Initial Cerebrospinal Fluid Blast Clearance Rate in Pediatric B-Lymphoblastic Leukemia is Associated With Overall...

Children with central nervous system (CNS) involvement by B-lymphoblastic leukemia (B-ALL) at diagnosis have higher risk features and greater rates of relapse than those without CNS involvement. This study sought to elucidate the relationship between cerebrospinal fluid (CSF) blast clearance rate with overall survival (OS) and relapse in pediatric B-ALL. Patients with CNS involvement of newly diagnosed B-ALL were stratified into 3 CSF clearance groups by days after initial lumbar puncture: fast (1 to 7 d), intermediate (8 to 15 d), and slow (15+ d) clearers. Among 246 new patients, 28% (69) were CSF+ at diagnosis (87% [60] CNS2, 13% [9] CNS3); 55% (38) fast, 35% (24) intermediate, and 10% (7) slow clearers. The hazard ratio for OS was 5.8 (95% CI: 1.2- 27.9, P =0.029) times higher in slow clearers compared with fast clearers, and 17.4 times higher compared with intermediate clearers (95% CI: 1.7-178, P =0.016). There were no significant differences in risk group ( P =0.3) or relapse rates ( P =0.5). These data suggest that among pediatric patients with CNS+ B-ALL disease at diagnosis, those who cleared CSF faster had better OS compared with patients who were slower at clearing the CSF of blasts. A study of the functional dynamics of underlying differences in CSF clearance rates may inform therapeutic modification.