Primary and Secondary Central Nervous System Involvement in Acute Myeloid Leukemia

Abstract

Introduction: Central Nervous System involvement (CNSi) in patients with Acute Myeloid Leukemia (AML) rarely occurs. It is not well characterized clinically and lacks standardized treatments. Patients and methods: A retrospective analysis of 77 consecutive AML patients with primary and secondary CNSi during 2004-2016 was performed in eight Polish haematological centres. Results: 77 patients (38 with primary CNSi-AML) were included. Median age was 44 years in both groups. Elevated lactate dehydrogenase activity was found in the majority of subjects. Patients in primary CNSi-AML group more often had myelomonocytic and monoblastic AML subtypes (68.4%) compared to secondary CNSi AML (43.5%) (p=0.039). There were no differences between both groups in the number of leukocytes or the proportion of blast cells rates in peripheral blood or bone marrow at AML diagnosis. There were also no statistically significant differences between both groups in the incidence of cytogenetic or molecular abnormalities. In both groups, CNSi was most frequently found in the cerebrospinal fluid and the most common neurological symptom was headache. The following manifestations were more frequent in secondary than in primary CNSi-AML: lower extremity weakness (38.46% vs. 13.16%; p=0.023), paraesthesia (38.46% vs. 13.16%; p=0.023), motor deficits (31.58% vs. 10.53%; p=0.047), and asymmetry of reflexes (26.32% vs. 2.7%; p=0.007). Median pleocytosis was also significantly higher in secondary than in primary CNSi-AML: 27 (IQR 2-146) vs. 2 (IQR: 1-12; p=0.004). Both groups had rather short Overall Survival (OS), with a median of 16.6 months (9.9-NA) for patients with primary CNSi-AML and 15.4 months (10.1-21.1) for patients with secondary CNSi. Conclusion: Patients with CNSi AML were relatively young, having high lactate dehydrogenase activity and high rates of the myelomonocytic and monoblastic/monocytic AML subtypes. The advisability of undertaking CNS examination and prophylaxis in patients with such characteristics thus merits further reassessment.

A narrative review of central nervous system involvement in acute leukemias

“…It can be present at the initial diagnosis, but also can develop at any time during the natural course of disease, even after years of complete remission, as isolated CNS relapse (38). There is great variability in the incidence of CNS involvement between various forms of acute leukemia, but in recent years the trend has continuously increase thus stimulating a more in-depth analysis over this kind of extramedullary disease (EMD).…”

Clinical Reasoning: A 59-Year-Old Woman Presenting With Diplopia, Dysarthria, Right-Sided Weakness, and Encephalopathy

“…This may manifest as headache, altered consciousness, cranial nerve palsies, intracranial hemorrhage, visual changes, and spinal cord compression. 4 However, our patient's cytology was negative on 2 repeat lumbar punctures despite rapid deterioration, thus making disease progression a less likely etiology. MTX, regardless of administration route, portends a risk of systemic and neurologic toxicities.…”

Acute monocytic leukemia presenting as generalized lymphadenopathy and skin rash in a toddler: highlighting the clinicopathologic mimics

“…Younger age has been reported to be associated with more frequent occurrence of extramedullary and CNS involvement at diagnosis, as was apparent in the index case. The CNS involvement in adults with AML is much rarer 1,4,6 . The higher incidence of CNS involvement in children may probably be attributed to the greater vasculature of their leptomeninges and to the higher prevalence of monoblastic leukemia in infants, since the monoblasts are believed to retain the ability to migrate into peripheral tissues and to reach the brain via the endothelial cell cytoplasm 14 .…”

“…The incidence of AML increases with age, with a median of 68 years. AML can rarely involve areas other than the bone marrow, at the initial presentation, the most common sites being soft tissue, lymphatic tissues and skin 1 . The incidence of myeloid sarcoma is 2.5% to 9.1% of the patients with AML 2 .…”