Schema of prioritized regimen for nonmyeloablative, HLA-mismatched unrelated BMT
| Day . | Drug and adult dosing* . |
|---|---|
| Days –6 through –2 | Fludarabine 30 mg/m2 IV qd (adjusted for renal function) |
| Days –6 and –5 | Cyclophosphamide 14.5 mg/kg IV qd |
| Day –1 | Total body irradiation, 200 cGy |
| Day 0 | Infuse T-cell replete bone marrow† |
| Begin infection prophylaxis (no voriconazole) | |
| Days 3 and 4 | Cyclophosphamide 50 mg/kg IV qd over 1-2 h with hydration‡ |
| Mesna 40 mg/kg IV qd in divided doses | |
| Day 5§ | Sirolimus loading dose: 6 mg po once |
| Begin MMF 15 mg/kg po tid (maximum 3 g/day) | |
| Begin filgrastim 5 µg/kg SC or IV qd (until ANC ≥1000/µL for 3 d) | |
| Day 6 | Begin sirolimus 2 mg po qd; adjust to maintain trough of 5-12 ng/mL |
| Day 35 | Discontinue MMF after last dose‖ |
| Day 180 | Discontinue sirolimus after last dose‖ |
| Day . | Drug and adult dosing* . |
|---|---|
| Days –6 through –2 | Fludarabine 30 mg/m2 IV qd (adjusted for renal function) |
| Days –6 and –5 | Cyclophosphamide 14.5 mg/kg IV qd |
| Day –1 | Total body irradiation, 200 cGy |
| Day 0 | Infuse T-cell replete bone marrow† |
| Begin infection prophylaxis (no voriconazole) | |
| Days 3 and 4 | Cyclophosphamide 50 mg/kg IV qd over 1-2 h with hydration‡ |
| Mesna 40 mg/kg IV qd in divided doses | |
| Day 5§ | Sirolimus loading dose: 6 mg po once |
| Begin MMF 15 mg/kg po tid (maximum 3 g/day) | |
| Begin filgrastim 5 µg/kg SC or IV qd (until ANC ≥1000/µL for 3 d) | |
| Day 6 | Begin sirolimus 2 mg po qd; adjust to maintain trough of 5-12 ng/mL |
| Day 35 | Discontinue MMF after last dose‖ |
| Day 180 | Discontinue sirolimus after last dose‖ |
ANC, absolute neutrophil count; MMF, mycophenolate mofetil; po, by mouth; qd, once daily; SC, subcutaneous; tid, three times daily.
Dose cyclophosphamide and mesna using the lesser of ideal and actual body weight. Dose fludarabine and MMF using actual body weight.
Harvest donor bone marrow with a target yield of 4 × 108 nucleated cells/kg recipient’s ideal body weight; the lowest acceptable yield is 1.5 × 108 nucleated cells/kg.
Day 3 cyclophosphamide is ideally given 60-72 h after graft infusion.
No systemic immunosuppressive agents, including corticosteroid anti-emetics, are to be given until at least 24 h after completion of all cyclophosphamide.
Optional if graft-versus-host disease is present.