What are the diagnostic criteria and treatment options for a 60-year-old adult with suspected acute myeloid leukemia (AML)?

Acute Myeloid Leukemia Diagnosis and Treatment in a 60-Year-Old Adult

Diagnose AML by obtaining bone marrow aspirate and peripheral blood samples with comprehensive workup including morphology, cytochemistry, immunophenotyping, conventional cytogenetics, and molecular testing for FLT3, NPM1, and CEBPA mutations, then treat fit patients with induction chemotherapy using an anthracycline plus cytarabine followed by risk-stratified consolidation therapy. 1, 2

Diagnostic Criteria

The diagnosis requires ≥20% blasts in bone marrow or peripheral blood, with bone marrow aspiration being mandatory for all suspected cases. 2

Essential Initial Workup

• Obtain comprehensive medical history documenting any prior growth factor therapy, transfusions, medications, family history of hematologic disorders, and comorbidities (particularly diabetes and coronary heart disease which affect intensive chemotherapy feasibility) 1, 3
• Perform complete blood count with differential and peripheral blood smear morphologic assessment 1
• Bone marrow aspirate is the cornerstone—count at least 500 nucleated cells on marrow smears containing spicules 2
• Obtain bone marrow core biopsy with trephine touch preparations evaluated in conjunction with aspirates 1

Required Laboratory Studies

• Conventional cytogenetic analysis (karyotype) is mandatory and cannot be replaced by molecular testing or FISH alone—this provides critical prognostic information as chromosomal abnormalities are detected in the majority of AML cases 2, 1
• Multiparameter flow cytometry (minimum 3-4 color) on bone marrow aspirate to distinguish AML from early T-ALL, B-ALL, and acute leukemia of ambiguous lineage 2, 1
• FLT3-ITD mutation testing is required for all patients with suspected or confirmed AML for prognostic stratification and targeted therapy decisions 1, 2
• For non-core binding factor (CBF) AML and non-APL cases, perform mutational analysis for NPM1, CEBPA, and RUNX1 1
• For CBF AML (with t(8;21) or inv(16)/t(16;16)), ensure KIT mutation analysis 1
• If morphology suggests acute promyelocytic leukemia (APL), perform rapid detection of PML-RARA 1

Additional Pre-Treatment Assessment

• Coagulation screening (PT, PTT, fibrinogen) before central line insertion and to detect leukemia-related coagulopathy, particularly if APL is suspected 3
• Echocardiography for patients with cardiac risk factors or history of heart disease, as anthracyclines are cardiotoxic 3
• HLA typing of patient and family members if allogeneic stem cell transplantation is being considered 3
• If infection suspected, obtain thoracic CT and abdominal ultrasound or CT to assess lungs, liver, spleen, lymph nodes, and kidneys 3
• If extramedullary disease suspected, perform PET/CT 1

Risk Stratification

At age 60, this patient faces adverse prognosis with increased susceptibility to treatment complications and higher frequency of unfavorable cytogenetics. 3, 2

Favorable Risk Features

• Chromosomal translocations: t(15;17) (APL), t(8;21), inv(16)/t(16;16) 3, 2
• NPM1 mutations (in absence of FLT3-ITD) 3
• Biallelic CEBPA mutations 3

Adverse Risk Features

• Complex aberrant karyotype 3, 2
• Antecedent or concomitant myelodysplastic syndrome 3, 2
• FLT3 gene alterations 3
• Age >60 years (this patient) 3, 2
• Preexisting medical conditions (diabetes, coronary heart disease) that affect intensive chemotherapy feasibility 3

Treatment Approach

Postpone chemotherapy until all satisfactory diagnostic material has been harvested. 3

For Fit Patients (Good Performance Status, Minimal Comorbidity)

Induction chemotherapy should include an anthracycline plus cytarabine (Ara-C). 3

• Standard induction: cytarabine 100 mg/m²/day by continuous IV infusion for Days 1-7, or 100 mg/m² IV every 12 hours for Days 1-7, combined with an anthracycline 4
• If excessive leukocytosis at presentation, emergency leukapheresis may be required before induction 3
• For APL specifically, add all-trans retinoic acid (ATRA) to anthracycline-based induction 3
• Patients failing to respond to 1-2 cycles are considered refractory 3

Consolidation Therapy (Risk-Stratified)

Patients achieving complete remission should receive post-remission therapy, with the approach determined by risk stratification. 3

• Favorable risk (t(15;17), t(8;21), inv(16), NPM1 mutation, CEBPA mutation): chemotherapy only, preferably with high-dose cytarabine 3
• Intermediate/poor risk with HLA-identical sibling: allogeneic stem cell transplantation in first remission 3
• Poor risk features without family donor: consider matched unrelated donor allogeneic transplant 3
• Identify candidates for allogeneic stem cell transplantation early during induction 3
• Maintenance chemotherapy and ATRA are beneficial in APL only 3

For Unfit Patients (Poor Performance Status, Significant Comorbidity)

Patients not eligible for curative intensive treatment should receive supportive care. 3

• Consider hypomethylating agents combined with venetoclax, which has revolutionized therapy in older adults and extends survival over monotherapy 5
• Molecularly targeted therapies based on genomic profile: midostaurin, gilteritinib, or quizartinib for FLT3 variants; ivosidenib or olutasidenib for IDH1 variants; enasidenib for IDH2 variants 5

Critical Pitfalls to Avoid

• Never start chemotherapy before obtaining adequate diagnostic material for morphology, cytogenetics, and molecular testing 3, 1
• Do not rely on molecular genetic or FISH testing alone—conventional karyotyping is mandatory 2
• Ensure the same physician interprets both bone marrow aspirate smears and core biopsy specimens, or correlate interpretations if performed by different physicians 2
• Monitor for cytarabine syndrome (fever, myalgia, bone pain, rash, conjunctivitis occurring 6-12 hours post-administration)—treat with corticosteroids if needed 4
• Watch for severe toxicities: myelosuppression with nadir at days 15-24 for white cells and days 12-15 for platelets 4
• Provide comprehensive supportive care including blood product transfusions, antimicrobial prophylaxis/treatment, and frequent monitoring for chemotherapy complications 6

Treatment Setting

AML treatment should be carried out in centers offering multidisciplinary approach with full hematology/oncology service, bone marrow transplant unit collaboration, infectious disease expertise, and adequate transfusion services. 3