2022 ELN risk classification by genetics at initial diagnosis*
| Risk category† . | Genetic abnormality . |
|---|---|
| Favorable | • t(8;21)(q22;q22.1)/RUNX1::RUNX1T1†,‡ • inv(16)(p13.1q22) or t(16;16)(p13.1;q22)/ CBFB::MYH11†,‡ • Mutated NPM1†,§ without FLT3-ITD • bZIP in-frame mutated CEBPA∥ |
| Intermediate | • Mutated NPM1†,§ with FLT3-ITD • Wild-type NPM1 with FLT3-ITD (without adverse-risk genetic lesions) • t(9;11)(p21.3;q23.3)/MLLT3::KMT2A†,¶ • Cytogenetic and/or molecular abnormalities not classified as favorable or adverse |
| Adverse | • t(6;9)(p23.3;q34.1)/DEK::NUP214 • t(v;11q23.3)/KMT2A-rearranged# • t(9;22)(q34.1;q11.2)/BCR::ABL1 • t(8;16)(p11.2;p13.3)/KAT6A::CREBBP • inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/ GATA2, MECOM(EVI1) • t(3q26.2;v)/MECOM(EVI1)-rearranged • −5 or del(5q); −7; −17/abn(17p) • Complex karyotype,** monosomal karyotype†† • Mutated ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2‡‡ • Mutated TP53a |
| Risk category† . | Genetic abnormality . |
|---|---|
| Favorable | • t(8;21)(q22;q22.1)/RUNX1::RUNX1T1†,‡ • inv(16)(p13.1q22) or t(16;16)(p13.1;q22)/ CBFB::MYH11†,‡ • Mutated NPM1†,§ without FLT3-ITD • bZIP in-frame mutated CEBPA∥ |
| Intermediate | • Mutated NPM1†,§ with FLT3-ITD • Wild-type NPM1 with FLT3-ITD (without adverse-risk genetic lesions) • t(9;11)(p21.3;q23.3)/MLLT3::KMT2A†,¶ • Cytogenetic and/or molecular abnormalities not classified as favorable or adverse |
| Adverse | • t(6;9)(p23.3;q34.1)/DEK::NUP214 • t(v;11q23.3)/KMT2A-rearranged# • t(9;22)(q34.1;q11.2)/BCR::ABL1 • t(8;16)(p11.2;p13.3)/KAT6A::CREBBP • inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/ GATA2, MECOM(EVI1) • t(3q26.2;v)/MECOM(EVI1)-rearranged • −5 or del(5q); −7; −17/abn(17p) • Complex karyotype,** monosomal karyotype†† • Mutated ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2‡‡ • Mutated TP53a |
Frequencies, response rates and outcome measures should be reported by risk category, and, if sufficient numbers are available, by specific genetic lesions indicated.
Mainly based on results observed in intensively treated patients. Initial risk assignment may change during the treatment course based on the results from analyses of measurable residual disease.
Concurrent KIT and/or FLT3 gene mutation does not alter risk categorization.
AML with NPM1 mutation and adverse-risk cytogenetic abnormalities are categorized as adverse-risk.
Only in-frame mutations affecting the basic leucine zipper (bZIP) region of CEBPA, irrespective whether they occur as monoallelic or biallelic mutations, have been associated with favorable outcome.
The presence of t(9;11)(p21.3;q23.3) takes precedence over rare, concurrent adverse-risk gene mutations.
Excluding KMT2A partial tandem duplication (PTD).
Complex karyotype: ≥3 unrelated chromosome abnormalities in the absence of other class-defining recurring genetic abnormalities; excludes hyperdiploid karyotypes with three or more trisomies (or polysomies) without structural abnormalities.
Monosomal karyotype: presence of two or more distinct monosomies (excluding loss of X or Y), or one single autosomal monosomy in combination with at least one structural chromosome abnormality (excluding core-binding factor AML).
For the time being, these markers should not be used as an adverse prognostic marker if they co-occur with favorable-risk AML subtypes.
TP53 mutation at a variant allele fraction of at least 10%, irrespective of the TP53 allelic status (mono- or biallelic mutation); TP53 mutations are significantly associated with AML with complex and monosomal karyotype.