Central nervous system involvement and relapse in adult acute lymphoblastic leukaemia—a population‐based analysis in 2007–2022

Summary Central nervous system (CNS) involvement and relapse remains a clinical challenge in the management of acute lymphoblastic leukaemia (ALL), and studies among adult ALL patients are scarce. We identified all adult ALL patients in Sweden between 2007 and 2022 ( n = 838) from the population‐based ALL register and evaluated factors associated with CNS involvement and relapse. CNS involvement at diagnosis was detected in 7.8% of patients, more often in patients with T‐cell ALL (T‐ALL) and with white blood cell (WBC) count >30 × 10 9 /L, without affecting overall survival or risk of any relapse. The 5‐year cumulative incidence of CNS relapse was 4.6% (95% confidence interval CI 3.1–6.6), with WBC count >100 × 10 9 /L and male sex as independent risk factors. Furthermore, CNS involvement at diagnosis increased the rate of CNS relapse in B‐cell ALL (B‐ALL) (hazard ratio HR 4.52, 95% CI 1.35–15.2), but not T‐ALL (HR 0.94, 95% CI 0.12–7.53). Neither Philadelphia chromosome status nor KMT2A::AFF1 was associated with CNS involvement at diagnosis or CNS relapse. Patients with CNS relapse had a 2‐year overall survival of 34% (13% if relapse occurred <12 months from diagnosis). We conclude that contemporary treatment protocols can prevent CNS relapse for most patients but suggest that B‐ALL patients with CNS involvement may have an unmet need for improved CNS‐directed therapy.