How to Treat Involvement of the Central Nervous System in Hemophagocytic Lymphohistiocytosis?
Central nervous system (CNS)-hemophagocytic lymphohistiocytosis (HLH) is not a disease in itself, but it is part of a systemic immune response. The vast majority of patients with CNS-HLH also have systemic HLH and a large number of patients with primary and secondary HLH have CNS involvement. Reactivations within the CNS are frequent during the course of HLH treatment and may occur concomitant with or independent of systemic relapses. It is also important to consider primary HLH as an underlying cause of "unknown CNS inflammation" as these patients may present with only CNS disease. To initiate proper treatment, a correct diagnosis must be made. A careful review of the patient's history and a thorough neurological examination are essential. In addition to the blood tests required to make a diagnosis of HLH, a lumbar puncture with cerebrospinal fluid (CSF) analysis and magnetic resonance imaging (MRI) should always be done in all cases regardless of the presence or absence of neurological signs or symptom. Treatment options for CNS-HLH include, but are not limited to, those commonly used in systemic HLH, including corticosteroids, etoposide, cyclosporine A, alemtuzumab, and ATG. In addition, intrathecal treatment with methotrexate and corticosteroids has become a standard care and is likely to be beneficial. Therapy must be initiated without inappropriate delay to prevent late effects in HLH. An interesting novel approach is an anti-IFN-gamma antibody (NI-0501), which is currently being tested. Hematopoietic stem cell transplantation (HSCT) also represents an important CNS-HLH treatment; patients with primary HLH may benefit from immediate HSCT even if there is active disease at time of transplantation, though care should be taken to monitor CNS inflammation through HSCT and treat if needed. Since CNS-HLH is a condition leading to the most severe late effects of HLH, early expert consultation is recommended.
Department of Women's and Children's Health, Karolinska Institute, Division of Pediatrics Karolinska University Hospital, Stockholm, Sweden. annacarin.horne@karolinska.se.
AnnaCarin
A
Horne
Department of Women's and Children's Health, Karolinska Institute, Division of Pediatrics Karolinska University Hospital, Stockholm, Sweden.
Ronny
R
Wickström
Department of Pediatrics, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Michael B
MB
Jordan
Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
E Ann
EA
Yeh
Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Ahmed
A
Naqvi
Department of Women's and Children's Health, Karolinska Institute, Division of Pediatrics Karolinska University Hospital, Stockholm, Sweden.
Jan-Inge
JI
Henter
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
Gritta
G
Janka
Central nervous system (CNS); Cerebrospinal fluid; Hemophagocytic lymphohistiocytosis (HLH); Intrathecal treatment; Long-term effects; Neuroradiology; Overall survival; Treatment