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Prognostic factors in secondary adult HLH
factor for poor overall survival; age >45 years and low platelet counts (<35x109/L) were also significant predictive factors for poor overall survival. When we excluded treat- ment response as a parameter, age >45 years, EBV-associ- ation, thrombocytopenia (platelets <35x109/L), and hyper- ferritinemia (>20,000 ng/mL) were associated with poor overall survival. All of these factors were also associated with higher cumulative incidences of progression and poor 8-week response (data not shown). We ultimately selected four factors and weighted them based on the haz- ard ratio: age >45 years (2 points), EBV-association (1 point), low platelet count (<35x109/L) (1 point), and hyper- ferritinemia (>20,000 ng/mL) (1 point). Using these vari- ables, we performed risk scoring and stratification. The 5- year overall survival rates of low-risk (score 0-1), interme- diate-risk (score 2), and poor-risk (score ≥3) patients were 92.1%, 36.8%, and 18.0%, respectively, while the corre- sponding 5-year cumulative incidences of progression were 18.5%, 59.4% and 87.0% (both P<0.001) (Figure 4A,B). In the EBV-HLH subgroup, the 5-year overall sur- vival rate was 59.2% in early stable responders, 44.4% in the late responders, and 0.0% in non-responders.
AB
Multivariate analysis in the EBV-HLH subgroup revealed that maximal EBV RQ-PCR level greater than 5-log, age >45 years, and hyperbilirubinemia were associated with poor overall survival
Discussion
Causes of HLH and the proportions of each identified in the current study differed from those of previous studies, in which the most common cause of secondary HLH was a hematologic malignancy.3,7,8,25 Some patients with malig- nancy-associated HLH die early from rapid deterioration without a suspicion of HLH and their prognosis depends on the outcome of the malignant disease. In the current study we, therefore, analyzed treatment response and prognostic factors for adult secondary HLH after exclud- ing those with malignancy-associated HLH. To the best of our knowledge, this is the largest data set used to analyze prognostic factors in adult patients with secondary HLH without malignancies.
Excluding malignancies, EBV was the most common
CD
Figure 3. Survival outcomes according to treatment response. (A, B) Five-year overall survival according to treatment response at (A) 4 weeks and (B) 8 weeks. (C,D). Five-year (C) overall survival and (D) cumulative incidence progression according to dynamic treatment response at 8 weeks. OS: overall survival; CIP: cumulative incidence of progression.
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