Current strategies for treatment of acute myeloid leukemia at St Jude Children's Research Hospital.
We examined the feasibility of maintaining specific plasma concentrations of ara-C and VP-16 in children with AML. Sixty-one children were treated with 6 sequential cycles of intensive chemotherapy consisting of: (1) cytarabine (ara-C)/VP-16, (2) ara-C/daunorubicin (Dauno), (3) VP-16/amsacrine (m-AMSA), (4) VP-16/5-azacytidine (5-Az), (5) ara-C/Dauno, and (6) ara-C/VP-16. Fifty-nine children had de novo AML, and 2 had a previous myelodysplastic syndrome. The number of patients with each specific FAB subtype was: M0-1; M1-7; M2-24; M3-7; M4-5; M5-11; and M7-6. Simultaneous continuous infusions of ara-C and VP-16 (cycle 1) given at individualized doses to achieve drug plasma concentrations of 1 microM and 30 microM, respectively, produced complete remission (CR) in 26 of 61 patients (43%); an additional 17 patients entered CR after Dauno/ara-C (cycle 2), and one patient required 4 cycles of chemotherapy to achieve CR (total CR rate = 72%). The preliminary 2-year event-free survival (EFS) for patients with FAB-M1 and -M2 AML was only 15% versus 40% for those with FAB-M4 and -M5 AML. Overall, 21 of the 61 patients remain in CR (2-yr EFS = 29%). We conclude that intense treatment with ara-C and VP-16 at doses individualized to achieve target plasma concentrations is feasible although severely myelosuppressive. It results in an acceptable CR rate, but does not improve EFS.(ABSTRACT TRUNCATED AT 250 WORDS)
Hurwitz
C A
CA
St. Jude Children's Research Hospital.
Krance
R
R
Schell
M J
MJ
Santana
V M
VM
Brenner
M K
MK
Ribeirio
R
R
Roberts
W M
WM
Mahmoud
H
H
Belt
J
J
Crom
W
W
D015762:2-Chloroadenosine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000677:Amsacrine / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D017338:Cladribine; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D003839:Deoxyadenosines / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D012074:Remission Induction
D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D000677:Amsacrine; D003561:Cytarabine; D015762:2-Chloroadenosine; D017338:Cladribine; D005047:Etoposide; D001374:Azacitidine; D003630:Daunorubicin