Bone Marrow Transplant Preparation
Prior to bone marrow (hematopoietic stem cell) transplant, patients receive a conditioning regimen consisting of chemotherapy, serotherapy, and/or radiation to eradicate malignant cells and induce immunosuppression for donor cell engraftment. 1
Conditioning Regimen Selection
The preparative regimen choice depends on four key factors:
- Disease type and stage (e.g., AML, ALL, MDS, lymphoma, multiple myeloma)
- Patient age and comorbidities
- Transplant type (autologous vs. allogeneic)
- Donor source (matched sibling, unrelated, haploidentical, cord blood)
Myeloablative Conditioning (MAC)
MAC regimens are used for younger patients (<55 years) with good organ function 2. These high-intensity regimens include:
- ≥100 mg/kg cyclophosphamide or 3.6 mg/m² IV
- ≥12 Gy total body irradiation (TBI)
- ≥16 mg/kg oral busulfan or 9.6 mg/kg IV busulfan 2
Traditional MAC combinations:
- TBI/Cyclophosphamide: 12-13.8 Gy TBI plus 120 mg/kg cyclophosphamide 2
- Busulfan/Cyclophosphamide (BuCy): 16 mg/kg busulfan plus 120 mg/kg cyclophosphamide 2
- Modified regimens with ATG: Add antithymocyte globulin (6-10 mg/kg Thymoglobuline or 20-40 mg/kg ATG-F) for alternative donor transplants 2
Reduced-Intensity Conditioning (RIC)
RIC regimens are indicated for patients >55 years or those with poor organ function or HSCT-CI ≥3 regardless of age 2. These less toxic regimens include:
- 90-160 mg/m² IV fludarabine
- 6-9 mg/kg oral busulfan (or equivalent IV dose)
- 2-8 Gy TBI
- 80-140 mg/m² IV melphalan
- 5-10 mg/kg IV thiotepa 2
Common RIC combination: Fludarabine 150 mg/m² plus melphalan 140 mg/m² for multiple myeloma 2
Intensified Conditioning
Intensified regimens are reserved for young patients with refractory or relapsed disease 2. These add drugs like cytarabine, etoposide, melphalan, or additional TBI to standard regimens. Example:
- Fludarabine 150 mg/m² (days -10 to -6)
- Cytarabine 5-10 g/m² (days -10 to -6)
- TBI 9 Gy (days -5, -4)
- Cyclophosphamide 120 mg/kg (days -3, -2)
- Etoposide 30 mg/kg (days -3, -2) 2
Critical caveat: Intensified regimens may reduce relapse but increase treatment-related mortality, potentially not improving overall survival 2.
Autologous vs. Allogeneic Differences
Autologous HCT
- Uses patient's own cells harvested before high-dose therapy
- Myeloablative regimens treat the malignancy, followed by cell rescue to restore hematopoiesis 1
- Most common for multiple myeloma, non-Hodgkin lymphoma, Hodgkin lymphoma 1
Allogeneic HCT
- Uses HLA-compatible donor cells
- Conditioning eradicates malignant cells AND induces immunosuppression to prevent graft rejection 1
- Most common for AML, ALL, MDS 1
- ATG is added to prevent graft-versus-host disease (GVHD) in alternative donor transplants 2
Disease-Specific Considerations
For lymphoma: BEAM regimen (BCNU 300 mg/m², etoposide 800 mg/m², cytarabine 800 mg/kg, melphalan 140 mg/m²) 2
For severe aplastic anemia: BuCy+ATG protocol, used as salvage or first-line therapy 2
Common Pitfalls
- Avoid intensified regimens in older patients or those with comorbidities - increased toxicity without survival benefit
- Don't use MAC in patients >55 years unless exceptional performance status - use RIC instead 2
- RIC requires additional immunosuppression and cell therapy to reduce relapse risk 2
- Peripheral blood stem cells have faster engraftment but higher GVHD risk compared to bone marrow grafts 1