There are two categories of HSCT, autologous HSCT (ASCT) and allogeneic HSCT (allo-SCT). For patients being considered for ASCT, the most common reason for choosing a particular conditioning regimen is the disease for which transplantation is being considered. For patients being considered for allo-SCT, the initial choice of a conditioning regimen is based on the disease and the condition of the recipient at the time of transplantation. And a major consideration for allo-SCT is whether to administer a myeloblative conditioning regimen or a reduced-intensity regimen.
When choosing between myeloablative or reduced-intensity conditioning, providers analyze a number of factors, including the age, the comorbidities, the disease and its stage at the time of transplantation, the source of stem cells being used, the degree to which human leukocyte antigen matches, and the preference of the patient.
To evaluate the efficacy and safety of different conditioning regimens, five aspects should be considered, including toxicity, risk of relapse, hematopoietic engraftment, treatment-related mortality, and overall survival.
Conditioning Regimens for ASCT
Table 1 Conditioning Regimens and Specific Malignancy
|Conditioning Regimen||Specific Malignancy|
|1||Gemcitabine plus busulfan plus melphalan||Relapsed non-Hodgkin lymphoma|
|2||Gemcitabine plus busulfan plus melphalan||Refractory Hodgkin lymphoma|
|3||Busulfan plus cyclophosphamide plus etoposide||non-Hodgkin or Hodgkin lymphoma|
|4||Busulfan plus bortezomib||Multiple myeloma (relapse after first ASCT)|
1. Gemcitabine/Busulfan/Melphalan for relapsed non-Hodgkin lymphoma
Gemcitabine, intravenous infusion over 4.5 hrs per day with a total dose of 2550 mg/m2 per day (maximum tolerated dose). Busulfan, intravenously in 4 daily doses targeted to an area under the curve (AUC) of 4000 μM*min per day. Melphalan, on days minus 3 and minus 2, 60 mg/m2 per day.
2. Gemcitabine/Busulfan/Melphalan for refractory Hodgkin lymphoma
Gemcitabine, intravenous infusion for 10 mg/m2 per minute over 4.5 hrs on days minus 8 and minus 3. Busulfan, intravenously targeted to an AUC of 4000 μM*min per day for 4 daily doses. Melphalan, given at 60 mg/m2 per day for 2 days on days minus 3 and minus 2.
3. Busulfan/Cyclophosphamide/Etoposide for non-Hodgkin or Hodgkin lymphoma
Busulfan, infusion at a test dose of 0.8 mg/kg for 2 hrs between days minus 14 and minus 11. The test dose is used for pharmacokinetic testing. The remaining busulfan dose is calculated to achieve a total AUC of 20,000 μM*min. One-fourth of this dose is given as a 3-hour infusion on day minus 8, during which a second pharmacokinetic analysis is done. The same daily busulfan dose is administered on days minus 7, minus 6, and minus 5, unless the pharmacokinetic results for day minus 8 showed total AUC outside the target range plus or minus 20%. Etoposide is administered at a dose of 1400 mg/m2 on day minus 4 followed by cyclophosphamide 2.5 g/m2 per day on days minus 3 and minus 2.
4. Busulfan/Bortezomib for mutiple myeloma
Busulfan, infusion at a test dose of 0.8 mg/kg for 2 hrs between days minus 12 and minus 9. Following pharmacokinetic sampling, individualized pharmacokinetic-directed dosing of busulfan is recommended to achieve a total AUC for the regimen of 20,000 μM*min, with intravenous infusion over 3 hrs each day from days minus 5 to minus 2. Bortezomib is administered 1.3 mg/m2 intravenously on day minus 1.
5. Melphalan for mutiple myeloma
High-dose melphalan forms the backbone of the conditioning regimen for the vast majority of patients undergoing ASCT for multiple myeloma. However, patients given the same elevated dose of melphalan may experience up to 5-fold variation in total exposure as measured by AUC. The median dose of melphalan is 192 mg/m2.
Conditioning Regimens for allo-SCT
Table 2 Conditioning Regimens and Specific Diseases
|Conditioning Regimen||Specific Diseases|
|1||Busulfan plus fludarabine||Variety of hematological malignancies|
|2||Fludarabine plus busulfan||Malignant and non-malignant diseases (pediatric)|
|3||Fludarabine plus busulfan||Lymphoma|
1. Busulfan/Fludarabine for variety of hematological malignancies
Busulfan, a test dose of intravenous busulfan 0.8 mg/kg is administered approximately 1 week prior to the start of conditioning, and a desired AUC is calculated from the busulfan clearance dose levels. Dose levels are escalated in 20% increments from 4800 to 5766 to 7603 and finally to 8663 μM*min per 24 hours, from days minus 7 to day minus 3. The infusion is given over 90 hours all together. Fludarabine is administered 30 mg/m2 per day on days minus 7 to minus 3.
2. Fludarabine/Busulfan for malignant and non-malignant diseases (pediatric)
3. Fludarabine/Busulfan for lymphoma
Busulfan is targeted to three levels of AUC of 3500 μM*min per day, 5300 μM*min per day, and over 5300 μM*min per day. All three groups are along with intravenous fludarabine.
Reduced-Intensity Conditioning Regimen
1. Fludarabine plus cyclophosphamide, with or without anti-thymocyte globulin for severe aplastic anemia.
2. 2 Gy total body irradiation alone or with fludarabine for hematological malignancies.
3. Clofarabine plus total lymphocyte irradiation plus anti-thymocyte globulin for variety of hematological malignancies.
4. Alemtuzumab alone for relapsed/refractory chronic lymphocytic leukemia.