What is the prognosis for a patient with Acute Myeloid Leukemia (AML)?

Prognosis of Acute Myeloid Leukemia

The prognosis of AML varies dramatically based on age, cytogenetics, molecular mutations, and disease characteristics, with 5-year overall survival ranging from less than 10% in older unfit patients to over 80% in favorable subtypes like acute promyelocytic leukemia (APL). 1, 2

Age-Stratified Prognosis

Younger Patients (≤60 years)

• Patients under 60 years receiving intensive chemotherapy have significantly better outcomes than older patients, with the "3+7" regimen producing estimated 5-year survival rates of approximately 35% in real-world experience 3
• Core-binding factor AML (CBF-AML) treated with fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin achieves estimated 10-year survival rates of ≥75% 3
• The median age at diagnosis is 68 years in the United States, indicating most patients fall into the older, higher-risk category 2

Older Patients (>60 years)

• Elderly patients have 5-year overall survival rates of less than 10%, particularly when unfit for intensive chemotherapy 4, 2
• Approximately 50% of older AML patients do not achieve complete remission after at least two courses of intensive induction therapy 1
• First-line treatment with low-dose cytarabine (LDAC) alone results in median overall survival of approximately 5 months 1
• Hypomethylating agents (HMAs) with venetoclax have become the new standard of care for older/unfit patients, improving survival over monotherapy 3

Molecular and Cytogenetic Risk Stratification

Favorable-Risk Disease

• APL with t(15;17) treated with all-trans retinoic acid (ATRA) and arsenic trioxide achieves estimated 10-year survival rates of ≥80% 3
• AML with t(8;21) and inv(16) are considered favorable prognostic factors 1
• NPM1-mutated AML without FLT3-ITD has favorable prognosis 5

Adverse-Risk Disease

• Complex aberrant karyotypes and TP53 mutations confer poor prognosis 1, 5
• Antecedent myelodysplastic syndrome or therapy-related AML (t-AML) are adverse prognostic factors 1
• FLT3-ITD mutations without NPM1 mutations indicate worse outcomes 5

Relapsed and Refractory Disease Prognosis

Primary Refractory AML

• Approximately 5% of children and 10-20% of younger adults have refractory disease after initial induction, with dismal prognosis and no realistic prospect of long-term survival after salvage chemotherapy alone 1
• Allogeneic hematopoietic stem cell transplantation (alloHCT) provides the most effective treatment option, offering long-term survival in 20-30% of primary refractory patients 1

Relapsed AML

• Approximately 30% of children and 50-70% of adults who achieve complete remission will experience relapse 1
• Early relapse (within 1 year of initial diagnosis) carries particularly poor prognosis 1
• The international Relapsed AML 2001/01 study showed second complete remission rates of 59-69% with fludarabine/cytarabine-based regimens, translating to overall survival of 38% for all relapsed patients 1
• Early treatment response (bone marrow evaluation before second reinduction) is the most important prognostic factor in relapsed AML 1
• Duration of first complete remission and core-binding factor leukemia status are also important prognostic factors at relapse 1

Post-Transplant Relapse

• Patients relapsing after alloHCT have survival probabilities at 3 years of 4%, 12%, 26%, and 38% for those relapsing within 6 months, 6-24 months, 2-3 years, or >3 years after transplant, respectively 1
• Second alloHCT or donor lymphocyte infusion may induce long-term survival in patients relapsing later than 5 months after first transplant 1

Special Prognostic Considerations

Acute Promyelocytic Leukemia

• APL is considered a medical emergency due to risk of life-threatening hemorrhage, but has excellent prognosis when treated appropriately 1
• Pseudotumor cerebri occurs in 11% of children during initial ATRA administration 1
• APL differentiation syndrome occurs in 10% of children treated with ATRA or arsenic trioxide 1

Therapy-Related AML

• Therapy-related secondary AML (t-AML) is one of the most frequent secondary malignancies and generally has poor prognosis 1

Critical Prognostic Pitfalls

• Patients with poor performance status and considerable comorbidity have significantly worse outcomes and may not benefit from curative-intent therapy 1
• Patients who respond poorly to first reinduction, do not achieve second complete remission, or relapse for the second time have extremely poor prognosis and should be offered experimental therapy or palliation 1
• Survival rates with alloHCT in AML with blast persistence are generally poor 1
• The prognosis of primary refractory and relapsed AML patients remains poor despite advances in therapy 1