Mitoxantrone and cytarabine induction, high-dose cytarabine, and etoposide intensification for pediatric patients with relapsed or refractory acute myeloid leukemia: Children's Cancer Group Study 2951.
OBJECTIVE
To evaluate the response rate, survival, and toxicity of mitoxantrone and cytarabine induction, high-dose cytarabine and etoposide intensification, and further consolidation/maintenance therapies, including bone marrow transplantation, in children with relapsed, refractory, or secondary acute myeloid leukemia (AML). To evaluate response to 2-chlorodeoxyadenosine (2-CDA) and etoposide (VP-16) in patients who did not respond to mitoxantrone and cytarabine.


METHODS
Patients with relapsed/refractory AML (n = 101) and secondary AML (n = 13) were entered.


RESULTS
Mitoxantrone and cytarabine induction achieved a remission rate of 76% for relapsed/refractory patients and 77% for patients with secondary AML, with a 3% induction mortality rate. Cytarabine and etoposide intensification exceeded the acceptable toxic death rate of 10%. The response rate of 2-CDA/VP-16 was 8%. Two-year overall survival was estimated at 24% and was better than historical control data. Patients with secondary AML had similar outcomes to relapsed or refractory patients. Initial remission longer than 1 year was the most important prognostic factor for patients with primary AML (2-year survival rate, 75%), whereas for patients with primary AML, with less than 12 months of initial remission, survival was 13% and was similar to that of refractory patients (6%).


CONCLUSIONS
Mitoxantrone and cytarabine induction is effective with reasonable toxicity in patients with relapsed/refractory or secondary AML. The cytarabine and etoposide intensification regimen should be abandoned because of toxicity. Patients with relapsed AML with initial remissions longer than 1 year have a relatively good prognosis.
Wells
Robert J
RJ
MD Anderson Cancer Center, Houston, TX, USA. rjwells@mdanderson.org.
Adams
Mary T
MT
Alonzo
Todd A
TA
Arceci
Robert J
RJ
Buckley
Jonathan
J
Buxton
Allen B
AB
Dusenbery
Kathryn
K
Gamis
Alan
A
Masterson
Margaret
M
Vik
Terry
T
Warkentin
Phyllis
P
Whitlock
James A
JA
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
D003561:Cytarabine; D005047:Etoposide; D008942:Mitoxantrone