Low natural killer activity and central nervous system disease as a high-risk prognostic indicator in young patients with hemophagocytic lymphohistiocytosis.
BACKGROUND
Familial hemophagocytic lymphohistiocytosis HLH (FHL) is fatal, unless patients are rescued with hematopoietic stem cell transplantation (SCT). Although the molecular identification of FHL now is possible at least in part from perforin gene study, many cases escape detection or never are tested due to the lack of specific hallmarks, making diagnosis difficult. To the authors' knowledge, it remains to be determined whether persistently low natural killer cell (NK) activity and a high incidence of central nervous system (CNS) disease increase the probability of FHL.


METHODS
The authors analyzed 42 HLH patients age < 2 years, 13 of whom developed overt CNS disease and 5 of whom demonstrated persistently deficient NK activity (Group 1). The remaining 24 patients had no CNS disease and had NK activity of moderate decrease to within the normal range (Group 2).


RESULTS
In Group 1, CNS symptoms were detected in 6 cases within 1 month and between 4.5-9 months in 6 other patients. In these cases, spotty lesions demonstrating a high T2 signal in the white matter were noted on brain magnetic resonance imaging. The survival was significantly poor for patients in Group 1 unless they were rescued with SCT, which was performed in 5 of the 13 patients with CNS disease and in all 5 patients with persistent NK activity deficiency. SCT was successful in 9 patients, with no CNS sequelae reported after the transplantation. Conversely, the prognosis of the 24 patients in Group 2 was better and only 1 patient required SCT.


CONCLUSIONS
Very young HLH patients (age < 2 years) who are at high risk of fatal FHL with persistently deficient NK activity and/or overt CNS disease require appropriate SCT to reverse CNS disease and achieve a complete cure.
Imashuku
Shinsaku
S
Kyoto City Institute of Health and Environmental Sciences, Kyoto, Japan. shinim95@mbox.kyoto-inet.or.jp
Hyakuna
Nobuyuki
N
Funabiki
Tetsunori
T
Ikuta
Koichiro
K
Sako
Masahiro
M
Iwai
Asayuki
A
Fukushima
Takashi
T
Kataoka
Satoshi
S
Yabe
Miharu
M
Muramatsu
Kazuhiro
K
Kohdera
Urara
U
Nakadate
Hisaya
H
Kitazawa
Katsuhiko
K
Toyoda
Yasunori
Y
Ishii
Eiichi
E
D017668:Age of Onset; D001921:Brain / Q000000981:diagnostic imaging; D001927:Brain Diseases / Q000150:complications / Q000175:diagnosis* / Q000276:immunology; D002675:Child, Preschool; D003937:Diagnosis, Differential; D004358:Drug Therapy; D020031:Epstein-Barr Virus Infections / Q000150:complications; D005260:Female; D015616:Histiocytosis, Non-Langerhans-Cell / Q000175:diagnosis* / Q000209:etiology / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D007223:Infant; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D011379:Prognosis; D011859:Radiography; D012307:Risk Factors