Risk factors for early death in children with haemophagocytic lymphohistiocytosis.
OBJECTIVE
Haemophagocytic lymphohistiocytosis (HLH) is a life-threatening disturbance of immunoregulation. HLH comprises primary and acquired forms with different disease severity. A large proportion of deaths occur early into treatment. We investigated association with early death for laboratory and clinical parameters before the start of and 2 weeks into therapy.


METHODS
A total of 232 children from Scandinavia, Germany or Italy, fulfilling diagnostic criteria and/or with familial disease and/or HLH-causing mutations, receiving HLH treatment 1994-2008 were included. The relation between clinical findings and early pre-transplant death was examined using the Cox proportional hazards model, with a 4-month right-truncation of the outcome. Patients were censored at last follow-up or transplant. Statistically significant predictors were adjusted for sex, age and each other.


RESULTS
The following features were significantly associated with adverse outcome: hyperbilirubinaemia (>50 μmol/L; adjusted hazard ratio (aHR) 3.2; 95% confidence interval 1.3-8.1, p = 0.011), hyperferritinaemia (>2000 μg/L; aHR 3.2; 1.2-8.6, p = 0.019), cerebrospinal fluid pleocytosis (>100 × 10(6) /L; aHR 5.1; 1.4-18.5, p = 0.012) at diagnosis, and thrombocytopenia (<40 × 10(9) /L; aHR 3.4; 1.1-10.7, p = 0.033), and hyperferritinaemia (>2000 μg/L; aHR 10.6; 1.2-96.4, p = 0.037) 2 weeks into therapy. Non-improvement of fever, anaemia and/or thrombocytopenia also had adverse impact.


CONCLUSIONS
There seem to be easily available clinical predictors of early mortality in HLH patients, which may help guide treatment decisions.
Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden. helena.trottestam@ki.se
Helena
H
Trottestam
Elisabet
E
Berglöf
AnnaCarin
A
Horne
Erik
E
Onelöv
Karin
K
Beutel
Kai
K
Lehmberg
Elena
E
Sieni
Thomas
T
Silfverberg
Maurizio
M
Aricò
Gritta
G
Janka
Jan-Inge
JI
Henter
D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002648:Child; D016572:Cyclosporine / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D005293:Ferritins / Q000097:blood; D005334:Fever / Q000209:etiology; D006801:Humans; D006932:Hyperbilirubinemia / Q000209:etiology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007964:Leukocytosis / Q000134:cerebrospinal fluid / Q000209:etiology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality*; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D013921:Thrombocytopenia / Q000209:etiology
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D005047:Etoposide; D003907:Dexamethasone; D016572:Cyclosporine; D005293:Ferritins