CNS relapse risk and outcomes after allo-HSCT in adults with ALL

Results from a retrospective analysis, evaluating risk and outcomes of central nervous system (CNS) relapse in 748 adult patients with acute lymphoblastic leukemia (ALL) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), were published in Bone Marrow Transplantation by Lee et al. The aim of this analysis was to assess incidence, risk factors, and outcomes of central nervous system (CNS) relapse, to identify characteristics associated with CNS relapse, and to evaluate outcomes with different prophylactic and therapeutic interventions. 

Key data: CNS relapse was associated with Philadelphia chromosome (Ph)-positive vs Ph-negative ALL (9.5% vs 1.2%; p < 0.001) and high vs normal white blood cell (WBC) counts at diagnosis (8.1% vs 2.5%; p < 0.001). Median overall survival (OS) was longer in patients with CNS relapse vs relapse without CNS involvement (15.5 vs 8.6 months; p = 0.008). In Ph‑positive ALL with isolated CNS relapse, ponatinib-based therapy demonstrated a higher 5‑year OS rate vs dasatinib-based therapy (83.3% vs 21.2%; p = 0.011). Poor molecular response (PMR) pre‑allo‑HSCT (p < 0.001) and prophylactic radiation therapy (RT), used when intrathecal chemotherapy was not feasible (p < 0.001), were associated with higher incidence of CNS relapses in Ph‑positive and Ph‑negative ALL, respectively. Conversely, negative measurable residual disease (MRD) pre-transplant in Ph‑positive ALL and total body irradiation (TBI)‑based conditioning in Ph‑negative ALL were associated with reduced CNS relapse risk. 

Key learning: Ph-positive ALL and high WBC are significant risk factors for CNS relapse following allo-HSCT, with PMR further increasing risk in Ph‑positive ALL. The data confirm the importance of CNS-penetrating tyrosine kinase inhibitors (TKIs) in salvage therapy for long-term disease control post‑allo‑HSCT CNS relapse, particularly in Ph‑positive ALL.