Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia.
OBJECTIVE
To evaluate the efficacy and toxicity of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), a dose-intensive regimen, in adult acute lymphocytic leukemia (ALL).


METHODS
Adults with newly diagnosed ALL referred since 1992 were entered onto the study; treatment was initiated in 204 patients between 1992 and January 1998. No exclusions were made because of older age, poor performance status, organ dysfunction, or active infection. Median age was 39.5 years; 37% were at least 50 years old. Mature B-cell disease (Burkitt type) was present in 9%, T-cell disease in 17%. Leukocytosis of more than 30 x 10(9)/L was found in 26%, Philadelphia chromosome-positive disease in 16% (20% of patients with assessable metaphases), CNS leukemia at the time of diagnosis in 7%, and a mediastinal mass in 7%. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and supportive care with antibiotic prophylaxis and granulocyte colony-stimulating factor therapy. Maintenance in patients with nonmature B-cell ALL included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP).


RESULTS
Overall, 185 patients (91%) achieved complete remission (CR) and 12 (6%) died during induction therapy. Estimated 5-year survival and 5-year CR rates were 39% and 38%, respectively. The incidence of CNS relapse was low (4%). Compared with 222 patients treated with vincristine, doxorubicin, and dexamethasone (VAD) regimens, our patients had a better CR rate (91% v 75%, P <.01) and CR rate after one course (74% v 55%, P <.01) and better survival (P <.01), and a smaller percentage had more than 5% day 14 blasts (34% v 48%, P =.01). Previous prognostic models remained predictive for outcome with Hyper-CVAD therapy.


CONCLUSIONS
Hyper-CVAD therapy is superior to our previous regimens and should be compared with established regimens in adult ALL.
Kantarjian
H M
HM
Departments of Leukemia, Biomathematics, and Radiotherapy, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
O'Brien
S
S
Smith
T L
TL
Cortes
J
J
Giles
F J
FJ
Beran
M
M
Pierce
S
S
Huh
Y
Y
Andreeff
M
M
Koller
C
C
Ha
C S
CS
Keating
M J
MJ
Murphy
S
S
Freireich
E J
EJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide