Prognostic thresholds for molecular MRD markers in AML patients who are in complete morphological remission
| Gene . | Number of patients . | Time point . | PB vs BM . | cDNA vs DNA . | Favorable prognostic cutoff (proportion of patients) . | Associated risk . | Sensitivity of the assay . | Reference . |
|---|---|---|---|---|---|---|---|---|
| NPM1 | 194 | After 2 cycles of chemotherapy | PB | cDNA | Negative (84.5%) | 3-y CIR 30% (vs 82% if positive), 3-y OS 75% (vs 24% if positive) | 10−5 (range, 10−3.7 to 10−7.1) | 60 |
| NPM1 | 137 | After 2 cycles of chemotherapy | BM | cDNA | Negative (19%) | 4-y CIR 6.4% (vs 53% if positive), 4-y OS 90% (vs 56% if positive) | 10−5 to 10−6 | 54 |
| NPM1 | 82 | After 2 cycles of chemotherapy | BM | cDNA | Negative (26%) | 3-y OS 84% (vs 76% if NPM1/ABL ≤1% vs 47% if NPM1/ABL >1%) | 53 | |
| NPM1 | 194 | At end of treatment | PB | cDNA | Negative (92%) | 3-y OS 80% (vs not estimable if positive) | 10−5 (range, 10−3.7 to 10−7.1) | 60 |
| NPM1 | 131 (for PB) | After 1 or 2 induction cycles | PB | cDNA | ≥4log10 reduction (55%) | 3-y CIR 20.5% (vs 65.8% if <4log10 reduction); 3-y OS 91%-93% (vs 40.8% if <4log10 reduction) | 0.01% | 78 |
| NPM1 | 129 | At end of treatment | BM | cDNA | Negative (48%) | 4-y CIR 15.7% (vs 66.5% if positive), 4-y OS 80% (vs 44% if positive) | 10−5 to 10−6 | 54 |
| NPM1 | 80 | At end of treatment | BM | cDNA | Negative (49%) | 1-y CIR 37% (vs 63% if NPM1/ABL ≤1% vs 85% if NPM1/ABL >1%); 2-y OS 82% (vs 61% if NPM1/ABL ≤1% vs 45% if NPM1/ABL >1%) | 10−5 | 53 |
| NPM1 | 136 | In follow-up | BM | cDNA | <200 copies (68% of patients completing chemotherapy) | No relapses occurred. | 10−5 to 10−6 | 54 |
| RUNX1-RUNX1T1 | 94 | At end of treatment | PB | cDNA | Negative (70%) | 4-y CIR 23.6% (vs 50.9% if positive), 4-y OS 96% (vs 63.6% if positive) | 10−5 | 73 |
| RUNX1-RUNX1T1 | 120 | At end of treatment | BM | cDNA | Negative (49%) | 4-y EFS 81% (vs 61% if positive), 4-y OS 93% (vs 67% if positive) | 10−6 | 72 |
| 94 | At end of treatment | BM | cDNA | Negative (30%) | 4-y CIR 28.2% (vs 33.8% if positive), 4-y OS 86.4% (vs 87.7% if positive, n.s.) | 10−5 | 73 | |
| RUNX1-RUNX1T1 | 163 | In follow-up | PB | cDNA | <100 copies/105 ABL copies (85%) | 5-y CIR 7% (vs 100% if ≥100), 5-y OS 95% (vs 59% if ≥100) | 10−5 | 70 |
| RUNX1-RUNX1T1 | 163 | In follow-up | BM | cDNA | <500 copies/105 ABL copies (83.5%) | 5-y CIR 7% (vs 100% if ≥500), 5-y OS 94% (vs 57% if ≥500) | 10−5 | 70 |
| CBFB-MYH11 | 115 | At end of treatment | PB | cDNA | <10 copies/105 ABL copies (80%) | 5-y CIR 36% (vs 78% if ≥10) | 10−5 | 70 |
| CBFB-MYH11 | 115 | In follow-up | PB | cDNA | <10 copies/105 ABL copies (69%) | 5-y CIR 7% (vs 97% if ≥10), 5-y OS 91% (vs 57% if ≥10) | 10−5 | 70 |
| CBFB-MYH11 | 115 | In follow-up | BM | cDNA | <50 copies/105 ABL copies (73%) | 5-y CIR 10% (vs 100% if ≥50), 5-y OS 100% (vs 25% if ≥50) | 10−5 | 70 |
| PML-RARA | 301 | At end of treatment (ATRA + anthracycline based) | BM | cDNA | Negative (95%) | 3-y CIR 11% (vs 34% if positive) | At least 10−3 | 66 |
| PML-RARA | 115 | At end of treatment (ATO + ATRA, low and intermediate risk APL) | BM | cDNA | Negative (100%) | 4.2-y CIR 1.9% | n.d. | 67 |
| WT1 | 129 | After induction | PB or BM | cDNA | ≥2 log reduction in the same tissue (PB or BM) (62%) | 5-y CIR 40% (vs 75% if <2 log) | 10−4 | 45 |
| WT1 | 584 | At end of treatment | BM | cDNA | <10 copies (32%) | 3-y CIR 25% (vs 45% if 10-100 copies vs 72 of >100 copies), 3-y OS 72% (vs 59% if 10-100 copies vs 30% if >100 copies) | 10−4 | 46 |
