The utility of performing the initial lumbar puncture on day 8 in remission induction therapy for childhood acute lymphoblastic leukemia: TCCSG L99-15 study

Abstract

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+.

Procedure: 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.