Clinical Outcomes of Acute Myeloid Leukemia Patients with Central Nervous System Disease: A Single Center Retrospective Study

Introduction:
Central nervous system (CNS) involvement is a rare event in acute myeloid leukemia (AML). The exact incidence of CNS disease in AML is unknown as routine diagnostic lumbar puncture is not performed. Also, there is scarce data on the outcomes of AML patients with CNS disease. We analyzed the outcomes of patients of AML patients with CNS disease treated at our institution.
Methods:
We performed a single center retrospective study to investigate the clinical outcomes of adult AML patients with CNS involvement either at the time of initial diagnosis or at relapse.
Results:
Among 124 patients ([AML=94, Acute promyelocytic leukemia (APL)=30], we identified 7 (5.6%) cases with CNS disease; 2 (1.6%) had CNS disease at diagnosis and 5 presented with CNS disease at relapse. The diagnosis of CNS disease was confirmed by magnetic resonance imaging ( MRI), cerebrospinal fluid (CSF) cytology and flow cytometry. Subject races included: Whites (n=‚Äâ4), African Americans (n=2) and Hispanic (n=1). Among the 6 patients with AML, 4 had favorable risk, 1 each had intermediate and adverse risk disease per European Leukemia Network (ELN) classification. The median white blood cell count at diagnosis was 20K/mL. The two patients with CNS disease at diagnosis had headache and other neurological symptoms on presentation. Both patients received induction chemotherapy with fludarabine, idarubicin, cytarabine (FIA) and remain in complete remission (CR) at a mean follow of 7 months. 4 patients (2 with favorable risk, 1 each with intermediate and adverse risk) developed CNS disease at relapse. The cytogenetic and molecular profile of patients who developed CNS disease at relapse are as follows: 2 with core binding factor AML [1 each with t (8,21) and inversion 16], 1 patient with FLT3 and NPM1 mutation and 1 patient with chronic myeloid leukemia with myeloid blast crisis. The median time from AML diagnosis to CNS relapse was 15 months. All 4 patients with CNS disease at relapse died and the median overall survival (OS) from CNS relapse was 5.5 months. 1 patient with APL presented with intracranial myeloid sarcoma 96 months after initial diagnosis and was reinduced with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) achieving a CR; however, patient died 30 months after CNS relapse.
Discussion:
CNS involvement in patients with AML is rare. Patients with CNS disease at relapse tend to have a poor overall survival. Future studies are required to provide a risk adapted AML therapy to mitigate the risk of CNS relapse.