What is HyperCVAD (Hyperfractionated Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone) induction treatment?

HyperCVAD Induction Treatment

HyperCVAD is an intensive chemotherapy regimen for acute lymphoblastic leukemia (ALL) consisting of 8 alternating cycles: Cycle A (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with Cycle B (high-dose methotrexate and cytarabine), administered over 5-6 months with mandatory CNS prophylaxis. 1, 2

Regimen Structure

Cycle A Components (HyperCVAD)

• Cyclophosphamide: 300 mg/m² IV twice daily on days 1-3 (total 6 doses, hyperfractionated) 2
• Vincristine: 2 mg IV on days 4 and 11 1
• Doxorubicin (Adriamycin): Standard dosing as part of the regimen 3, 4
• Dexamethasone: 40 mg PO or IV daily on days 1-4 and 11-14 1

Cycle B Components

• Methotrexate: 1 g/m² IV over 24 hours on day 1 1
• Cytarabine: 3 g/m² IV over 2 hours every 12 hours for 4 doses on days 2-3 1

Treatment Duration

• Total of 8 cycles (4 cycles of A alternating with 4 cycles of B) administered over 5-6 months 3, 5

CNS Prophylaxis (Mandatory Component)

• Intrathecal methotrexate 12 mg and/or cytarabine 100 mg on day 2 of each cycle 1
• Alternative triple intrathecal therapy (methotrexate, cytarabine, hydrocortisone) is also recommended 1
• CNS prophylaxis is integrated throughout induction and consolidation phases 3

Disease-Specific Modifications

CD20-Positive B-Cell ALL

• Add rituximab 375 mg/m² IV on days 1 and 11 of each Cycle A and day 2 of each Cycle B 1
• This modification improves 3-year complete remission duration to 67% and overall survival to 61% 1

Philadelphia Chromosome-Positive ALL

• Add tyrosine kinase inhibitor starting day 1 of cycle 1: imatinib 600 mg daily or dasatinib 140 mg daily 1

Elderly Patients (≥60 years)

• Dose reductions of 25-33% in cyclophosphamide and doxorubicin doses are recommended 1
• Higher induction mortality (15% vs. 2% in younger patients) necessitates careful monitoring 2

Supportive Care Requirements

• G-CSF 5 mcg/kg SC daily starting 24 hours after chemotherapy completion until ANC >1,000/μL 1
• Mandatory hepatitis B screening with HBsAg and anti-HBc before treatment initiation 1
• Antibiotic prophylaxis during neutropenic periods 5

Maintenance Therapy

Following completion of 8 intensive cycles, maintenance therapy is administered for 2-3 years: 1, 2

• Methotrexate 10 mg/m² PO weekly 1
• 6-mercaptopurine 50 mg PO three times daily 1
• Vincristine/prednisone pulses monthly 1

Expected Outcomes

Complete Remission Rates

• Overall CR rate: 81-92% 1, 5
• CR after first course: 74% 5

Survival Outcomes

• 5-year overall survival: 38-52% 1, 6, 5
• 3-year progression-free survival: 66% 7
• Median overall survival: 32 months 1

CNS Relapse

• Low CNS relapse rate: 4% due to intensive intrathecal prophylaxis 5

Clinical Context and Comparisons

• HyperCVAD is considered less complex than CALGB regimens while maintaining comparable efficacy 3
• The regimen shows similar outcomes to BFM-like regimens in head-to-head comparisons, with 3-year OS of 71.9% vs. 76.9% respectively 8
• It is particularly effective in younger adults (<60 years) with fewer comorbidities 2
• The regimen is also used for other hematologic malignancies including lymphoblastic lymphoma, Burkitt's lymphoma, and mantle cell lymphoma 3, 7, 4

Common Pitfalls and Caveats

• Induction mortality risk: 6% overall, but increases to 15% in patients ≥60 years 2, 5
• Myelosuppression: Requires aggressive G-CSF support and monitoring 2
• Hepatotoxicity: Consider TPMT gene polymorphism testing before 6-mercaptopurine maintenance 2
• Mediastinal disease: May require consolidative radiation therapy 7
• CNS disease at presentation: Associated with worse outcomes and requires intensified intrathecal therapy 7