Treatment Approach for Acute Myeloid Leukemia
For patients with newly diagnosed AML, treatment selection must be based on age, performance status, cardiac function, cytogenetic/molecular risk profile, and FLT3 mutation status, with younger fit patients (<60-65 years) receiving intensive induction chemotherapy (cytarabine plus anthracycline), while older patients (≥60-65 years) or those with significant comorbidities including heart disease should receive non-intensive therapy with hypomethylating agents or venetoclax combinations rather than intensive chemotherapy. 1, 2, 3
Initial Risk Stratification and Diagnostic Workup
Before initiating any treatment, complete the following mandatory assessments:
Molecular and Cytogenetic Testing
- Obtain bone marrow aspirate for morphology, cytochemistry, immunophenotyping, conventional karyotyping, and molecular testing (FLT3-ITD, NPM1, CEBPA mutations) before starting chemotherapy. 1, 4
- FLT3 mutation testing is mandatory as it determines eligibility for midostaurin, which significantly improves outcomes when added to standard chemotherapy. 5
- HLA typing of patient and family members should be performed immediately at diagnosis for potential allogeneic stem cell transplantation candidates. 1
Cardiac Assessment for Patients with Heart Disease
- Perform cardiac echocardiography and assess cardiac risk factors at diagnosis, particularly before anthracycline-based therapy. 1
- Pre-existing coronary heart disease is a major risk factor for treatment complications and must be factored into the intensity of therapy selected. 1
- Anthracyclines carry cardiotoxicity risk, making cardiac evaluation essential before intensive chemotherapy. 1
Additional Pre-Treatment Evaluation
- Coagulation screening must be obtained before central line insertion, particularly to detect acute promyelocytic leukemia-related coagulopathy. 1
- CT chest and abdomen (or chest X-ray and abdominal ultrasound) to identify infectious foci and assess for extramedullary disease. 1
- Dental survey to identify root granulomas and caries that could become infectious foci during neutropenia. 1
Treatment Algorithm Based on Age and Fitness
Younger Patients (<60-65 Years) Without Significant Comorbidities
Intensive induction chemotherapy is the standard approach:
- Administer cytarabine plus anthracycline ("3+7" regimen) as induction chemotherapy. 1
- For FLT3-positive AML, add midostaurin 50 mg orally twice daily with food on Days 8-21 of each induction and consolidation cycle. 5
- Complete remission rates of 60-80% are expected in this population. 2
Risk-adapted consolidation therapy:
- Favorable-risk disease (APL with t(15;17), CBF-AML with t(8;21) or inv(16), biallelic CEBPA mutation, NPM1 mutation without FLT3-ITD): Chemotherapy-based consolidation with high-dose cytarabine, NOT allogeneic transplant in first remission. 1, 2
- Intermediate or adverse-risk disease: Allogeneic stem cell transplantation from HLA-identical sibling or matched unrelated donor in first remission. 1
- Complex karyotype (>3 abnormalities), monosomal karyotype, therapy-related AML, or antecedent myelodysplastic syndrome confer adverse prognosis. 1, 2
Older Patients (≥60-65 Years) or Those with Significant Comorbidities
The presence of heart disease, poor performance status (≥2), or other significant comorbidities mandates non-intensive therapy:
- Avoid intensive chemotherapy in patients ≥75 years, particularly with adverse cytogenetics or complex karyotype. 3
- Administer hypomethylating agents (azacitidine or decitabine) or venetoclax-based combinations as first-line therapy. 3
- Complete remission rates are only 40-50% with 5-year survival below 20% in this population, even with treatment. 2
- Treatment-related mortality is substantially higher due to comorbidities and reduced organ function. 2
Critical point: Low-dose cytarabine shows no benefit in patients with adverse cytogenetics and should not be used despite advanced age. 3
Patients with Excessive Leukocytosis
- Emergency leukapheresis coordinated with chemotherapy initiation is required for patients with clinical signs of leukostasis. 1, 4
- These patients are at particular risk for tumor lysis syndrome and require appropriate monitoring and prophylaxis. 1
Special Considerations for Acute Promyelocytic Leukemia (APL)
- APL with t(15;17) requires all-trans retinoic acid (ATRA) in addition to anthracycline-based induction. 1
- Maintenance chemotherapy and ATRA are beneficial in APL. 1
- For relapsed APL refractory to ATRA, arsenic trioxide can induce remission. 1
Treatment Setting and Supportive Care
- Treatment should only be administered in experienced centers with adequate multidisciplinary infrastructure, high case load, infectious disease support, and transfusion services. 1
- Central intravenous line insertion is required for all patients undergoing intensive chemotherapy, performed under platelet transfusion if necessary. 1
- Monitor patients receiving non-intensive therapy at least weekly for the first 4 weeks, every other week for the next 8 weeks, and monthly thereafter. 5
Critical Pitfalls to Avoid
Do not start chemotherapy before obtaining adequate diagnostic material for cytogenetic and molecular testing. The difference between favorable-risk and adverse-risk disease is dramatic, with 5-year survival ranging from >60% to <10% respectively. 2, 4
Do not withhold all antileukemic treatment based solely on age. Untreated AML has a median survival of less than 3 months, while non-intensive chemotherapy provides median survival of 5-14.4 months even in older patients. 6, 7, 8
Do not use intensive chemotherapy in patients ≥75 years with adverse cytogenetics, complex karyotype, or significant cardiac comorbidities. This approach offers minimal survival benefit with prohibitive early mortality risk. 3
Do not delay treatment for several days in patients with hyperleukocytosis and clinical leukostasis. Emergency intervention is required to prevent early mortality. 1, 4