Case 1: A 25-year-old female (born 1993) presented in 2018 with fatigue, anemia, and pancytopenia. Bone marrow biopsy revealed high blast count with flow cytometry showing CD33 (94%), CD117 (73%), MPO (98%) positivity, and limited CD34 (3-4%) expression. Cytogenetic analysis was negative for t(8;21), inv(16), t(15;17), and BCR-ABL, classifying the case as cytogenetically normal intermediate-risk AML.

Brain MRI revealed meningeal involvement at diagnosis. The patient received standard 7+3 induction (cytarabine + idarubicin) achieving complete hematologic remission. Due to absence of suitable donor, autologous stem cell transplantation was performed. Despite achieving complete remission and remaining asymptomatic, prophylactic intrathecal methotrexate and cytarabine was initiated every 6 months for CNS protection.

Serial CSF examinations from 2019-2024 showed no blast cells. Bone marrow biopsies consistently demonstrated hypocellular marrow without blasts, with negative CD34 and CD117. The patient has maintained complete remission for 7 years without neurological symptoms or complications.

Case 2: A 46-year-old male (born 1973) presented in 2019 with anemia, thrombocytopenia, and fatigue. Bone marrow analysis confirmed AML with flow cytometry showing CD33 (99%), MPO (98%), high HLA-DR expression, but negative CD34 and CD117, consistent with aggressive AML phenotype.

CSF examination at diagnosis confirmed CNS involvement. After achieving complete remission with standard 7+3 induction (cytarabine + daunorubicin), the patient underwent allogeneic stem cell transplantation. Similar to Case 1, prophylactic intrathecal methotrexate and cytarabine was administered every 6 months despite clinical remission.

Follow-up from 2020-2023 showed consistently negative CSF examinations and stable bone marrow remission with <5% blasts. The patient has maintained complete remission for 6 years without transplant complications or neurological sequelae.

Discussion: These cases demonstrate several important clinical principles in managing AML with CNS involvement. First, both patients achieved sustained remission despite CNS involvement at diagnosis, traditionally associated with poor prognosis. The combination of intensive systemic therapy, stem cell transplantation, and prolonged prophylactic intrathecal therapy appears crucial for success.

The extended prophylactic intrathecal therapy regimen (6-7 years) far exceeds standard recommendations but proved remarkably safe and effective. The 6-monthly interval appears optimal, providing adequate CNS protection while minimizing procedure-related risks and patient burden compared to more frequent administration.

The contrasting transplant approaches (autologous vs. allogeneic) achieved similar outcomes, suggesting that the prophylactic intrathecal strategy may be more important than transplant type for CNS disease control. Both patients demonstrated excellent tolerance to repeated lumbar punctures without cumulative neurotoxicity.

The absence of CNS relapse in both cases over 6-7 years strongly supports the efficacy of this prophylactic approach. Traditional concerns about prolonged intrathecal therapy causing neurotoxicity were not observed, possibly due to the extended interval between treatments.

Conclusion: Extended prophylactic intrathecal therapy administered every 6 months following stem cell transplantation represents a safe and highly effective strategy for preventing CNS relapse in AML patients with initial CNS involvement. These cases challenge conventional limitations on prophylactic therapy duration and support consideration of extended prophylaxis in high-risk patients. The excellent long-term outcomes without significant complications suggest this approach should be considered for similar cases, potentially improving survival in this traditionally poor-prognosis population.