Incidence and Risk Factors for CNS Relapse in Adult ALL after Allogeneic Hematopoietic Cell Transplantation

Relapse in the central nervous system (CNS) is a devastating outcome in acute lymphoblastic leukemia (ALL). Allogeneic hematopoietic cell transplantation (HCT) in ALL is reserved for patients with high-risk and/or relapsed/refractory disease. However, there is a paucity of data describing the incidence and factors associated with post-HCT CNS relapse in the modern era. In this multicenter retrospective study of adults with ALL who underwent first HCT between 2011 and 2021 at Stanford Health Care (SHC) or University of Washington/Fred Hutch Cancer Center (UW/FH), we aimed to describe the incidence of post-HCT CNS relapse, factors associated with post-HCT CNS relapse, and the impact of CNS relapse on overall survival (OS). A total of 636 patients were included. The 1- and 3-year cumulative incidences of CNS relapse after HCT were 3% and 6%, respectively. Absence of CNS involvement prior to HCT, pre-HCT MRD negativity, and receipt of TBI-based conditioning were significantly associated with decreased risk of post-HCT CNS relapse. These three characteristics defined a composite low-risk group that was associated with lower risk of post-HCT relapse [HR = 0.31 (95% CI, 0.15-0.68), p = 0.0032]. Post-HCT CNS relapse was significantly associated with shorter overall survival [HR 7.33 (95% CI, 5.12-10.49), p < 0.0001]; worse outcomes were seen with earlier post-HCT CNS relapse. Future studies will be needed to assess if this low-risk group may benefit from de-escalation of CNS-directed interventions during HCT.