To improve the complete remission rate of acute leukemia, especially that of acute myelogenous leukemia, 4 agents each of which has an established but limited effect on acute leukemia were combined. Drugs used were daunomycin 25 mg/m
2 iv, cytosine arabinoside 80 mg/m
2 iv (1 hour infusion), 6 mercaptopurine-riboside 300 mg/m
2 iv and prednisolone 60 mg/m
2 po. The combination chemotherapy was administered daily in a 4 day course, repeated every 2 weeks. Three courses were administered before it was decided as ineffective.
As of April 1972, 34 patients (32 adults and 2 children) had been studied: acute myeloblastic leukemia (AML), 16 cases; paramyeloblastic (AMpL), 9 cases; monocytic (AMoL), 8 cases and lymphocytic (ALL) 1 case (The ALL case was refractory to daunomycin+vincristin+prednisolone therapy).
Of 34 patients 22 (64.7%) obtained complete and 3 (8.8%) partial remissions. There was no difference in the complete remission (CR) rate between previously treated and untreated patients, CR rate being 6/9 (66.7%) and 16/25 (64.0), respectively. The CR rate in each type of acute leukemia was 11/16 (68.8%) in AML, 3/9 (33.3%) in AMpL, 7/8 (87.5%) in AMoL and 1/1 in ALL. The median survival of 25 previously untreated patients is 5 2/3 (1/3∼16) months.
Twelve out of 23 adults with AGL (AML+AMpL) had complete remissions (CR rate 52.5%). CR rate among 31 adults with acute non-lymphocytic leukemia (AML+AMpL+AMoL) was 61.3%.
CR was obtained after only 1 or 2 courses of treatment in 19/22 patients. The median duration until CR was 32 days from the beginning of the treatment (14∼64 days). The median remission length currently is 5+months.
A profound aplastic bone marrow ensued even in those patients who did not reach CR, indicating a potent leukemocidal effect of the regimen.
Toxic effects of the treatment so far observed includes severe pancytopenia, nausea, vomiting, epilation and liver function abnormalities. As many as 32 among 34 patients showed fever above 38°C some time during the remission induction treatment most likely due to infections. However, only two of them succumbed to the infection.
The quadruple combination chemotherapy reported here proved to be one of the most potent remission induction therapy of acute leukemia so far reported.
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