Clinical analysis of central nervous system leukemia in patients with Acute Myeloid Leukemia

Abstract Background: Central nervous system leukemia (CNSL) represents a rare but severe complication of acute myeloid leukemia (AML), typically conferring poor prognosis. Risk factors and the impact of prophylactic intrathecal (IT) chemotherapy on CNSL development remain inadequately characterized. Aims: To analyze clinical characteristics of AML patients developing CNSL and evaluate the potential effect of prophylactic IT chemotherapy on CNSL incidence and clinical outcomes. Methods: We retrospectively analyzed 54 AML patients diagnosed with CNSL at the Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine (January 2020–February 2025). Clinical parameters, molecular profiles (gene mutations, chromosomal abnormalities), prophylactic IT strategies, and treatment approaches were assessed for their association with CNSL development and prognosis. Results: The cohort comprised 32 males and 22 females with median age 48 years (range: 14–75). Median time from AML diagnosis to CNSL onset was 193 days (range: 95–406). At diagnosis, 14 patients had white blood cell counts ≥100 × 10⁹/L, with a median count of 65.1 × 10⁹/L (range 0.91–269). AML subtypes were predominantly AML-M5 and AML-M2. Next-generation sequencing showed the most common gene mutation was FLT3 (21 patients; FLT3-ITD: 10, FLT3-TKD: 4), followed by CEBPA (12), NRAS (10), and NPM1 (9). Fusion genes included CBFβ-MYH11 (10 patients) and MLL rearrangements (8), consistent with prior reports. Chromosomal abnormalities frequently involved chromosomes 8 and 11. One patient had CNSL at AML diagnosis and was excluded from the prophylactic analysis. The remaining 53 patients were divided into a prophylactic group (≥2 lumbar punctures with IT therapy) and a control group (2 IT treatments). The prophylactic group had a significantly longer median time to CNSL onset compared to the control group (446 ± 324 vs 220 ± 218 days, p0.05), particularly in AML-M5 and AML-M2 subtypes (p0.05). In patients with CBFβ-MYH11 fusion or NRAS mutations, CNSL onset was delayed in the prophylactic group, though without statistical significance. Among the 53 patients, data was missing in 6 cases. Among the remaining 47 patients, 9 cases (19.15%) had bone marrow relapse and CNSL relapse, and 32 cases (68.09%) had simple CNSL relapse. There was no statistical significance between the two groups. Among the 53 patients, follow-up data was not avaiable in16 case. Analysis of the remaining 37 patients showed that 14 cases (37.84%) died and 23 cases (62.16%) survived. There was no statistically significant difference in the overall survival rate between the two groups. Prior Venetoclax/Cytarabine Exposure in non-prophylaxis patients showed no association with CNSL timing (p 0.05) Conclusion: Prophylactic IT chemotherapy (≥2 administrations) significantly delayed CNSL onset in AML patients, particularly in M2/M5 subtypes. However, it did not influence relapse patterns or overall survival. These findings warrant validation in larger prospective cohorts.