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

AML Prognosis

The prognosis of AML is highly heterogeneous, ranging from >70% 5-year survival in favorable-risk pediatric patients to <23% in adverse-risk adults, with cytogenetic abnormalities serving as the most powerful predictor of outcomes. 1

Risk Stratification by Cytogenetics

The cytogenetic profile at diagnosis is the single strongest disease-specific prognostic factor and should be obtained immediately to guide treatment decisions 1, 2:

Favorable-risk cytogenetics (best prognosis):

• t(8;21)(q22;q22)/RUNX1-RUNX1T1 1
• inv(16)(p13.1q22)/CBFB-MYH11 1
• t(15;17)(q22;q21)/PML-RARA (acute promyelocytic leukemia) 1

Intermediate-risk cytogenetics (moderate prognosis):

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

Adverse-risk cytogenetics (worst prognosis):

• Complex karyotype 1
• Monosomy 5, deletion 5q, or monosomy 7 1, 3
• inv(3)(q21q26.2) or t(3;3)(q21;q26.2)/RPN1-EVI1 with 3-year overall survival of only 8.8% 1, 4
• t(6;9)(p23;q34)/DEK-NUP214 1

Molecular Refinement in Cytogenetically Normal AML

For patients with normal cytogenetics (intermediate-risk), molecular mutations critically refine prognosis 1, 5:

Favorable molecular markers:

• NPM1 mutation without FLT3-ITD 1, 2
• Biallelic CEBPA mutations 1, 5

Adverse molecular markers:

• FLT3-ITD, particularly with high mutant allele burden 1, 2
• KIT mutations in core-binding factor AML 1
• WT1, RUNX1, ASXL1, DNMT3A mutations 1

Patient-Related Prognostic Factors

Age is the single most important patient-related adverse prognostic factor, independent of disease biology 1, 2, 6:

• Pediatric patients (<18 years): 60-75% 5-year survival 1
• Younger adults (18-60 years): 30-40% 5-year survival 1
• Older adults (>60 years): Significantly worse outcomes, often <10% 5-year survival 1, 3

Secondary AML carries uniformly poor prognosis:

• AML following myelodysplastic syndrome (MDS) 1, 2
• Therapy-related AML (t-AML) following prior cytotoxic therapy remains an independent adverse prognostic factor even after adjusting for cytogenetics 1, 3

Treatment Response as Prognostic Indicator

Complete remission (CR) rates vary substantially by risk group:

• CR rates range from 46% overall in newly diagnosed patients with adverse cytogenetics like inv(3)/t(3;3) 4
• Minimal residual disease (MRD) monitoring provides independent prognostic information and is increasingly important for risk stratification, particularly in favorable-risk subgroups 1

Relapsed/Refractory Disease Prognosis

Relapsed AML carries extremely poor prognosis with 3-year overall survival of only 7.1% 4:

Key relapse risk factors:

• Duration of first remission (<6 months is worst) 1
• Cytogenetics at diagnosis 1
• Prior hematopoietic stem cell transplantation 1
• Age at relapse 1

Favorable relapse risk patients: 1-year survival 70%, 5-year survival 46% 1

Critical Pitfall

The most common pitfall is failing to obtain comprehensive cytogenetic and molecular testing at diagnosis, as this information is essential for accurate prognostication and treatment planning. Additionally, age alone should not exclude patients from intensive therapy consideration, as molecular and cytogenetic features may override age-related risk in select cases 1, 2.