Central Nervous System Involvement in Childhood Acute Lymphoblastic Leukemia: An Analysis of Day-One Versus Day-Eight Lumbar Punctures in Remission Induction Therapy.

Abstract

IntroductionTraumatic lumbar puncture (TLP+) can lead to the iatrogenic infiltration of the central nervous system (CNS) by circulating leukemic blast cells in childhood acute lymphoblastic leukemia (ALL). The risk of TLP+ is increased by a number of factors at the time of presentation of the disease, such as a high white cell count (WCC), T-ALL phenotype, and unstable clinical condition of the patient. For this reason, the first lumbar puncture (LP) was deferred until Day Eight of prednisolone prophase during remission induction therapy in one set of patients. The objective was to compare the historical cohort of Day-One LP with Day-Eight LP with respect to the incidence of TLP+ and de novo CNS leukemia.MethodsA retrospective comparative data analysis of 1,185 childhood ALL patients aged 1-16 years was conducted based on the electronic medical records of the pediatric hematology-oncology department of The Indus Hospital (TIH), Karachi, from January 2010 to August 2018. A total of 600 patients whose LP was done on Day One (January 2010-May 2015) were placed in cohort A, whereas 585 patients whose LP was performed on Day Eight (June 2015-August 2018) were placed in cohort B. After the examination of the cerebrospinal fluid (CSF), the status of CNS infiltration was classified as CNS-1, CNS-2, CNS-3, and TLP+.ResultsA total of 1,185 patients were included in the study, of whom 600 patients were in cohort A and 585 patients in cohort B. The incidence of TLP+ was found to be lower in cohort B (1.7%) as compared with the incidence in cohort A (4.3%) (p-value=0.009). However, there was an increase in the incidence of CNS-3 cases in cohort B (8%) as compared to cohort A (3%) (p-value: <0.001). When the CNS status of both the cohorts was compared with that of the internationally published data, a low incidence of TLP+ cases was noted in patients with LP on Day Eight.ConclusionThe modified approach of performing the first LP on Day Eight significantly reduced the incidence of TLP+ cases. However, an unusual finding of a significant increase in the CNS-3 leukemia was noted. More prospective studies are needed to investigate this significant increase in CNS-3 cases.