Abstract

Abstract 1497

Background:

The hemophagocytic syndrome (HPS) is a rare but serious condition with a poor prognosis. The syndrome is characterized by hypercytokinemia, macrophage proliferation, and systemic inflammation. In children, the disorder is most commonly a primary dysregulation of the immune system, however, in adults hemophagocytic syndrome is generally a secondary process that is associated most frequently with viral infections, solid or hematologic malignancies (especially lymphoma), and systemic inflammatory conditions. Diagnostic criteria have been extrapolated from experience in children, and prognostic factors have not been well described. It has not been established whether the adult form of HPS is identical to the secondary form in children, or a distinct clinical entity. Additionally, management focuses on controlling the underlying cause, but it is unclear whether further benefit is derived from immunosuppression; optimal management strategies remain unclear.

Objectives:

To document the clinical, biochemical, and histopathological features associated with HPS in adults. To describe treatments used and document clinical outcomes.

Methods:

We performed a systematic review of all case reports or case series of hemophagocytic syndrome between January 1990 and July 2009. We searched Medline (Ovid), Embase (Ovid), Imbiomed, Artemisa, and Lilacs for cases and case series of hemophagocytic syndrome in adults. We included in our analysis those studies that a) clearly described patient demographics, b) described the underlying diagnosis, c) provided sufficient information on diagnostic criteria, d) met the HLH Study Group diagnostic criteria, e) provided sufficient information on therapeutic approaches, and f) provided follow up and/or survival data. For each included case, we extracted demographic, biochemical, clinical, and therapeutic data. Statistical analysis was done using χ2 or unpaired Student's t tests. Potential predictors of mortality were explored using logistic regression.

Results:

A total of 85 cases met our selection criteria. Characteristics are summarized in the table. Among the 44/85 (51.7%) patients that died, mean survival time was 30 days (Figure). Only age, ALP, and –marginally- underlying etiology were significantly different between groups. Other than age, none of the variables in the multivariate analysis were found to correlate significantly with survival.

Conclusion:

Hemophagocytic syndrome in adults carries a high mortality rate. Age may be a predictor of survival. Prospective collaborative studies on HPS in adults are needed to further define the diagnostic characteristics, prognosis and treatment outcomes.

Table.

Characteristics of Survivors and Non-Survivors of HPS

Survived (N=41)Died (N=44)P Value
Mean Age (years) 41.6 49.8 0.03 
Male gender [N(%)] 18 (43.9%) 23 (52.2%) 0.29 
Underlying etiology [N(%)]   0.05 
Viral-associated 9 (21.9%) 16 (36.3%)  
Lymphoma/leukemia-associated 11 (26.8%) 18 (40.9%)  
Infection-associated 5 (12.2%) 5 (11.4%)  
Inflammatory Disease-associated 8 (19.5%) 3 (6.8%)  
No apparent secondary etiology 8 (19.5%) 2 (4.5%)  
Clinical and biochemical parameters    
Splenomegaly [N(%)] 32 (78.0%) 37 (84.1%) 0.33 
Hemoglobin (g/L) 83.6 84.4 0.88 
PMN (×109/L) 2.4 3.0 0.49 
Platelets (×109/L) 62.7 43.6 0.15 
Triglycerides (mM) 5.6 5.5 0.37 
Fibrinogen (g/L) 2.0 2.0 0.96 
Ferritin (ìg/L) 20978 19439 0.84 
CD25 soluble receptor (U/mL) 17990 13426 0.54 
Creatinine (mM) 212 249 0.76 
AST 385.7 240.9 0.30 
ALT 339.5 153.3 0.14 
ALP 361.5 992.4 0.02 
Total bilirubin (ìM) 99.7 102.1 0.96 
LDH (U/L) 2236 1969 0.65 
ESR (mm/hr) 74 56.7 0.73 
CRP (mg/dL) 6.0 9.8 0.20 
Treatment modalities   0.44 
Steroids 25 (61.0%) 25 (56.8%)  
IVIg 13 (31.7%) 8 (18.2%)  
Immunomodulators 11 (26.8%) 10 (22.7%)  
Vinca alkaloids 3 (7.3%) 5 (11.4%)  
Etoposide 6 (14.6%) 10 (22.7%)  
Chemotherapy 12 (29.2%) 15 (34.1%)  
Plasma exchange 4 (9.8%)  
Splenectomy 2 (4.9%) 1 (2.3%)  
Stem cell transplant 4 (9.8%) 2 (4.5%)  
Survived (N=41)Died (N=44)P Value
Mean Age (years) 41.6 49.8 0.03 
Male gender [N(%)] 18 (43.9%) 23 (52.2%) 0.29 
Underlying etiology [N(%)]   0.05 
Viral-associated 9 (21.9%) 16 (36.3%)  
Lymphoma/leukemia-associated 11 (26.8%) 18 (40.9%)  
Infection-associated 5 (12.2%) 5 (11.4%)  
Inflammatory Disease-associated 8 (19.5%) 3 (6.8%)  
No apparent secondary etiology 8 (19.5%) 2 (4.5%)  
Clinical and biochemical parameters    
Splenomegaly [N(%)] 32 (78.0%) 37 (84.1%) 0.33 
Hemoglobin (g/L) 83.6 84.4 0.88 
PMN (×109/L) 2.4 3.0 0.49 
Platelets (×109/L) 62.7 43.6 0.15 
Triglycerides (mM) 5.6 5.5 0.37 
Fibrinogen (g/L) 2.0 2.0 0.96 
Ferritin (ìg/L) 20978 19439 0.84 
CD25 soluble receptor (U/mL) 17990 13426 0.54 
Creatinine (mM) 212 249 0.76 
AST 385.7 240.9 0.30 
ALT 339.5 153.3 0.14 
ALP 361.5 992.4 0.02 
Total bilirubin (ìM) 99.7 102.1 0.96 
LDH (U/L) 2236 1969 0.65 
ESR (mm/hr) 74 56.7 0.73 
CRP (mg/dL) 6.0 9.8 0.20 
Treatment modalities   0.44 
Steroids 25 (61.0%) 25 (56.8%)  
IVIg 13 (31.7%) 8 (18.2%)  
Immunomodulators 11 (26.8%) 10 (22.7%)  
Vinca alkaloids 3 (7.3%) 5 (11.4%)  
Etoposide 6 (14.6%) 10 (22.7%)  
Chemotherapy 12 (29.2%) 15 (34.1%)  
Plasma exchange 4 (9.8%)  
Splenectomy 2 (4.9%) 1 (2.3%)  
Stem cell transplant 4 (9.8%) 2 (4.5%)  

Figure. Kaplan-Meier plot of survival in adult patient with HPS.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.