A 45-year-old man with newly diagnosed acute myeloid leukemia (AML) without favorable cytogenetics and with normal renal and cardiac function is being considered for induction therapy. What is the drug of choice for standard-risk AML induction in this patient?

Question

Accepted Answer

B. Daunorubicin + cytarabine (7+3 regimen). ## Standard-Risk AML Induction: Anthracycline-Based Chemotherapy

**Key Point:** The "7+3" regimen (daunorubicin + cytarabine) remains the gold standard induction for fit, newly diagnosed AML patients without favorable cytogenetics.

### Regimen Components and Mechanism

| Drug | Dose | Duration | Mechanism |
|------|------|----------|----------|
| **Daunorubicin** | 60–90 mg/m² IV | Days 1–3 | Topoisomerase II inhibitor; intercalates DNA |
| **Cytarabine** | 100–200 mg/m² IV continuous | Days 1–7 | Nucleoside analog; S-phase specific |

### Historical Context & Evidence
- The 7+3 regimen has been the standard since the 1970s and remains the benchmark against which all new regimens are compared.
- Achieves **60–80% complete remission (CR)** in younger, fit patients with standard-risk AML.
- **High-Yield:** Intensification with high-dose daunorubicin (90 mg/m²) or idarubicin improves CR rates and overall survival compared to standard-dose daunorubicin (45 mg/m²).

### Patient Selection for 7+3
- **Age:** <60 years (or fit ≥60 years).
- **Performance status:** ECOG 0–2.
- **Organ function:** Normal renal and cardiac function (as in this case).
- **Cytogenetics:** Standard-risk (no t(15;17), t(8;21), inv(16)).

### Clinical Pearl
- **Tumor lysis syndrome (TLS) risk:** AML has lower TLS risk than ALL, but prophylaxis (allopurinol/rasburicase, hydration) is still recommended, especially in high WBC counts.
- **Consolidation:** Post-remission therapy is critical — typically 3–4 cycles of high-dose cytarabine (HiDAC) in younger patients or allogeneic hematopoietic stem cell transplantation (HSCT) in first remission for high-risk disease.

### Why NOT Hypomethylating Agents or Venetoclax in Fit Patients?

| Regimen | Best Use | Why Not Standard-Risk Fit? |
|---------|----------|---------------------------|
| Azacitidine/Decitabine monotherapy | Unfit, elderly (≥75 yr), comorbidities | Lower CR rates (~30–40%); reserved for patients who cannot tolerate intensive chemotherapy |
| Venetoclax + azacitidine | Unfit/elderly AML | Emerging option but not yet standard for fit patients; data still maturing |
| 7+3 | **Fit, standard-risk AML** | **Superior CR and OS; proven long-term benefit** |

**Mnemonic:** **FIT = 7+3** (Fit patients get intensive chemotherapy; Infirm/elderly get hypomethylating agents or venetoclax combinations).

[cite:Harrison 21e Ch 110]

Answer

A. Azacitidine monotherapy

Answer

C. Venetoclax + azacitidine

Answer

D. Decitabine monotherapy

A 45-year-old man with newly diagnosed acute myeloid leukemia (AML) without favorable cytogenetics and with normal renal and cardiac function is being considered for induction therapy. What is the drug of choice for standard-risk AML induction in this patient?

Explanation

Standard-Risk AML Induction: Anthracycline-Based Chemotherapy

Regimen Components and Mechanism

Historical Context & Evidence

Patient Selection for 7+3

Clinical Pearl

Why NOT Hypomethylating Agents or Venetoclax in Fit Patients?

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Drug	Dose	Duration	Mechanism
Daunorubicin	60–90 mg/m² IV	Days 1–3	Topoisomerase II inhibitor; intercalates DNA
Cytarabine	100–200 mg/m² IV continuous	Days 1–7	Nucleoside analog; S-phase specific

Regimen	Best Use	Why Not Standard-Risk Fit?
Azacitidine/Decitabine monotherapy	Unfit, elderly (≥75 yr), comorbidities	Lower CR rates (~30–40%); reserved for patients who cannot tolerate intensive chemotherapy
Venetoclax + azacitidine	Unfit/elderly AML	Emerging option but not yet standard for fit patients; data still maturing
7+3	Fit, standard-risk AML	Superior CR and OS; proven long-term benefit