High-dose cytosine arabinoside: treatment and cellular pharmacology of chronic myelogenous leukemia blast crisis.
Twenty-one patients with chronic myelogenous leukemia (CML) in blastic transformation underwent 22 remission induction attempts with high-dose cytosine arabinoside (ara-C), administered as a two-hour infusion of 3 g/m2 for six to 12 doses. Ara-C doses were administered every 12 hours in 15 patients and every six to ten hours in six patients. Median patient age was 35 years (range, 20 to 62). The median duration of benign phase was 25 months (range, 0 to 167). Morphology of blast crisis blast cells was myeloid in 15 patients and lymphoid in six. Five patients achieved complete remission (CR), three had partial remission (PR), and one had hematologic improvement, for an overall response rate of 41%. Median remission duration was 2.5 months (range, 0.5 to 6 months). Survival duration was 6 months for responding patients and 1.5 months for those with resistant disease. The response rate was similar for patients with myeloid and lymphoid blast crisis (31% v 50%, respectively). The response rate was significantly higher for patients whose benign phase was less than 1 year (75% v 21%, P = .05) and who had prolonged marrow aplasia after ara-C (86% v 27%, P = .05). Myelosuppression was the major dose-limiting toxicity, and cerebellar toxicity occurred in two patients. Intracellular ara-C 5'-triphosphate (ara-CTP) levels were similar in blood and bone marrow leukemic cells and were slightly greater in the cells of responding patients compared to those with resistant disease. We conclude that high-dose ara-C is an effective regimen for CML blast crisis, resulting in a substantial response rate but modest remission duration. Its combination with other agents may further improve the prognosis of patients with this resistant disease.
Iacoboni
S J
SJ
Plunkett
W
W
Kantarjian
H M
HM
Estey
E
E
Keating
M J
MJ
McCredie
K B
KB
Freireich
E J
EJ
D000328:Adult; D001927:Brain Diseases / Q000139:chemically induced; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D004341:Drug Evaluation; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007239:Infections / Q000150:complications; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors
D003561:Cytarabine