Frequency and spectrum of central nervous system involvement in 193 children with haemophagocytic lymphohistiocytosis.
Haemophagocytic lymphohistiocytosis (HLH) may cause meningoencephalitis and significant neurological sequelae. We examined the relationship between neurological symptoms and cerebrospinal fluid (CSF) at diagnosis, and long-term outcome, in all children enroled in the HLH-94-study prior to July 1, 2003, for whom information on CSF at diagnosis was available (n = 193). Patients were divided into four groups: (i) normal CSF (cells/protein) and no neurological symptoms (n = 71); (ii) normal CSF but neurological symptoms (n = 21); (iii) abnormal CSF but no symptoms (n = 50); and (iv) abnormal CSF with neurological symptoms (n = 51). At diagnosis, neurological symptoms were reported in 72/193 (37%) (seizures = 23); abnormal CSF in 101/193 (52%), and either or both in 122/193 (63%). Altogether 16/107 (15%) survivors had neurological sequelae at follow-up (median 5.3 years). Multivariate hazard ratios (HR) for mortality were 0.98 [95% confidence interval (CI) = 0.42-2.31], 1.52 (0.82-2.82) and 2.05 (1.13-3.72) for groups 2-4, compared with group 1. Moreover, sequelae were more frequent in group 4 (7/21, 33%) compared to groups 1-3 (9/86, 10%) (P = 0.015). Patients with abnormal CSF at diagnosis had significantly increased mortality [HR = 1.78 (95% CI = 1.08-2.92), P = 0.023]. Thus, a substantial proportion of HLH survivors suffer neurological sequelae, and children with abnormal CSF have increased risk of mortality and neurological sequelae. Prompt treatment of HLH at onset or relapse may reduce these complications.
Horne
AnnaCarin
A
Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. annacarin.horne@karolinska.se
Trottestam
Helena
H
Aricò
Maurizio
M
Egeler
R Maarten
RM
Filipovich
Alexandra H
AH
Gadner
Helmut
H
Imashuku
Shinsaku
S
Ladisch
Stephan
S
Webb
David
D
Janka
Gritta
G
Henter
Jan-Inge
JI
D000970:Antineoplastic Agents / Q000627:therapeutic use; D002490:Central Nervous System / Q000000981:diagnostic imaging / Q000473:pathology; D002493:Central Nervous System Diseases / Q000134:cerebrospinal fluid / Q000150:complications* / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D015331:Cohort Studies; D003907:Dexamethasone / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D051359:Lymphohistiocytosis, Hemophagocytic / Q000134:cerebrospinal fluid / Q000150:complications* / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012640:Seizures / Q000134:cerebrospinal fluid / Q000150:complications / Q000188:drug therapy; D033581:Stem Cell Transplantation; D015996:Survival Rate; D014057:Tomography, X-Ray Computed
D000970:Antineoplastic Agents; D005047:Etoposide; D003907:Dexamethasone; D008727:Methotrexate