Risk status stratification by genetic abnormality per ELN 2017 and NCCN 2017 guidelines
| Risk category* . | ELN criteria10 . | NCCN criteria6 . |
|---|---|---|
| Favorable | t(8;21)(q22;q22.1); RUNX1-RUNX1T1 | Core binding factor: inv(16)†,‡ or t(16;16)†,‡ or t(8;21)†,‡ or t(15;17)‡ |
| inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11 | Normal cytogenetics: NPM1 mutation in absence of FLT3-ITD or isolated biallelic (double) CEBPA mutation | |
| Mutated NPM1 without FLT3-ITD or with FLT3-ITDlow§ | ||
| Biallelic mutated CEBPA | ||
| Intermediate | Mutated NPM1 and FLT3-ITDhigh§ | Normal cytogenetics |
| Wild-type NPM1 without FLT3-ITD or with FLT3-ITDlow§ (without adverse-risk genetic lesions) | +8 alone | |
| t(9;11)(p21.3;q23.3); MLLT3-KMT2A|| | t(9;11) | |
| Cytogenetic abnormalities not classified as favorable or adverse | Other nondefined | |
| Core binding factor with KIT mutation | ||
| Poor/adverse | t(6;9)(p23;q34.1); DEK-NUP214 | Complex (≥3 clonal chromosomal abnormalities) |
| t(v;11q23.3); KMT2A rearranged | Monosomal karyotype | |
| t(9;22)(q34.1;q11.2); BCR-ABL1 | −5, 5q–, –7, 7q– | |
| inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2,MECOM(EVI1) | 11q23 – non t(9;11) | |
| −5 or del(5q); –7; –17/abn(17p) | inv(3), t(3;3) | |
| Complex karyotype,¶ monosomal karyotype# | t(6;9) | |
| Wild-type NPM1 and FLT3-ITDhigh | t(9;22) | |
| Mutated RUNX1** | Normal cytogenetics: with FLT3-ITD mutation†† | |
| Mutated ASXL1** | TP53 mutation | |
| Mutated TP53‡‡ |
| Risk category* . | ELN criteria10 . | NCCN criteria6 . |
|---|---|---|
| Favorable | t(8;21)(q22;q22.1); RUNX1-RUNX1T1 | Core binding factor: inv(16)†,‡ or t(16;16)†,‡ or t(8;21)†,‡ or t(15;17)‡ |
| inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11 | Normal cytogenetics: NPM1 mutation in absence of FLT3-ITD or isolated biallelic (double) CEBPA mutation | |
| Mutated NPM1 without FLT3-ITD or with FLT3-ITDlow§ | ||
| Biallelic mutated CEBPA | ||
| Intermediate | Mutated NPM1 and FLT3-ITDhigh§ | Normal cytogenetics |
| Wild-type NPM1 without FLT3-ITD or with FLT3-ITDlow§ (without adverse-risk genetic lesions) | +8 alone | |
| t(9;11)(p21.3;q23.3); MLLT3-KMT2A|| | t(9;11) | |
| Cytogenetic abnormalities not classified as favorable or adverse | Other nondefined | |
| Core binding factor with KIT mutation | ||
| Poor/adverse | t(6;9)(p23;q34.1); DEK-NUP214 | Complex (≥3 clonal chromosomal abnormalities) |
| t(v;11q23.3); KMT2A rearranged | Monosomal karyotype | |
| t(9;22)(q34.1;q11.2); BCR-ABL1 | −5, 5q–, –7, 7q– | |
| inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2,MECOM(EVI1) | 11q23 – non t(9;11) | |
| −5 or del(5q); –7; –17/abn(17p) | inv(3), t(3;3) | |
| Complex karyotype,¶ monosomal karyotype# | t(6;9) | |
| Wild-type NPM1 and FLT3-ITDhigh | t(9;22) | |
| Mutated RUNX1** | Normal cytogenetics: with FLT3-ITD mutation†† | |
| Mutated ASXL1** | TP53 mutation | |
| Mutated TP53‡‡ |
The prognostic value of a marker is treatment-dependent and may change with new therapies.
Presence of KIT mutations in patients with t(8:21) and, to a lesser extent, inv(16), confers a high risk of relapse; these patients should be considered intermediate risk and considered for HSCT if available.
Other cytogenetic findings in addition to these do not alter risk status.
Low, low allelic ratio (<0.5); high, high allelic ratio (≥0.5); recent studies indicate that AML with NPM1 mutation and FLT3-ITD low allelic ratio may also have a more favorable prognosis and patients should not routinely be assigned to allogeneic HCT.75,76
Presence of t(9;11)(p21.3;q23.3) takes precedence over rare, concurrent adverse-risk gene mutations.
3 or more chromosomal abnormalities in the absence of 1 of the World Health Organization–designated recurring translocations or inversions: t(8;21), inv(16) or t(16;16), t(9;11), t(v;11)(v;q23.3), t(6;9), inv(3) or t(3;3); AML with BCR-ABL1.
Defined by the presence of 1 single monosomy (excluding loss of X or Y) with at least 1 additional monosomy or structural chromosome abnormality (excluding core-binding factor AML).
These should not be used as adverse prognostic markers if they occur with favorable-risk AML subtypes.
FLT3-ITD mutations are considered to confer a significantly poorer outcome in patients with normal karyotype; there is controversy about whether FLT3-TKD mutations carry equally poor prognosis.
TP53 mutations are significantly associated with AML with complex and monosomal karyotype.
NCCN, National Comprehensive Cancer Network.