Image-Guided Therapy May Reduce the Risk of Traumatic or Failed Lumbar Punctures in Children with Acute Lymphoblastic Leukemia,
Authors: Shaikh Furqan , Alexander Sarah , Tole Soumitra , Voicu Laura , Sung Lillian 
Published: October 2019

Abstract
Abstract 3582

Introduction:
Children with acute lymphoblastic leukemia (ALL) undergo diagnostic and therapeutic lumbar punctures (LPs) with the administration of intrathecal chemotherapy as part of their cancer treatment. Difficult LPs may result in trauma (≥ 10 RBCs/μL) or a failed attempt to obtain cerebrospinal fluid (CSF). There can be several negative consequences of a difficult LP. For patients with newly diagnosed ALL, a traumatic lumbar puncture (TLP) that contains blasts obscures the correct determination of CNS status, leads to a requirement for additional therapy, and is associated with a poorer event-free survival. A failed lumbar puncture (FLP) provides inadequate diagnostic material, can be associated with pain, and leads to a delay in administering intrathecal chemotherapy. There is a need to identify interventions that can help reduce difficult lumbar punctures. At the Hospital for Sick Children (SickKids), children with difficult LPs may be referred to undergo the procedure under image-guided therapy (IGT) with fluoroscopy. We hypothesized that the use of IGT may reduce the risk of difficult LPs. The primary objective of this study was to investigate whether the use of IGT could reduce the risk of difficult LPs defined as TLPs and FLPs in children with ALL. The secondary objective was to determine whether IGT could reduce the risk of macroscopically bloody LPs (≥ 500 RBC/μl).

Methods:
The health records of all children less than 18 years of age with newly diagnosed ALL at SickKids from 2005 to 2009 inclusive were retrospectively reviewed. Data was collected on patients referred for at least one IGT procedure. The proportion of difficult LPs with and without IGT were compared. We used univariate and multiple conditional logistic regression (repeated-measures) analysis to examine the association between IGT and difficult LPs. The potential covariates analyzed included age at procedure (younger vs. older than 10 years), body mass index percentile (less vs. more than 95), platelet count (less vs. more than 100 × 109/L), previous TLP (yes vs. no), days since previous LP (less vs. more than 15 days), and phase of treatment (before vs. after the start of maintenance). In order to create multiple regression models, covariates that changed the beta-coefficient of the IGT effect by more than 10% were included in the model.

Results:
Among 267 children diagnosed with ALL in the study period, 25 patients (9.4%) had at least one image-guided LP. Of these 25 patients, 52% were over 10 years old, 64% were female and 28% were obese. These patients had a total of 542 LPs, of which 229 (42%) were performed with image-guidance and 313 were performed using the standard palpation method. Among all LPs, 149 (28%) were traumatic and 19 (4%) were failed. In univariate analysis, the use of IGT significantly lowered the odds of a difficult LP (TLP or FLP), with an odds ratio (OR) of 0.44 (95% confidence interval (CI) 0.26 to 0.76; p=0.003). The other covariates that were significant in univariate analysis included days since previous LP (OR 0.55, 95% CI 0.36 to 0.83; p=0.005) and phase of treatment (OR 0.60, 95%CI 0.39 to 0.91; p=0.017). Multivariable analysis adjusting for days since previous LP and phase of treatment demonstrated that the effect of IGT remained significantly independently associated with a reduction in difficult LPs (OR 0.49, 95% CI 0.29 to 0.86; p=0.012). In a secondary analysis, we defined bloody lumbar punctures (BLP) as ≥ 500 RBCs/μL. The effect of IGT in reducing BLP or FLP was larger, with an OR of 0.11 (95% CI 0.04 to 0.28, p<0.0001).

Conclusions:
This retrospective cohort study suggests that image-guidance may reduce the risk of traumatic and failed LPs in children with ALL. IGT may be more effective in reducing macroscopic trauma. Therefore, IGT may be able to provide a potential intervention for children with ALL anticipated to have difficult lumbar punctures at diagnosis, or found to have difficult subsequent procedures. Future work should focus on the development of better models to identify children at highest risk of difficult LPs and non-radiation based image-guided manoeuvres to facilitate LPs in these children.

Disclosures:
No relevant conflicts of interest to declare.