High-dose cytosine arabinoside in combination with mitoxantrone for the treatment of refractory acute myeloid and lymphoblastic leukemia.
In the present study 55 patients with refractory acute myeloid leukemia (AML) (n = 44) and acute lymphoblastic leukemia (ALL) (n = 11) were treated with high-dose cytosine arabinoside (HD-ara-C) and mitoxantrone (HAM) to assess the toxicity and antileukemic activity of the two-drug combination. All patients had received a standardized first-line therapy according to the corresponding multicenter trials of the German AML and ALL cooperative groups and were considered refractory to conventional treatment. Therapy consisted of HD-ara-C 3 g/m2 every 12 hours on days 1 to 4; mitoxantrone was started at 12 mg/m2/d on days 3, 4, and 5 and was escalated to four and five doses of 10 mg/m2/d on days 2 to 5 and 2 to 6. From the 44 patients with AML, 24 (54%) achieved a complete remission, two a partial remission, and five were nonresponders. Thirteen patients died of infections (n = 11), pericardiac effusion, or acute cardiomyopathy. In refractory ALL, seven of 11 patients (64%) went into a complete remission, one patient was resistant, and three patients were early deaths. Nonhematologic side effects consisted predominantly of nausea and vomiting, mucositis, and diarrhea. More severe CNS symptoms were encountered during five treatment courses. The median time to complete remission was 36 days. Excluding five patients who underwent bone marrow transplantations, the median remission duration was 4.5 months in AML and 2.3 months in ALL. The median survival time was three months for all patients and nine months for responders only. These data emphasize a high antileukemic activity of HAM in refractory AML and ALL and support the incorporation of the HAM regimen into first-line treatment.
Hiddemann
W
W
Kreutzmann
H
H
Straif
K
K
Ludwig
W D
WD
Mertelsmann
R
R
Planker
M
M
Donhuijsen-Ant
R
R
Lengfelder
E
E
Arlin
Z
Z
Büchner
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000009:adverse effects; D013866:Thioguanine / Q000008:administration & dosage
D003561:Cytarabine; D008942:Mitoxantrone; D013866:Thioguanine; D003630:Daunorubicin