Myeloablative Conditioning (MAC)
Definition
- A high-dose chemotherapy (± total body irradiation, TBI) regimen that causes irreversible pancytopenia and marrow ablation.
- Requires stem cell rescue (autologous or allogeneic transplantation).
- Goal:
- Eradicate malignant cells (anti-tumor effect)
- Suppress host immunity to prevent graft rejection (in allogeneic SCT).
Common Myeloablative Regimens
- BEAM (BCNU, Etoposide, Ara-C, Melphalan) – common in lymphoma (autologous SCT)
- High-dose Melphalan (MEL200) – standard in multiple myeloma (autologous SCT)
- BuCy (Busulfan + Cyclophosphamide) – common in allogeneic SCT
- Cy/TBI (Cyclophosphamide + Total Body Irradiation) – another allo-SCT standard
- CBV (Cyclophosphamide, BCNU, Etoposide) – lymphoma
- TBI-based regimens – often used in pediatric ALL
Distinction from Other Conditioning Intensities
| Conditioning Type | Intensity | Effect on Marrow | Indications |
|---|---|---|---|
| Myeloablative (MAC) | High-dose | Complete & irreversible marrow ablation → requires stem cell rescue | Younger, fit patients; lymphoma, myeloma, ALL, AML |
| Reduced-Intensity Conditioning (RIC) | Intermediate | Some cytopenias but partial marrow recovery possible | Older or comorbid patients; relies on graft-versus-tumor effect in allo-SCT |
| Non-Myeloablative (“mini”) | Low-dose | Minimal cytopenias, not myeloablative | Frail/elderly allo-SCT patients, immunosuppression-based |
Toxicities & Pharmacist Considerations
- Mucositis → especially with melphalan, busulfan
- Organ toxicities:
- Pulmonary (carmustine)
- Hepatic veno-occlusive disease (busulfan, cyclophosphamide)
- Cardiotoxicity (cyclophosphamide, anthracyclines if used earlier)
- Neurotoxicity: Busulfan (seizures) → requires prophylaxis with levetiracetam or benzodiazepines
- Infections: Profound, prolonged neutropenia → broad antimicrobial prophylaxis
- Fertility: High risk of infertility → counseling prior to therapy
Pharmacist Role in MAC
- Dosing & PK monitoring (esp. busulfan → therapeutic drug monitoring to avoid underexposure or toxicity)
- Supportive care: growth factors, transfusions, cryotherapy, prophylaxis
- Organ monitoring: liver, lungs, heart, kidneys during and after conditioning
- Patient education: side effects, fertility, supportive medications
- Drug interactions: azole antifungals ↑ busulfan levels; allopurinol with cyclophosphamide