Table 1.
Hyper-CVAD and Modified Hyper-CVAD Chemoimmunotherapy Regimens
| Regimen | Modified Hyper-CVAD 1 and 2 (± rituximab) |
Standard Hyper-CVAD (1992-1999) | |
|---|---|---|---|
| 2: Without Intensification (2001-present) | 1: With Intensification (2000-2001) | ||
| Induction | |||
| Hyper-CVAD | Y | Y | Y |
| Laminar air flow rooms if age ≥ 60 years | Y | Y | N |
| Rituximab 375 mg/m2 IV days 1, 11 if CD20 ≥ 20% | Y | Y | N |
| Consolidation | |||
| Cycle 2 (anthracycline intensification) | |||
| LDNR 150 mg/m2 IV over 12 h days 1-2 | N | Y | N |
| Cytarabine 1.5 g/m2 CI IV daily days 1-2 | |||
| Prednisone 200 mg PO days 1-5 | |||
| Cycles 2, 4, 6, 8 or cycles 3, 5, 7, 9 | |||
| MTX 200 mg/m2 IV over 2 h, then 800 mg/m2 IV over 22 h day 1 | Y | Y | Y |
| Cytarabine 3 g/m2 (1 g/m2 if age ≥ 60) IV over 2 h every 12 h × 4 doses on days 2-3 | |||
| Solu-Medrol 50 mg IV every 12 h × 6 doses on days 1-3 | |||
| Leucovorin 50 mg IV 12 h after end MTX then 15 mg IV every 6 h × 8 doses or until MTX level < 0.1 μmol/L | |||
| Acetazolamide if urine pH < 7 | |||
| Cycles 1, 3, 5, 7 or cycles 1, 4, 6, 8 | |||
| Cyclophosphamide 300 mg/m2 IV over 2 h every 12 h × 6 doses on days 1-3 | Y | Y | Y |
| Mesna 600 mg/m2 CI IV daily days 1-3 | |||
| Dexamethasone 40 mg IV or PO days 1-4, 11-14 | |||
| Doxorubicin 50 mg/m2 CI IV over 2-24 h day 4 (48 h if EF < 50%) | |||
| VCR 2 mg IV days 1,11 | |||
| Cycles 1-4 | |||
| If CD20 ≥ 20%: 8 doses rituximab 375 mg/m2 IV | Y | Y | N |
| Days 1, 11 (hyper-CVAD) | |||
| Days 1, 8 (LDNR- or MTX-cytarabine) | |||
| CNS prophylaxis | |||
| MTX 12 mg (6 mg if Ommaya) day 2 | Y | Y | |
| Cytarabine 100 mg day 7 or 8 | |||
| No. of ITs | |||
| Liposomal cytarabine in modified hyper-CVAD 2 (n = 32)24 | Y | N | |
| Risk adapted (LDH ≥ 1,400 U/L, S + G2M ≥ 14%) | |||
| High (one elevated) | 8 | 16 | |
| Indeterminate (one unknown) | 8 | 8 | |
| Low | 6 | 4 | |
| Maintenance | |||
| Oral POMP (6-mercaptopurine, VCR, MTX, prednisone) | Months 1-5, 8-17, 20-30 | Months 1-6, 8-10, 12-24 | |
| Intensification | |||
| Hyper-CVAD (plus rituximab 375 mg/m2 IV days 1, 11 if CD20 ≥ 20%) | Months 6, 18 | N | |
| Intensification† | |||
| MTX 100 mg/m2 IV day 1 weekly × 4 | Months 7, 19 | Months 7, 11 | |
| L-asparaginase 20,000 units IV day 2 weekly × 4 | |||
| Supportive care | |||
| IV/oral alkalinzation all courses; rasburicase/allopurinol for induction | |||
| G-CSF 10 μg/kg subcutaneously daily until ANC > 109/L; pegfilgastrim 6 mg subcutaneously could be substituted after 2007 | |||
| Duration of doxorubicin infusions increased for modified hyper-CVAD regimens for cardioprotection | |||
| Leucovorin rescue: 50-100 mg IV every 4-6 h if MTX levels were elevated at the end of infusion [0 h, confirmed on repeat sample] to greater than 20 μmol/L, > 1 μmol/L at 24 h, or > 0.1 μmol/L at 48 h | |||
Abbreviations: Hyper-CVAD, fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone; Modified hyper-CVAD 1, anthracycline intensification with or without rituximab; Modified hyper-CVAD 2, no anthracycline intensification with or without rituximab; Y, yes; N, no; IV, intravenous; LDNR, liposomal daunorubicin; h, hour; CI, continuous infusion; PO, by mouth; MTX, methotrexate; EF, ejection fraction; VCR, vincristine; IT, intrathecal treatments; LDH, lactate dehydrogenase; S + G2M, proliferative index; POMP, 6-mercaptopurine, VCR, MTX, and prednisone; G-CSF, granulocyte colony-stimulating factor; ANC, absolute neutrophil count.
Refer to online-only Appendix for further details including guidelines for dosing modifications.
For standard hyper-CVAD17 prior to July 2000 etoposide 100 mg/m2 IV days 1-5, pegylated asparaginase 2,500 U/m2 day 1 months 9, 12.