  I; -C: RFS, OS I: -C: RFS, OS  
46  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% 
47 N Ch 85 46 I1, I2 0.1%   I1: RR, OS I1: OS  
I2: RR, OS I2: OS 
48  A 79 31 Pre Tx  0.035%  RR after Tx   
15 Y Ch ? 252 I1 0.5%   RFS, OS RFS, OS 3-y OS 69% (MRD−) vs 41% (MRD+) 
49 Y A 100 106 Day 16 Log diff.   CR, EFS, RFS, OS EFS, RFS  
2.11   
50 N A 100 62 I, C Log diff. Log diff.  I: RFS I: RFS  
2.11 2.53 C: RFS, OS C: RFS 
51 N A 100 72 I1, I2, C, PBSCT I1: 1% 0.11% 0.13% I1, I2, C, PBSCT; RFS, OS I1, I2, C, PBSCT; RFS, OS  
I2: 0.14%   
52* A A 89 100 I, C 0.035% 0.035%  I and C: I: -C: RR, RFS, OS 5-y RFS 72% (MRD−) vs 11% (MRD+) 
RR, RFS, OS 
53 N A 94 45 I, C 0.05%-0.1% 0.05%-0.1%  I: RFS C: RFS  5-y RFS 85% (MRD−) vs 42% (MRD+) 
54 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 
55 N A ? 41 Day after Tx   0.1% RFS, OS RFS, OS   
56 Y A ? 142 I, C 0.035% 0.035%  I and C; RFS, OS I and C; RFS, OS 5-y RR 60% (MRD+) vs 16% (MRD−)  
57 N A 94 54 I, C 0.15% 0.15%  I: RFS, OS I: RFS, OS   
C: RFS, OS C: -  
58 Y Ch ? 94 I1, I2, C, end of Tx <0.1%   I1: RFS, OS I1: RFS, OS 3-y RFS 64% (MRD+) vs 14% (MRD−)  
0.1%-0.5%    
>0.5%    
14 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%  
I2: RFS, OS I2: RFS, RR  
7 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%      
16 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.  
I2: RFS, OS I2: RFS, OS  
38 Y A 93 427 I1, I2, 0.1% 0.1%   I1: RFS, OS 3-y OS 38% (MRD+) vs 18% (MRD−) after cycle 2  
I2: RFS, OS  
39 N A, Ch 100 253 Pre Tx 0.1%     MRD predictive in CR1 and CR2  
59 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  
60 N A 100 359 Pre Tx 0.1%    OS, PFS, RFS 3-y RR 67% (MRD+) vs 22% (MRD−)  
61 Y A 100 306 At the time of morphologic 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%     
62 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−) vs 22% (MRD+)  
Pre C: EFS, OS Pre C: EFS, OS  

?, not known; A, adult; C, consolidation; Ch, children; DFS, disease-free survival; diff., difference; I, induction treatment; I1, induction cycle 1; I2, induction cycle 2C; N, no; PBSCT, peripheral blood stem cell transplantation; Pop., population; pts, patients; Ref., reference; RR, relapse risk; Tx, transplantation; Y, yes.

*

Includes 56 patients previously reported by Venditti et al.45 

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