Cytosine arabinoside and mitoxantrone treatment of relapsed or refractory childhood leukemia: initial response and relationship to multidrug resistance gene 1.
The objective of this study was to determine the response rate and toxicity of high-dose cytosine arabinoside (AC) and mitoxantrone (M) in relapsed or refractory childhood acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) and to correlate response with the expression of the multidrug resistance gene 1 (mdr1). Twenty-nine patients were treated with AC 1.0 g/m2 infused over 2 h every 12 h for eight doses (days 1-4) and M 12 mg/m2 infused over 1 h (days 3-6). Mdr1 expression was determined by a polymerase chain reaction (pcr) assay. Ten of 15 patients (67%) with AML obtained a complete remission (CR) of 3 to 30+ months duration. Eight of 14 (57%) ALL patients obtained a CR of 1 to 23+ months duration. The major toxicities were hematopoietic and infectious. Seventy-nine per cent of patients developed a documented infection during induction. Mdr1 did not correlate with a lower induction rate. This AC/M regimen is active in childhood AML and ALL.
Wells
R J
RJ
Children's Hospital Research Foundation, Cincinnati, Ohio.
Odom
L F
LF
Gold
S H
SH
Feusner
J
J
Krill
C E
CE
Waldron
P
P
Moulton
T A
TA
Knoppell
E
E
White
M L
ML
Cairo
M S
MS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D004341:Drug Evaluation; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008942:Mitoxantrone / Q000008:administration & dosage; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D012008:Recurrence; D012074:Remission Induction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D003561:Cytarabine; D008942:Mitoxantrone