| Gene . | Number of patients . | Time point . | PB vs BM . | cDNA vs DNA . | Favorable prognostic cutoff (proportion of patients) . | Associated risk . | Sensitivity of the assay . | Reference . |
|---|---|---|---|---|---|---|---|---|
| NPM1 | 194 | After 2 cycles of chemotherapy | PB | cDNA | Negative (84.5%) | 3-y CIR 30% (vs 82% if positive), 3-y OS 75% (vs 24% if positive) | 10−5 (range, 10−3.7 to 10−7.1) | 60 |
| NPM1 | 137 | After 2 cycles of chemotherapy | BM | cDNA | Negative (19%) | 4-y CIR 6.4% (vs 53% if positive), 4-y OS 90% (vs 56% if positive) | 10−5 to 10−6 | 54 |
| NPM1 | 82 | After 2 cycles of chemotherapy | BM | cDNA | Negative (26%) | 3-y OS 84% (vs 76% if NPM1/ABL ≤1% vs 47% if NPM1/ABL >1%) | 53 | |
| NPM1 | 194 | At end of treatment | PB | cDNA | Negative (92%) | 3-y OS 80% (vs not estimable if positive) | 10−5 (range, 10−3.7 to 10−7.1) | 60 |
| NPM1 | 131 (for PB) | After 1 or 2 induction cycles | PB | cDNA | ≥4log10 reduction (55%) | 3-y CIR 20.5% (vs 65.8% if <4log10 reduction); 3-y OS 91%-93% (vs 40.8% if <4log10 reduction) | 0.01% | 78 |
| NPM1 | 129 | At end of treatment | BM | cDNA | Negative (48%) | 4-y CIR 15.7% (vs 66.5% if positive), 4-y OS 80% (vs 44% if positive) | 10−5 to 10−6 | 54 |
| NPM1 | 80 | At end of treatment | BM | cDNA | Negative (49%) | 1-y CIR 37% (vs 63% if NPM1/ABL ≤1% vs 85% if NPM1/ABL >1%); 2-y OS 82% (vs 61% if NPM1/ABL ≤1% vs 45% if NPM1/ABL >1%) | 10−5 | 53 |
| NPM1 | 136 | In follow-up | BM | cDNA | <200 copies (68% of patients completing chemotherapy) | No relapses occurred. | 10−5 to 10−6 | 54 |
| RUNX1-RUNX1T1 | 94 | At end of treatment | PB | cDNA | Negative (70%) | 4-y CIR 23.6% (vs 50.9% if positive), 4-y OS 96% (vs 63.6% if positive) | 10−5 | 73 |
| RUNX1-RUNX1T1 | 120 | At end of treatment | BM | cDNA | Negative (49%) | 4-y EFS 81% (vs 61% if positive), 4-y OS 93% (vs 67% if positive) | 10−6 | 72 |
| 94 | At end of treatment | BM | cDNA | Negative (30%) | 4-y CIR 28.2% (vs 33.8% if positive), 4-y OS 86.4% (vs 87.7% if positive, n.s.) | 10−5 | 73 | |
| RUNX1-RUNX1T1 | 163 | In follow-up | PB | cDNA | <100 copies/105 ABL copies (85%) | 5-y CIR 7% (vs 100% if ≥100), 5-y OS 95% (vs 59% if ≥100) | 10−5 | 70 |
| RUNX1-RUNX1T1 | 163 | In follow-up | BM | cDNA | <500 copies/105 ABL copies (83.5%) | 5-y CIR 7% (vs 100% if ≥500), 5-y OS 94% (vs 57% if ≥500) | 10−5 | 70 |
| CBFB-MYH11 | 115 | At end of treatment | PB | cDNA | <10 copies/105 ABL copies (80%) | 5-y CIR 36% (vs 78% if ≥10) | 10−5 | 70 |
| CBFB-MYH11 | 115 | In follow-up | PB | cDNA | <10 copies/105 ABL copies (69%) | 5-y CIR 7% (vs 97% if ≥10), 5-y OS 91% (vs 57% if ≥10) | 10−5 | 70 |
| CBFB-MYH11 | 115 | In follow-up | BM | cDNA | <50 copies/105 ABL copies (73%) | 5-y CIR 10% (vs 100% if ≥50), 5-y OS 100% (vs 25% if ≥50) | 10−5 | 70 |
| PML-RARA | 301 | At end of treatment (ATRA + anthracycline based) | BM | cDNA | Negative (95%) | 3-y CIR 11% (vs 34% if positive) | At least 10−3 | 66 |
| PML-RARA | 115 | At end of treatment (ATO + ATRA, low and intermediate risk APL) | BM | cDNA | Negative (100%) | 4.2-y CIR 1.9% | n.d. | 67 |
| WT1 | 129 | After induction | PB or BM | cDNA | ≥2 log reduction in the same tissue (PB or BM) (62%) | 5-y CIR 40% (vs 75% if <2 log) | 10−4 | 45 |
| WT1 | 584 | At end of treatment | BM | cDNA | <10 copies (32%) | 3-y CIR 25% (vs 45% if 10-100 copies vs 72 of >100 copies), 3-y OS 72% (vs 59% if 10-100 copies vs 30% if >100 copies) | 10−4 | 46 |
APL, acute promyelocytic leukemia; ATO, arsenic trioxide; ATRA, all-trans retinoic acid; n.s., not significant.