Acute myeloid leukemia

European LeukemiaNet: risk stratification by genetic abnormality at initial diagnosis[23]Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022 Sep 22;140(12):1345-77. https://www.doi.org/10.1182/blood.2022016867 http://www.ncbi.nlm.nih.gov/pubmed/35797463?tool=bestpractice.com

Favorable risk

• 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**

• Basic leucine zipper (bZIP) in-frame mutated CEBPA

Intermediate risk

• 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 risk

• t(6;9)(p23.3;q34.1)/DEK::NUP214

• t(v;11q23.3)/KMT2A-rearranged (excluding KMT2A partial tandem duplication)

• 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 (≥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 ≥2 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])

• Mutated ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2 (these mutations should not be used as adverse prognostic markers if they co-occur with favorable-risk AML subtypes)

• Mutated TP53 (variant allele fraction ≥10%)

*KIT and/or FLT3 mutation does not alter risk categorization

**AML with NPM1 mutation and adverse-risk cytogenetic abnormalities are categorized as adverse risk.

European LeukemiaNet: treatment response criteria[23]Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022 Sep 22;140(12):1345-77. https://www.doi.org/10.1182/blood.2022016867 http://www.ncbi.nlm.nih.gov/pubmed/35797463?tool=bestpractice.com

Complete remission (CR)

• Bone marrow blasts <5%; absence of circulating blasts; absence of extramedullary disease

• Absolute neutrophil count (ANC) ≥1000/microliter (≥1 × 10⁹/L)

• Platelet count ≥100,000/microliter (≥100 × 10⁹/L)

CR with partial hematologic recovery (CRh)

• Bone marrow blasts <5%; absence of circulating blasts; absence of extramedullary disease

• ANC ≥500/microliter (≥0.5 × 10⁹/L)

• Platelet count ≥50,000/microliter (≥50 × 10⁹/L)

CR with incomplete hematologic recovery (CRi)

• All CR criteria except for residual neutropenia (ANC <1000/microliter [<1 × 10⁹/L]) or thrombocytopenia (platelet count <100,000/microliter [<100 × 10⁹/L])

Morphologic leukemia-free state (MLFS)

• Bone marrow blasts <5%; absence of circulating blasts; absence of extramedullary disease; no hematologic recovery required

• Note: bone marrow should not merely be "aplastic"; bone marrow spicules should be present; ≥200 cells should be enumerated in the aspirate or cellularity should be ≥10% in the biopsy

Partial remission (PR)

• All hematologic criteria of CR

• Decrease of bone marrow blast percentage to 5% to 25%

• Decrease of pretreatment bone marrow blast percentage by ≥50%

No response

• Patients evaluable for response but not meeting the criteria for CR, CRh, CRi, MLFS, or PR are categorized as having no response prior to the response landmark. Patients failing to achieve response by the designated landmark are designated as having refractory disease.

Nonevaluable for response

• Includes patients lacking an adequate bone marrow response evaluation (includes those with early death, withdrawal prior to response assessment, or a technically suboptimal bone marrow sample precluding assessment).

CR, CRh, or CRi without measurable (minimal) residual disease (MRD) (CRMRD-, CRhMRD-, or CRiMRD-)

• CR, CRh, or CRi with MRD below a defined threshold for a genetic marker by quantitative polymerase chain reaction (qPCR) or multiparameter flow cytometry.

• Response without MRD should be confirmed with a subsequent assessment at least 4 weeks apart. The date of response without MRD is the first date in which the MRD was below the defined threshold.

• Response with MRD detection at low-level (CRMRD-LL) is included in this category of CR, CRh, or CRi without MRD. CRMRD-LL is currently only defined for NPM1-mutant and core-binding factor AML.

Refractory disease

• No CR, CRh, or CRi at the response landmark.

Relapsed disease (after CR, CRh, or CRi)

• Bone marrow blasts ≥5%; or reappearance of blasts in the blood in at least 2 peripheral blood samples at least one week apart; or development of extramedullary disease.

MRD relapse (after CR, CRh, or CRi without MRD)

• 1) conversion from MRD negativity to MRD positivity, independent of method; or 2) increase of MRD copy numbers ≥1 log10 between any two positive samples in patients with CRMRD-LL, CRhMRD-LL, or CRiMRD-LL by qPCR.

• The result of 1 or 2 should be rapidly confirmed in a second consecutive sample from the same tissue source.