Heterogeneity in the Global Practice of Central Nervous System Staging in Pediatric Acute Lymphoblastic Leukemia

BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) is assessed by cell counting and cytomorphology from cerebrospinal fluid (CSF) and is used for treatment stratification worldwide. The ratio of "CNS2" patients in clinical trials ranges from 3% to 40%, with unclear prognostic significance. PROCEDURE: To assess real-world practice, a survey was distributed globally. Questions focused on the systemic treatment allowed before the staging lumbar puncture, sample handling, methodological details of different analytics, and staging definitions. RESULTS: Eighty-two centers from 47 countries from 5 continents responded. Contraindications and timing of sampling and applied CSF test modalities are heterogeneous. CSF volumes used for cytospins and flow cytometry range widely (15-3000 and 200-4000 µL, respectively). Test positivity definitions vary between ≥1 and ≥5 identified blasts for cytospin and ≥1 to ≥50 blasts for flow cytometry. Differences in practice were seen between countries in the same ALL consortium and within individual countries. CONCLUSIONS: The observed heterogeneity impacts CNS staging and treatment decisions worldwide. Our results may explain the conflicting published evidence on the prognostic value of minimal leukemic CNS involvement. A global consensus on CNS diagnostics and a more detailed reporting of CNS staging methods in clinical studies are urgently needed.