Which feature best discriminates busulfan from melphalan among alkylating agents used in cancer chemotherapy?

Explanation

## Busulfan vs. Melphalan: Key Discriminating Features ### Clinical Use and Organ Toxicity **Key Point:** The most clinically important distinction is busulfan's **pulmonary fibrosis** toxicity and its role in myeloablative conditioning, versus melphalan's use in multiple myeloma without significant pulmonary risk. ### Comparative Table | Feature | Busulfan | Melphalan | |---------|----------|----------| | **Primary indication** | Chronic myeloid leukemia (CML), bone marrow conditioning | Multiple myeloma, lymphoma | | **Dose-limiting toxicity** | Pulmonary fibrosis (1–10% incidence) | Bone marrow suppression | | **Pulmonary risk** | HIGH — can be fatal | Minimal | | **Route of administration** | IV (preferred) or oral | Oral or IV | | **Mechanism of activation** | Requires glutathione conjugation | Direct alkylating agent | | **Use in transplantation** | Standard myeloablative agent | Occasional conditioning | ### Busulfan-Specific Toxicity: Pulmonary Fibrosis 1. **Incidence:** 1–10% of treated patients 2. **Onset:** Usually 4–6 months after therapy (can be delayed years) 3. **Mechanism:** Direct lung epithelial damage → inflammatory cascade → fibrosis 4. **Prevention:** Adequate hydration, monitoring for early symptoms 5. **Management:** Discontinue if suspected; corticosteroids may help early **Clinical Pearl:** Busulfan is the **preferred myeloablative agent** for bone marrow transplantation conditioning, especially in CML. However, pulmonary fibrosis is a serious late complication that must be monitored. ### Melphalan in Multiple Myeloma - Standard agent for myeloma induction (often with prednisone: MP regimen) - Bone marrow suppression is the dose-limiting toxicity, not pulmonary fibrosis - Well-tolerated with minimal organ-specific toxicities - Can be given orally or IV **High-Yield:** **Busulfan → Lungs** (pulmonary fibrosis); **Melphalan → Myeloma** (standard treatment). This mnemonic helps distinguish their clinical roles and toxicity profiles. **Mnemonic:** **BUSAL** → **BU**sulfan → **AL**veolar fibrosis (pulmonary) [cite:KD Tripathi 8e Ch 62; Harrison 21e Ch 104]