Results of the vincristine, doxorubicin, and dexamethasone regimen in adults with standard- and high-risk acute lymphocytic leukemia.
One hundred five untreated adult patients with acute lymphocytic leukemia (ALL) were entered on the vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and Decadron (dexamethasone; Merck Sharp and Dohme, West Point, PA) (VAD) regimen. Induction therapy with VAD and VAD plus cyclophosphamide (CVAD) was followed by a 2-year rotating maintenance program with multiple antileukemic combinations, and included early intensifications with Adriamycin and high-dose cytarabine (ara-C) and a late intensification with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologous bone marrow transplantation (BMT). Duration of therapy was 24 to 30 months. Eight-eight patients (84%) achieved complete remission (CR) with VAD-CVAD, and 94 (90%) ultimately had CR with continuation of the maintenance as planned. Induction mortality was 3%; only half of the patients required prolonged hospitalization of 1 week or longer, or intravenous antibiotics. Maintenance therapy was given to 79 patients, while nine with histocompatibility locus antigen (HLA)-matched related donors underwent allogeneic BMT. The median remission duration was 22 months, and the median survival was 19 months. Factors associated with significantly worse CR rates were older age, the presence of hypoalbuminemia or hyperbilirubinemia, L2 or L3 morphology, and myeloid markers on leukemic cells. Those associated with significantly worse remission durations were the presence of elevated leukocyte or absolute peripheral blast counts, Philadelphia chromosome (Ph)-positive or B-cell ALL, L2 morphology, and more than one course to achieve CR. Patients could be divided into standard-risk ALL (28% of patients) and high-risk ALL (72% of patients) with long-term remission rates of 70% versus less than 30%. The 26 patients who underwent CBV autologous BMT had similar long-term outcome compared with 21 patients who did not (older age, medical contraindications, or socioeconomic problems). The presence or absence of myeloid markers on leukemic cells did not affect long-term prognosis. We conclude that VAD therapy is a well-tolerated effective induction regimen. High-risk ALL patients require alternative maintenance investigational approaches.
Kantarjian
H M
HM
Department of Hematology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
Walters
R S
RS
Keating
M J
MJ
Smith
T L
TL
O'Brien
S
S
Estey
E H
EH
Huh
Y O
YO
Spinolo
J
J
Dicke
K
K
Barlogie
B
B
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols; D016026:Bone Marrow Transplantation; D002330:Carmustine / Q000008:administration & dosage / Q000633:toxicity; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity; D003561:Cytarabine / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage / Q000633:toxicity; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity; D005047:Etoposide / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000628:therapy; D012307:Risk Factors; D014750:Vincristine / Q000008:administration & dosage / Q000633:toxicity
D000970:Antineoplastic Agents; D003561:Cytarabine; D014750:Vincristine; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D002330:Carmustine