| Abstract: |
The outcome of children with acute lymphoblastic leukemia (ALL) and bone marrow relapse has been unsatisfactory largely because of failure to prevent subsequent leukemia relapses. Ninety-six patients were enrolled and received vincristine, prednisone, L-asparaginase, and an anthracycline as reinduction therapy. Ninety-two patients were randomized to receive either daunomycin (DNR) or idarubicin (IDR). After achievement of second complete remission (CR2), maintenance chemotherapy included the same anthracycline, IDR or DNR, high dose cytarabine, and escalating dose methotrexate. Compared to DNR (45 mg/m2/week x 3), IDR (12.5 mg/m2/week x 3) was associated with prolonged myelosuppression and more frequent serious infections. Halfway through the study, the dose of IDR was reduced to 10 mg/m2. Overall, second remission was achieved in 71% of patients. Reinduction rate was similar for IDR and DNR. Reasons for induction failure differed; none of 15, 1 of 5, and 5 of 7 reinduction failures were due to infection for DNR, IDR (10 mg/m2), and IDR (12.5 mg/m2), respectively. Two-year event free survival (EFS) was better among patients who received IDR (12.5 mg/m2) (27 ± 18%) compared to DNR (10 ± 8%, P = 0.05) and IDR (10 mg/m2) (6 ± 12%, P = 0.02). However, after 3 years of follow-up, late events in the high-dose IDR group result in a similar EFS to the lower-dose IDR and DNR groups. In conclusion, DR is an effective agent in childhood ALL. When used weekly at 12.5 mg/m2 during induction, the EFS outcome during the first 2 years of treatment appears better than lower-dose IDR or DNR (45 mg/m2) although this difference was not sustained at longer periods of follow-up. Increased hematopoietic toxicity seen at this dose might be reduced through the use of supportive measures, such as hematopoietins and intestinal decontamination. |
| Keywords: |
cancer survival; child; controlled study; treatment outcome; child, preschool; disease-free survival; major clinical study; prednisone; clinical trial; cancer recurrence; cancer combination chemotherapy; cytarabine; methotrexate; drug megadose; controlled clinical trial; bone marrow; bone marrow suppression; blood toxicity; randomized controlled trial; antineoplastic combined chemotherapy protocols; recurrence; vincristine; acute lymphoblastic leukemia; childhood cancer; daunorubicin; asparaginase; idarubicin; antibiotics, antineoplastic; intravenous drug administration; oral drug administration; intramuscular drug administration; leukemia, lymphocytic, acute, l1; anthracycline antibiotic agent; humans; prognosis; human; male; female; priority journal; article; childhood acute lymphoblastic leukemia; intrathecal drug administration; daunomycin
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