Faculty Collaboration Database

Severe neurologic side effects in patients being treated for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2009 May;52(5):621-5

Date

01/13/2009

Pubmed ID

19137570

Pubmed Central ID

PMC3660724

DOI

10.1002/pbc.21838

Scopus ID

2-s2.0-63649136333 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

BACKGROUND: Hemophagocytic Lymphohistiocytosis (HLH) is characterized by uncontrolled inflammation that is generally fatal without immune modulating chemotherapy. At Texas Children's Hospital, we have observed significant central nervous system (CNS) toxicity in several patients treated for HLH according to the Histiocyte Society protocol HLH-2004 in which cyclosporine is given early in the treatment regimen.

METHODS: Patients diagnosed with HLH at Texas Children's Hospital between April 2004 and October 2007 were identified and charts were reviewed. A reference group of patients treated between August 2001 and March 2004, prior to the introduction of HLH-2004, was also evaluated.

RESULTS: Five of 17 patients in the study group developed severe neurotoxicity. Four had new onset seizures associated with significant MRI abnormalities, while the fifth died of intracerebral hemorrhage. Timing of the development of neurologic side effects ranged from day 5 to week 6 of therapy. Cyclosporine levels were outside the therapeutic range (200-300 ng/ml) prior to the onset of symptoms in two of the five patients. Systolic blood pressures for all five patients were greater than the 95th percentile for age on at least one measurement within 24 hr of the onset of neurologic symptoms. MRI scans obtained within 24 hr of seizure activity in four patients were consistent with posterior reversible encephalopathy syndrome (PRES). By comparison only one patient in the reference group (n = 15) had neurotoxicity (PRES).

CONCLUSIONS: Patients being treated for HLH appear to be at risk for neurotoxicity, particularly PRES. Elevated blood pressure, worsening renal and liver function, increased cyclosporine levels, and CNS involvement of HLH may be triggers for the neurotoxic side effects of treatment. Patients being treated on HLH-2004 require close monitoring of their neurologic status and modifiable risk factors such as hypertension should managed aggressively. If larger studies validate our observations, it will be important to determine if up-front cyclosporine in HLH protocols confers a survival benefit that outweighs the potential risk of increased neurotoxicity.

Author List

Thompson PA, Allen CE, Horton T, Jones JY, Vinks AA, McClain KL

Author

Test W. User test user title in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Central Nervous System Diseases
Chemical and Drug Induced Liver Injury
Child
Child, Preschool
Cyclosporine
Female
Humans
Infant
Liver Diseases
Lymphohistiocytosis, Hemophagocytic
Magnetic Resonance Imaging
Male
Models, Biological