Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leukemia, 1984-1999.
We report the long-term results of Tokyo Children's Cancer Study Group's studies L84-11, L89-12, L92-13, and L95-14 for 1846 children with acute lymphoblastic leukemia, which were conducted between 1984 and 1999. The value of event-free survival (EFS)+/-s.e. was 67.2+/-2.2% at 10 years in L84-11, which was not improved in the following two studies, and eventually improved to 75.0+/-1.8% at 10 years in L95-14 study. The lower EFS of the L89-12 reflected a high rate of induction failure because of infection and delayed remission in very high-risk patients. The L92-13 study was characterized by short maintenance therapy; it resulted in poor EFS, particularly in the standard-risk (SR) group and boys. Females did significantly better than males in EFS in the early three studies. The gender difference was not significant in overall survival, partly because >60% of the males survived after the testicular relapse. Randomized studies in the former three protocols revealed that intermediate- or high-dose methotrexate therapy significantly reduced the testicular relapse rate. In the L95-14 study, gender difference disappeared in EFS. Contrary to the results of larger-scale studies, the randomized control study in the L95-14 reconfirmed with updated data that dexamethasone 8 mg/m(2) had no advantage over prednisolone 60 mg/m(2) in the SR and intermediate-risk groups. Prophylactic cranial irradiation was assigned to 100, 80, 44, and 44% of the patients in the studies, respectively. Isolated central nervous system relapse rates decreased to <2% in the last two trials. Secondary brain tumors developed in 12 patients at 8-22 years after cranial irradiation. Improvement of the remission induction rates and the complete omission of irradiation are currently main objectives in our studies.
Tsuchida
M
M
Department of Pediatric Hematology and Oncology, Ibaraki Children's Hospital, Mito, Japan. mtsuchida@ibaraki-kodomo.com
Ohara
A
A
Manabe
A
A
Kumagai
M
M
Shimada
H
H
Kikuchi
A
A
Mori
T
T
Saito
M
M
Akiyama
M
M
Fukushima
T
T
Koike
K
K
Shiobara
M
M
Ogawa
C
C
Kanazawa
T
T
Noguchi
Y
Y
Oota
S
S
Okimoto
Y
Y
Yabe
H
H
Kajiwara
M
M
Tomizawa
D
D
Ko
K
K
Sugita
K
K
Kaneko
T
T
Maeda
M
M
Inukai
T
T
Goto
H
H
Takahashi
H
H
Isoyama
K
K
Hayashi
Y
Y
Hosoya
R
R
Hanada
R
R
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007564:Japan; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D018365:Neoplasm, Residual; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome