Y. Toyoda et al., Six months of maintenance chemotherapy after intensified treatment for acute lymphoblastic leukemia of childhood, J CL ONCOL, 18(7), 2000, pp. 1508-1516
Purpose: We postulated that intensification of chemotherapy immediately aft
er remission induction might reduce the leukemic cell burden sufficiently t
o allow an abbreviated period of antimetabolite therapy.
Patients and Methods: Three hundred forty-seven children (ages 1 to 15 year
s) with previously untreated acute lymphoblastic leukemia (ALL) were enroll
ed onto the Tokyo L92-13 study, which excluded patients with mature B-cell
ALL and patients less than 1 year old. One hundred twenty-four patients wer
e classified as standard risk, 122 as high risk, and 101 as extremely high
risk, according to age, peripheral-blood leukocyte count selected genetic a
bnormalities, and immunophenotype. All subjects received four drugs for rem
ission induction, followed by a risk-directed multidrug intensification pha
se and therapy for presymptomatic leukemia in the CNS. Maintenance chemothe
rapy with oral mercaptopurine and methotrexate was administered for 6 month
s, with all treatment stopped by 1 year after diagnosis.
Results: The mean (+/- SD) event-free survival (EFS) and overall survival r
ates far all patients were 59.5% +/- 3.4% and 81.5% +/- 2.2%, respectively,
at 5.5 years after diagnosis. EFS rates by risk category were similar (60.
2% +/- 6.0% for standard risk, 57.7% +/- 5.6% for high risk, and 62.5% +/-
5.7% for extremely high risk), whereas overall survival rates differed sign
ificantly (91.2% +/- 2.7%, 80.0% +/- 4.1%, and 72.1% +/- 4.5%, respectively
, P < .0001 by the lag-rank test). There were 107 relapses. Eighty-five (79
.4%) of these 107 patients achieved second complete remissions, with subseq
uent EFS rates of 61.5% +/- 7.9% (standard risk), 42.6% +/- 8.1% (high risk
), and 9.6% +/- 6.4% (extremely high risk). Of the five risk factors analyz
ed, only the response to prednisolone monotherapy among extremely high-risk
patients proved important.
Conclusion: Early treatment intensification did nat compensate for a trunca
ted phase of maintenance chemotherapy in children with standard or high-ris
k ALL, However, 6 months of antimetabolite treatment seemed adequate for ex
tremely high-risk patients who were good responders to prednisolone and rec
eived intensified chemotherapy that included high-dose cytarabine early in
the clinical course. (C) 2000 by American Society of Clinical Oncology.