Hyperfractionated cyclophosphamide, vincristine (VNC), doxorubicin, and dexamethasone (hyper-CVAD), developed in 1992, became the mainstay in the treatment of acute lymphoblastic leukemia (ALL). The combination included eight courses of intensive therapy with hyper-CVAD alternating with high-dose methotrexate (MTX) and cytarabine (Ara-C) followed by 2.5 to 3 years of maintenance therapy. Multiple modifications have been made to optimize outcomes and assist in reducing both short- and long-term adverse effects.
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