• hyperfractionated cyclophosphamide;
  • vincristine;
  • doxorubicin;
  • and dexamethasone (Hyper-CVAD) regimen;
  • acute lymphocytic leukemia (ALL);
  • long-term follow-up



Modern intensive chemotherapy regimens have improved the prognosis for patients with adult acute lymphocytic leukemia (ALL). With these regimens, the complete response rates are now reported to be > 80%, and the long-term survival rates range from 30% to 45%. The current analysis updated the long-term results with the original hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) program, with a median follow-up time of 63 months.


Between 1992 and 2000, 288 patients were treated with Hyper-CVAD. The median age of the patients was 40 years, and 59 patients (20%) were ≥ age 60 years. The incidence of Philadelphia chromosome (Ph)-positive ALL was 17%, and the incidence of of T-cell ALL was 13%.


A complete response (CR) was achieved in 92% of patients. The induction mortality rate was 5% (2% if the patient's age was < 60 years, and 15% if the patient's age was ≥ 60 years). With a median follow-up time of 63 months, the 5-year survival rate was 38% and the 5-year CR duration rate was 38%. Multivariate analysis of prognostic factors for CR duration identified the following adverse factors: age ≥ 45 years, leukocytosis ≥ 50 × 109/L, poor performance status (an Eastern Cooperative Oncology Group score of 3–4), Ph-positive disease, French–American–British L2 morphology, > 1 course to achieve CR, and Day 14 bone marrow blasts > 5%. Patients were divided into low-risk (risk score 0–1; 37%), intermediate risk (risk score 2–3; 36%), and poor-risk groups (risk score ≥ 4; 27%) with 5-year CR duration rates of 52%, 37%, and 10%, respectively.


Compared with the previous VAD regimens, Hyper-CVAD was associated with significantly better CR rates, CR duration, and survival. The long-term follow-up results of Hyper-CVAD were favorable. Comparison of Hyper-CVAD with other established adult ALL regimens is warranted. Cancer 2004. © 2004 American Cancer Society.