Six months of maintenance chemotherapy after intensified treatment for acute lymphoblastic leukemia of childhood

Citation
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
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
JOURNAL OF CLINICAL ONCOLOGY
ISSN journal
0732-183X → ACNP
Volume
18
Issue
7
Year of publication
2000
Pages
1508 - 1516
Database
ISI
SICI code
0732-183X(200004)18:7<1508:SMOMCA>2.0.ZU;2-R
Abstract
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.