Effectiveness of prophylactic intrathecal chemotherapy and risk factors of central nervous system relapse after allogeneic hematopoietic cell transplantation in acute myeloid leukemia

Central nervous system (CNS) relapse in patients with acute myeloid leukemia (AML) is rare, and prophylactic intrathecal chemotherapy is not routinely recommended due to a lack of clinical evidence. Nevertheless, CNS relapse can lead to significant neurological complications and a poor prognosis. Therefore, we aimed to evaluate the effectiveness of prophylactic intrathecal chemotherapy and identify the risk factors associated with CNS relapse in AML patients who underwent hematopoietic cell transplantation (HCT). We conducted a retrospective analysis of data from 960 AML patients who received HCT between 2000 and 2020 at Asan Medical Center (Seoul, Korea). According to our institution's protocol, we administered prophylactic intrathecal infusions of methotrexate (MTX) four times during the pre- and post-HCT periods. Of the 960 patients, twenty-seven developed CNS relapse (2.8%), with a median onset of 6.3 months following HCT. The 5-year CNS relapse rate tended to be lower in the intrathecal MTX group compared to the no intrathecal MTX group (2.7% vs. 7.4%, P = 0.132), albeit without statistical significance. However, the increased number of intrathecal chemotherapy was not correlated with the risk reduction of CNS relapse. Independent significant risk factors for CNS relapse included an initial higher white blood cell count (≥ 40 x10 ³ /µL), extramedullary involvement, French-American-British (FAB) subtypes M3/M4, and poor-risk cytogenetics. In conclusion, our findings suggest that repeated prophylactic intrathecal chemotherapy is not essential for all AML patients undergoing HCT. However, intrathecal chemotherapy may be beneficial for certain patients with high-risk factors.