Acute Leukemias - Republican Scientific Medical Library

a 12.2 · The Hyper-CVAD Regimen in Adult ALL 163
Table 12.1. Outline of the hyper-CVAD regimen
Therapy stage Dose and schedule
Induction and intensified Hyper-CVAD (courses 1, 3, 5, and 7)
consolidation
– Cyclosphosphamide 300 mg/m 2 i.v. over 3 h q 12 h for 6 doses on days 1–3
– Mesna 600 mg/m 2 as a continuous i.v. continuous infusion over 24 h daily on days 1–3
(starting with cyclophosphamide and finishing 6 h after the last dose)
– Doxorubicin 50 mg/m 2 i.v. continuous infusion over 24 h on day 4
– Vincristine 2 mg i.v. days 4 and 11
– Dexamethasone 40 mg/day days 1–4, and 11–14
Methotrexate (MTX) and high-dose cytarabine (courses 2, 4, 6, and 8)
– MTX 200 mg/m 2 i.v. over 2 h followed by 800 mg/m 2 i.v. over 22 h on day 1
– Citrovorum factor rescue 15 mg q 6 h for 8 doses (starting 24 h after completion of MTX)
– Cytarabine 3 g/m 2 i.v. over 2 h q 12 h for 4 doses on days 2 and 3
– Methylprednisolone 50 mg i.v. twice daily on days 1–3
CNS prophylaxis IT MTX 12 mg on day 2 and cytarabine 100 mg on day 7 of each course
Low- risk patients: 4 IT (courses 1–2)
Standard and unknown-risk patients: 8 IT (courses 1–4)
High-risk patients: 16 IT (courses 1–8)
Maintenance therapy POMP
– 6-mercaptopurine 50 mg orally three times per day
– MTX 20 mg/m 2 orally weekly
– Prednisone 200 mg orally days 1–5 q month
– Vincristine 2 mg i.v. q month
Supportive care – Antibiotic prophylaxis (e.g., levaquin, fluconazole, valacylovir)
– Hematopoietic growth factor support during induction and consolidation
– Use of laminar air flow rooms (patients ³60 years of age)
mains a mainstay of the hyper-CVAD regimen. As
among 35 patients with “unknown CNS risk” who received
eight IT injections none experienced a CNS relapse,
and as among 51 patients with low-risk for CNS
relapse, the CNS relapse rate was 6%, the number of
IT therapies was changed to six for low-risk disease,
and eight for all other risk categories except mature B
ALL where patients still receive 16 IT treatments. Because
of late relapses, maintenance was extended to
3 years. In addition, two intensification courses of hyper-CVAD
followed by methotrexate and L-asparaginase,
each, at months 6 and 18 of maintenance were
added. Thomas, et al. demonstrated that expression of
CD20 has been associated with a worse prognosis with
both conventional [e.g., vincristine, adriamycin, dexa-
methasone (VAD)], or intensive ALL therapy (hyper-
CVAD) [10]. Of 324 patients with de novo ALL (mature
B ALL excluded) and of whom complete flow cytometry
data were available, 120 cases (37%) were CD20-positive
(defined as > 20% expression by flow cytometry).
Although remission rates were comparable, 3-year remission
duration (28% vs. 58% with hyper-CVAD;
p = 0.02) and 3-year survival (27% vs. 52%; p