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

Acute Myeloid Leukemia Prognosis

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

Cytogenetic Risk Stratification

Cytogenetics represent the single most powerful predictor of treatment response and survival in AML. 2, 1

Favorable-Risk Cytogenetics

• t(8;21)(q22;q22)/RUNX1-RUNX1T1, inv(16)(p13.1q22)/CBFB-MYH11, and t(15;17)(q22;q21)/PML-RARA define the favorable-risk category 2, 1
• Acute promyelocytic leukemia (APL) with t(15;17) has distinct biology with >80% cure rates using ATRA-based regimens 3

Intermediate-Risk Cytogenetics

• Cytogenetically normal AML without favorable molecular markers comprises the intermediate-risk group 2, 1
• t(9;11)(p22;q23)/MLLT3-MLL also falls into intermediate risk 2, 1

Adverse-Risk Cytogenetics

• Complex karyotype (≥3 chromosome abnormalities), monosomy 5, deletion 5q, monosomy 7, inv(3)(q21q26.2) or t(3;3)(q21;q26.2)/RPN1-EVI1, and t(6;9)(p23;q34)/DEK-NUP214 define adverse-risk disease 2, 1
• Complex karyotype occurs in 10-12% of patients and carries very poor outcomes 2
• AML with inv(3)/t(3;3) has particularly dismal prognosis with 3-year overall survival of only 8.8% in newly diagnosed patients and 81.7% cumulative incidence of relapse 4

Molecular Genetic Refinement

Within cytogenetically normal AML, molecular mutations critically refine prognosis and guide treatment decisions. 1

Favorable Molecular Markers

• NPM1 mutation without FLT3-ITD confers favorable prognosis 2, 1
• Biallelic CEBPA mutations are associated with improved outcomes 2, 1

Adverse Molecular Markers

• FLT3-ITD, particularly with high mutant allele burden, predicts poor outcomes 2, 1
• KIT mutations in core-binding factor AML worsen otherwise favorable prognosis 1
• WT1, RUNX1, ASXL1, and DNMT3A mutations are adverse prognostic factors 1
• FLT3-mutated AML treated with midostaurin plus chemotherapy showed improved overall survival (HR 0.77; 95% CI 0.63-0.95; p=0.016) compared to chemotherapy alone 5

Patient-Related Prognostic Factors

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

Age-Stratified Survival

• 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 with increased treatment-related mortality 2, 1
• The median age at AML diagnosis is 67 years for non-APL subtypes 3

Secondary AML

• Secondary AML (following MDS or prior cytotoxic therapy) carries uniformly poor prognosis 2, 1
• Therapy-related AML (t-AML) remains an independent adverse prognostic factor even after adjusting for cytogenetics 1

Other Patient Factors

• Performance status significantly impacts treatment-related mortality, particularly in older patients 2
• Presenting WBC count influences prognosis, with elevated counts associated with worse outcomes 2

Treatment Response and Minimal Residual Disease

Achievement of complete remission and depth of response are critical prognostic indicators. 1

• Complete remission (CR) rates vary by risk group and treatment intensity, with favorable-risk disease achieving >90% CR rates 3
• Minimal residual disease (MRD) monitoring provides independent prognostic information, particularly in favorable-risk subgroups 1
• Event-free survival is significantly improved with targeted therapy in FLT3-mutated AML (median 8.2 vs 3.0 months, HR 0.78; p=0.005) 5

Relapsed/Refractory Disease

Relapsed AML carries extremely poor prognosis with outcomes stratified by duration of first remission, cytogenetics, prior transplant, and age. 1

• Favorable relapse risk: 1-year survival 70%, 5-year survival 46% 1
• Duration of first remission <6 months confers the worst prognosis 1
• In relapsed/refractory patients with inv(3)/t(3;3), the composite CR rate is only 14% overall, though venetoclax-based regimens achieved 33% CR rates 4

Role of Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation in first complete remission dramatically improves outcomes in appropriate risk groups. 1, 4

• 5-year overall survival: 44% with transplant vs 6% without transplant in first CR for high-risk disease 4
• Approximately 59% of patients with FLT3-mutated AML undergo transplantation during their disease course 5