Anthracycline dose intensification in adult acute lymphoblastic leukemia: lack of benefit in the context of the fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimen.
BACKGROUND
In previous studies of frontline therapy for adult acute lymphoblastic leukemia (ALL), early treatment with higher doses of anthracyclines has been reported to improve outcome. The current study was conducted to evaluate whether addition of anthracycline-based consolidation chemotherapy (Course 2) with liposomal daunorubicin (150 mg/m2 intravenously [IV] on Days 1 and 2) and cytarabine (1.5 g/m2 IV on Days 1 and 2) to the standard hyper-CVAD regimen (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high dose methotrexate and cytarabine) would improve outcome.


METHODS
Sixty-eight consecutive adults with de novo ALL or lymphoblastic lymphoma were treated with this modified hyper-CVAD regimen inclusive of rituximab for CD20 expression≥20%.


RESULTS
Sixty-three (93%) patients achieved complete response (CR). With a median follow-up of 90 months, the 5-year CR duration (CRD) and overall survival (OS) rates were 46% and 44%, respectively. Compared with 208 patients treated with standard hyper-CVAD (rates of 45% and 47%, respectively; P=not significant), outcome with the modified hyper-CVAD regimen was not improved overall. Outcome was improved by the addition of rituximab for the CD20-positive subset (rates of CRD and OS of 50% and 53%, respectively), whereas anthracycline intensification worsened outcome for the CD20-negative subset (rates of CRD and OS of 41% and 35%, respectively; P=.01) compared with standard hyper-CVAD. A high mortality rate related to infections in CR was noted among patients aged 60 years or older.


CONCLUSIONS
In the context of the hyper-CVAD regimen, early anthracycline intensification did not improve outcome for adults with de novo ALL or lymphoblastic lymphoma.
Thomas
Deborah
D
Department of Leukemia, Division of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. debthomas@mdanderson.org
O'Brien
Susan
S
Faderl
Stefan
S
Ravandi
Farhad
F
Jabbour
Elias
E
Pierce
Sherry
S
Cortes
Jorge
J
Kantarjian
Hagop
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage*; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D016879:Salvage Therapy; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D018943:Anthracyclines; D003561:Cytarabine; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D008727:Methotrexate; D003630:Daunorubicin