Incidence, treatment and outcome of central nervous system relapse in adult acute lymphoblastic leukaemia patients treated front-line with paediatric-inspired regimens: A retrospective multicentre Campus ALL study

Abstract

Within the Campus ALL network we analyzed the incidence, characteristics, treatment and outcome of a central nervous system (CNS) relapse in 1035 consecutive adult acute lymphoblastic leukemia (ALL) patients treated frontline with pediatric-inspired protocols between 2009 and 2020. Seventy-one patients (6.8%) experienced a CNS recurrence, more frequently in T- (28/278; 10%) than in B-ALL (43/757; 5.7%) (p = 0.017). An early CNS relapse-< 12 months from diagnosis-was observed in 41 patients. In multivariate analysis, risk factors for early CNS relapse included T-cell phenotype (p = <0.001), hyperleucocytosis >100 × 10⁹ /L (p<0.001) and male gender (p = 0.015). Treatment was heterogeneous, including chemotherapy, radiotherapy, intrathecal therapy and novel agents. A complete remission (CR) was obtained in 39 patients (55%) with no differences among strategies. After CR, 26 patients underwent an allogenic transplant, with a significant overall survival benefit compared to non-transplanted patients (p = 0.012). After a median observation of 8 months from CNS relapse, 23 patients (32%) were alive. In multivariate analysis, the time to CNS relapse was the strongest predictor of a lower 2-year post-relapse survival (p<0.001). In conclusion, in adult ALL the outcome after a CNS relapse remains very poor. Effective CNS prophylaxis remains the best approach and allogenic transplant should be pursued when possible.

Keywords: CNS relapse; adult ALL; paediatric-like regimens.

FIGURE 1

(A) Overall survival (OS) of the whole population (71 cases) from the first central nervous system (CNS) relapse. Median OS was 8.5 months [95% CI:6–14]. (B) OS from CNS relapse by time from initial diagnosis (early <12 months; late ≥12 months). The median OS in early and late CNS relapse was six months (95% CI:3–8) and 14 months (95% CI:8.0–20.0) respectively (p < 0.001). (C) OS from CNS relapse by site of relapse. Median OS after isolated CNS relapse, CNS plus concomitant bone marrow (BM) minimal residual disease (MRD)‐positive relapse and CNS plus concomitant haematologic relapse was 14 (95% CI:8–20), 12.5 (95% CI:1–22) and 5 (95% CI:1–7) months respectively (p = 0.03).