Table 3.
Evolution in risk of fusion-based groups over time and our proposed cytogenetic risk-group stratification of childhood KMT2A-r AML
| Fusion-based group | Balgobind et al 20092 |
Pollard et al 20214 |
van Weelderen et al 2024 |
||||||
|---|---|---|---|---|---|---|---|---|---|
| No. | 5-y pEFS (%) | Risk-group | No. | 5-y pEFS (%) | Risk-group | No. | 5-y pEFS (%) | Risk-group | |
| 1q21/KMT2A::MLLT11 | 24 | 92 | Favorable∗ | 5 | 60 | Intermediate | 27 | 55 | Intermediate |
| 9p22/KMT2A::MLLT3 | 321 | 50 | Intermediate | 82 | 49 | Intermediate | 512 | 54 | Intermediate |
| Non–FAB-M5 | 59 | 31 | Adverse | ND | ND | ND | 81 | 38 | Adverse |
| FAB-M5 | 254 | 59 | Intermediate† | ND | ND | ND | 298 | 66 | Intermediate† |
| FAB-M5/no trisomy 6 | ND | ND | ND | ND | ND | ND | 273 | 68 | Intermediate |
| FAB-M5/trisomy 6 | ND | ND | ND | ND | ND | ND | 11 | 29‡ | Adverse§ |
| Non–FAB-M5/no trisomy 6 | ND | ND | ND | ND | ND | ND | 66 | 39 | Adverse§ |
| Non–FAB-M5/trisomy 6 | ND | ND | ND | ND | ND | ND | 10 | 27 | Adverse§ |
| 19p13 | 31 | 49 | Intermediate | ND | ND | ND | 20 | 42 | Intermediate |
| 19p13.1/KMT2A::ELL | 33 | 46 | Intermediate | 15 | 65 | Intermediate | 71 | 45 | Intermediate |
| 19p13.3/KMT2A::MLLT1 | 23 | 46 | Intermediate | 7 | 14 | Adverse‖ | 55 | 35 | Adverse∗ |
| 17q21 | 12 | 42 | Intermediate | ND | ND | ND | 12 | 67 | Intermediate |
| 10p12/KMT2A::MLLT10 | 97 | 31 | Adverse∗ | 40 | 20 | Adverse‖ | 212 | 33 | Adverse∗ |
| 4q21/KMT2A::AFF1 | 13 | 29 | Adverse | 2 | 0 | Adverse‖ | 12 | 25 | Adverse∗ |
| 10p11.2/KMT2A::ABI1 | 12 | 17 | Adverse∗ | 6 | 17 | Adverse‖ | 24 | 22 | Adverse∗ |
| 6q27/KMT2A::AFDN | 35 | 11 | Adverse∗ | 15 | 15 | Adverse‖ | 89 | 23 | Adverse∗ |
| Xq24/KMT2A::SEPT6 | ND | ND | ND | 5 | 80 | Intermediate | 21 | 76 | Intermediate |
| 1p32/KMT2A::EPS15 | ND | ND | ND | ND | ND | ND | 12 | 75 | Intermediate |
| 17q12 | ND | ND | ND | ND | ND | ND | 10 | 56 | Intermediate |
Risk-group assignment was determined arbitrarily according to the EFS rate. Fusion-based groups with an EFS rate of <40% were classified as adverse-risk, whereas those with an EFS rate >40% were designated at intermediate risk. Furthermore, fusion-based groups with an EFS rate >75%, which demonstrated an independent association with superior EFS compared with patients with 9p22/KMT2A::MLLT3, were considered favorable risk. 9p22/KMT2A::MLLT3 refers to t(9;11)(p22;q23), 10p12/KMT2A::MLLT10 to t(10;11)(p12;q23), 6q27/KMT2A::AFDN to t(6;11)(q27;q23), 19p13.1/KMT2A::ELL to t(11;19)(q23;p13.1), 19p13.3/KMT2A::MLLT1 to t(11;19)(q23;p13.3), 1q21/KMT2A::MLLT11 to t(1;11)(q21;q23), 10p11.2/KMT2A::ABI1 to t(10;11)(p11.2;q23), 19p13 to t(11;19)(q23;p13) without ascertained subband, Xq24/KMT2A::SEPT6 to t(X;11)(q24;q23), 17q21 to t(11;17)(q23;q21), 1p32/KMT2A::EPS15 to t(1;11)(p32;q23), 4q21/KMT2A::AFF1 to t(4;11)(q21;q23), and 17q12 to t(11;17)(q23;q12).
Independently associated with superior/inferior EFS compared with patients with 9p22/KMT2A::MLLT3.
Independently associated with superior EFS compared with patients with 9p22/KMT2A::MLLT3 with non–FAB-M5 morphology.
For patients with FAB-M5 morphology with trisomy 6, the 3-year pEFS is shown because this estimate could not be extrapolated to 5 years.
Independently associated with inferior EFS compared with patients with 9p22/KMT2A::MLLT3 with FAB-M5 morphology and without trisomy 6.
In the study by Pollard et al,4 these 5 fusion-based groups were clustered into a high-risk cohort, which was independently associated with inferior EFS compared with the non–high-risk cohort.