Korean J Hematol.  2012 Dec;47(4):273-280. 10.5045/kjh.2012.47.4.273.

Central nervous system (CNS) involvement is a critical prognostic factor for hemophagocytic lymphohistiocytosis

• Kim MM
• Yum MS
• Choi HW
• Ko TS
• Im HJ
• Seo JJ
• Koh KN

• KMID: 1832106
• DOI: http://doi.org/10.5045/kjh.2012.47.4.273

Abstract

BACKGROUND
Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem disorder that frequently involves the central nervous system (CNS). We compared the clinical characteristics, treatment, and prognosis of patients with HLH according to the degree of CNS involvement.
METHODS
The clinical manifestations, initial laboratory data, treatment, and outcomes for 50 patients diagnosed with HLH and treated at Asan Medical Center between January 1995 and August 2011 were retrospectively reviewed and analyzed. CNS involvement was defined as the presence of neurological symptoms or an elevated white blood cell (WBC) count in the cerebrospinal fluid (CSF).
RESULTS
Among these 50 patients, 23 (46%) developed CNS disease. Among patients with CNS disease, 19 had neurological symptoms, including seizures, altered consciousness, facial palsy, dysarthria, and dysphagia. Four patients had elevated CSF WBC counts without neurological symptoms. Twelve patients had abnormal brain imaging results, including high signal intensity lesions on T2-weighted magnetic resonance imaging (MRI) findings, ventriculomegaly, hemorrhage, atrophy, and leptomeningeal enhancement. Patients with CNS disease had lower ferritin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels as well as reduced 5-year survival as compared to those without CNS disease.
CONCLUSION
CNS involvement is common among patients with HLH. Overall, patients with CNS disease achieve poorer outcomes than patients without CNS involvement. To improve outcomes, physicians must carefully monitor the neurological manifestations in patients with HLH and administer the appropriate course of intensified chemotherapy to patients with CNS disease.

Keyword

Hemophagocytic lymphohistiocytosis; Central nervous system involvement; Neurological manifestations; Cerebrospinal fluid; Outcome

MeSH Terms

Alanine Transaminase
Aspartate Aminotransferases
Atrophy
Central Nervous System
Central Nervous System Diseases
Consciousness
Deglutition Disorders
Dysarthria
Facial Paralysis
Ferritins
Hemorrhage
Humans
Leukocytes
Lymphohistiocytosis, Hemophagocytic
Magnetic Resonance Imaging
Neuroimaging
Neurologic Manifestations
Organothiophosphorus Compounds
Prognosis
Retrospective Studies
Seizures
Alanine Transaminase
Aspartate Aminotransferases
Ferritins
Organothiophosphorus Compounds

Figure

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  Fig. 1 Cumulative survival rates in the CNS (+) versus CNS (-) groups. The prognosis was worse in the CNS (+) group compared to the CNS (-) group.

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  Fig. 2 (A) Survival according to the chemotherapeutic regimen in all 50 patients. The trend was not statistically significant (P=0.443). (B) Survival according to the chemotherapeutic regimen in the CNS (+) group. The trend was not statistically significant (P=0.215).

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