CENTRAL nervous system relapse remains an important clinical challenge in adults with acute lymphoblastic leukaemia after allogeneic haematopoietic cell transplantation, with new findings identifying key disease characteristics associated with increased risk.
CNS Relapse After Transplant in Acute Lymphoblastic Leukaemia
Researchers conducted a retrospective analysis of 748 adult patients with acute lymphoblastic leukaemia who underwent allogeneic haematopoietic cell transplantation between 2009 and 2022. All individuals had previously received a modified hyper CVAD chemotherapy regimen that included six planned doses of intrathecal chemoprophylaxis.
Most patients in the cohort underwent conditioning with total body irradiation before transplantation. Despite these preventative strategies, central nervous system relapse was documented in 38 patients, representing 5.1% of the study population.
The median time to central nervous system relapse following transplantation was 10.6 months. Although relatively uncommon, this pattern of recurrence remains clinically significant because of its implications for long term disease control and survival.
Risk Factors Associated with CNS Relapse
Analysis of patient characteristics identified several factors linked to a higher risk of central nervous system relapse. The majority of cases occurred among individuals with Philadelphia chromosome positive acute lymphoblastic leukaemia.
Specifically, central nervous system relapse occurred significantly more frequently in patients with Philadelphia chromosome positive disease compared with those with Philadelphia chromosome negative disease (9.7% versus 1.4%; p<0.001). Hyperleukocytosis at diagnosis was also associated with increased risk (8.1% versus 2.5%; p<0.001).
Additional findings suggested that disease status before transplantation may influence relapse risk. In patients with Philadelphia chromosome positive acute lymphoblastic leukaemia, negative measurable residual disease before transplantation was associated with a lower likelihood of central nervous system relapse.
Preventive strategies appeared to influence outcomes differently depending on disease subtype. Prophylactic intrathecal therapy and total body irradiation-based conditioning were associated with a reduced risk of central nervous system relapse in patients with Philadelphia chromosome negative disease.
Survival Outcomes Following CNS Relapse
The study also examined survival outcomes following relapse. Five-year overall survival differed substantially depending on the relapse pattern. Patients with central nervous system relapse demonstrated a five-year overall survival of 30.4%, compared with 7.6% for other relapse types.
Isolated central nervous system relapse was associated with the most favourable outcomes within the cohort.
Overall, the findings suggest that Philadelphia chromosome positive acute lymphoblastic leukaemia with poor molecular response and high tumour burden at diagnosis may represent a distinct high-risk subgroup for central nervous system relapse. The authors indicated that these results highlight the need for novel central nervous system directed prevention strategies to improve outcomes after transplantation.
Reference
Lee JH et al. Relapse patterns focusing on central nervous system involvement after allogeneic hematopoietic cell transplantation in adult patients with acute lymphoblastic leukemia. Bone Marrow Transplantation. 2026; https://doi.org/10.1038/s41409-026-02807-2.
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