What is the prognosis for Acute Myeloid Leukemia (AML) patients?

AML Prognosis

The prognosis of AML is highly heterogeneous and primarily determined by cytogenetic abnormalities (the strongest prognostic factor), molecular mutations, patient age, and treatment response, with overall 5-year survival ranging from >70% in favorable-risk pediatric patients to <23% in adverse-risk adults. 1

Risk Stratification Framework

Cytogenetic Risk Groups (Strongest Prognostic Factor)

Cytogenetics represent the most powerful predictor of response to induction therapy and survival. 1

Favorable Risk (5-year survival >60% adults, >70% children):

• t(8;21)(q22;q22)/RUNX1-RUNX1T1 1
• inv(16)(p13.1q22)/CBFB-MYH11 1
• t(15;17)(q22;q21)/PML-RARA 1
• Biallelic CEBPA mutations 1
• NPM1 mutation without FLT3-ITD 1

Intermediate Risk (5-year survival 23-60% adults, 50-70% children):

• Cytogenetically normal AML without favorable molecular markers 1
• t(9;11)(p22;q23)/MLLT3-MLL 1

Adverse Risk (5-year survival <23% adults, <50% children):

• Complex karyotype (≥3 chromosomal abnormalities, occurring in 10-12% of patients) 1
• Monosomy 5, deletion 5q 1
• Monosomy 7 1
• inv(3)(q21q26.2) or t(3;3)(q21;q26.2)/RPN1-EVI1 (3-year OS 8.8% in newly diagnosed patients) 1, 2
• t(6;9)(p23;q34)/DEK-NUP214 1
• t(6;11)(q27;q23)/MLL-MLLT4(AF6) 1
• t(10;11)(p12;q23)/MLL-MLLT10(AF10) 1
• t(7;12)(q36;p13) (pediatric-specific) 1
• t(5;11)(q35;p15.5)/NUP98-NSD1 (pediatric-specific) 1

Molecular Genetic Refinement

Within cytogenetically normal AML, molecular mutations critically refine prognosis: 1, 3

Favorable molecular markers:

• NPM1 mutation without FLT3-ITD (survival comparable to CBF-AML) 1
• Biallelic CEBPA mutations (only double mutations confer favorable prognosis, not single mutations) 1

Adverse molecular markers:

• FLT3-ITD, particularly with high mutant allele burden 1, 3
• KIT mutations in CBF-AML (unfavorable impact on otherwise favorable cytogenetics) 1
• WT1, RUNX1, ASXL1, DNMT3A mutations 1, 2

A critical caveat: The favorable impact of NPM1 mutation is completely negated by concurrent FLT3-ITD, emphasizing the importance of combined molecular profiling rather than single-marker assessment. 1

Patient-Related Prognostic Factors

Age is the single most important patient-related adverse prognostic factor, independent of disease biology: 1, 4

• Younger adults (18-60 years): 30-40% 5-year survival 1
• Older adults (>60 years): Significantly worse outcomes due to higher frequency of adverse cytogenetics, increased treatment-related mortality, and inability to tolerate intensive therapy 1
• Pediatric patients (<18 years): 60-75% 5-year survival 1

Secondary AML (following MDS or prior cytotoxic therapy) carries uniformly poor prognosis: 1

• Therapy-related AML (t-AML) remains an independent adverse prognostic factor even after adjusting for cytogenetics 1
• Overall survival with t-AML approximately 20-30% with allogeneic HSCT 1

Other patient factors affecting prognosis:

• Performance status 3, 5
• White blood cell count ≥20×10⁹/L (associated with increased early death risk) 1, 5, 2

Treatment Response as Prognostic Indicator

Treatment response assessment after induction therapy is recommended for risk stratification: 1

• Complete remission (CR) rates vary by risk group and treatment intensity 6
• Minimal residual disease (MRD) monitoring provides independent prognostic information, particularly in favorable-risk subgroups 1
• For CBF-AML, transcript levels below 10-12 copies (normalized to 10⁴ ABL1 copies) predict long-term remission 1

Relapsed/Refractory Disease Prognosis

Relapsed AML carries extremely poor prognosis, stratified by a validated prognostic index: 1

• Favorable relapse risk (9% of patients): 1-year survival 70%, 5-year survival 46% 1
• Intermediate relapse risk (25% of patients): 1-year survival 49%, 5-year survival 18% 1
• Unfavorable relapse risk (66% of patients): 1-year survival 16%, 5-year survival 4% 1

Key relapse risk factors include: duration of first remission (<6 months worst), cytogenetics at diagnosis, prior HSCT, and age at relapse. 1

Critical Clinical Pitfalls

Do not rely on single prognostic markers in isolation - the interaction between cytogenetics and molecular mutations fundamentally alters prognosis (e.g., KIT mutations worsen otherwise favorable CBF-AML, while FLT3-ITD negates favorable NPM1 mutations). 1, 3

Complex karyotype with TP53 mutations (occurring in approximately two-thirds of complex karyotype cases) represents one of the most adverse prognostic subgroups with very poor outcomes. 1

The 30-day mortality with intensive induction chemotherapy can reach 14% in certain high-risk populations, necessitating careful patient selection for intensive versus low-intensity approaches. 2