The utility of performing the initial lumbar puncture on day 8 in remission induction therapy for childhood acute lymphoblastic leukemia: TCCSG L99-15 study.
BACKGROUND
Traumatic lumbar puncture with leukemic blasts (TLP+), which has been reported to occur 5-10%, in the previous studies, adversely affects the outcome of children with acute lymphoblastic leukemia (ALL). Based on the results from our previous study, we deferred the initial lumbar puncture until day 8 in remission induction therapy in order to reduce the frequency of cases with TLP+.


METHODS
The study was conducted as a prospective cohort study within the Tokyo Children's Cancer Study Group (TCCSG) L99-15 study. Between April 1999 and June 2003, 754 children with newly diagnosed ALL enrolled. The patients received the initial intrathecal chemotherapy after 7 days of prednisolone treatment. The incidence of central nervous system (CNS)-positive (the presence of leukemic blasts in cerebrospinal fluid or cranial nerve palsy) including TLP+ cases and cumulative incidence of CNS relapse were examined.


RESULTS
The incidence of CNS-positive and TLP+ was 2.9% (n = 22) and 0.8% (n = 6), respectively. These incidences were much lower than those in the representative study groups employing the initial IT on day 1. Of 22 patients with CNS-positive, only one patient relapsed in CNS, whereas 22 of the remaining CNS-negative 723 patients suffered from CNS relapse. Overall, event-free survival at 4 year was 78.2 ± 1.6%. Four-year cumulative incidence of any CNS relapse was 3.3 ± 0.7%, which improved from our previous study in spite of limiting the use of cranial irradiation.


CONCLUSIONS
Our strategy reduced the frequency of CNS-positive patients who required reinforcement of CNS-directed therapy without compromising overall outcome.
Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan. hase-dai@umin.net
Daisuke
D
Hasegawa
Atsushi
A
Manabe
Akira
A
Ohara
Akira
A
Kikuchi
Katsuyoshi
K
Koh
Nobutaka
N
Kiyokawa
Takashi
T
Fukushima
Yasushi
Y
Ishida
Tomohiro
T
Saito
Ryoji
R
Hanada
Masahiro
M
Tsuchida
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016022:Case-Control Studies; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D007278:Injections, Spinal; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy*; D009426:Netherlands; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy*; D011239:Prednisolone / Q000008:administration & dosage; D011446:Prospective Studies; D012074:Remission Induction; D013129:Spinal Puncture / Q000009:adverse effects / Q000706:statistics & numerical data*; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
D003561:Cytarabine; D011239:Prednisolone; D008727:Methotrexate