Delay of the diagnostic lumbar puncture and intrathecal chemotherapy in children with acute lymphoblastic leukemia who undergo routine corticosteroid testing: Tokyo Children's Cancer Study Group study L89-12.
OBJECTIVE
To determine the effects of eliminating initial lumbar punctures in 418 consecutively treated children with acute lymphoblastic leukemia (ALL).


METHODS
Patients were enrolled onto a trial conducted in central Japan between 1989 and 1992. Treatment consisted of standard four-drug induction therapy followed by a risk-based intensification phase, reinduction therapy, late intensification, and remission maintenance therapy (total of 104 weeks). The initial lumbar puncture, with an intrathecal injection of chemotherapy, was performed after 1 week of prednisolone sensitivity testing (day 8). End points included response to prednisolone, CNS status at the time of the day 8 lumbar puncture, subsequent adverse events in CNS and bone marrow, and event-free survival (EFS).


RESULTS
The remission induction rate was 93.1% with a 6-year EFS rate (+/- SE) of 68.7% +/- 2.4%, which is similar to historical results for patients who received their diagnostic lumbar puncture and first instillation of intrathecal chemotherapy on day 0. Overall, 84.5% of the patients had good responses to prednisolone, whereas 15.5% had poor responses. Clinical outcome was strikingly better for the good responders (6-year EFS, 74.1% +/- 2.5% compared with 40.1% +/- 6.4% for patients with poor responses), suggesting that omission of intrathecal chemotherapy did not alter the predictive value of drug sensitivity testing. Eighteen patients experienced CNS relapse as their first adverse event (cumulative risk, 5.1%; 95% confidence interval, 2.7% to 7.4%), coincident with reports from groups using conventional strategies of CNS clinical management. Bleeding into the CSF at the time of the day 8 lumbar puncture was apparent in 29 cases (8.1%), but leukemic blasts were identified in only two.


CONCLUSIONS
Delay of the initial lumbar puncture and intrathecal injection of chemotherapy seems to be feasible in children with ALL. Further controlled evaluations are needed to establish the validity of this conclusion.
Manabe
A
A
Tokyo Children's Cancer Study Group, Japan. manabe@ims.u-tokyo.ac.jp
Tsuchida
M
M
Hanada
R
R
Ikuta
K
K
Toyoda
Y
Y
Okimoto
Y
Y
Ishimoto
K
K
Okawa
H
H
Ohara
A
A
Kaneko
T
T
Koike
K
K
Sato
T
T
Sugita
K
K
Bessho
F
F
Hoshi
Y
Y
Maeda
M
M
Kinoshita
A
A
Saito
T
T
Tsunematsu
Y
Y
Nakazawa
S
S
D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007223:Infant; D007278:Injections, Spinal / Q000009:adverse effects; D007564:Japan / Q000453:epidemiology; D015993:Life Tables; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D009364:Neoplasm Recurrence, Local; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D011239:Prednisolone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D012306:Risk; D012680:Sensitivity and Specificity; D013129:Spinal Puncture / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005938:Glucocorticoids; D011239:Prednisolone; D008727:Methotrexate