Hemophagocytic Lymphohistiocytosis Is Not Only a Childhood Disease: A Multi-Center Study of 613 Cases from Chinese HLH Workgroup

Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome. It occurs as a primary or acquired disorder in a condition of chaotic and uncontrolled immune system stimulation. Recent studies showed that HLH occurs not only in children, but also in adult. Here we presented the data gathered from Chinese HLH Workgroup in order to make further understanding about the disease.

Methods: We performed a multi-center study involving 613 cases of HLH patients. We analyzed the clinical features, laboratory tests, diagnosis, treatments and clinical outcomes of them. All the date came from 46 hospitals, between Jan 2006 to June 2014.

Results: The median age was 29 years old (Range 1 month to 82 years old). Forty-nine cases of them were primary HLH, 489 cases were acquired HLH and the other 75 case had unknown underlying disease. Among the acquired HLH group, 211 cases were malignancy-associated HLH (M-HLH),207 cases were infection- associated HLH (I-HLH), 58 cases were macrophage activation syndrome (MAS), 9 cases were associated with pregnancy, 3 patients developed HLH after autologous hematopoietic stem cell transplantation, and one case was associated with hemolytic anemia. Over ninety percent (93.3%) of the patients had hepatic function damage. We found significant difference in some diagnostic criteria among M-HLH, I-HLH and MAS group. The mean leukocytes was (9.50±8.46)×10⁹/L, and the mean thrombocytes was (100.69±87.61)×10⁹/L , which were significantly higher in MAS group than the other. The brain natriuretic peptide (BNP) was higher in patients with M-HLH (5477.31±6048.08 pg/ml). The aspartate aminotransferase (AST) was and bilirubin were significantly higher in patients with I-HLH. The median survival time of 613 cases is 7 months. Until now, 258 cases of patients were still survived, 297 cases were died, and the other was lost. We observed 45 cases who underwent allogenic hematopoietic stem cell transplantation (allo-HCT), including 22 cases of primary HLH, 12 cases of M-HLH, 8 cases of EBV-HLH and 3cases with unknown underlying disease. In these allo-HCT patients, 26 cases were achieved complete remission (CR), 12 cases died from transplantation related mortality (TRM), and the other died from tumor relapse or refractory EBV infection. The dead exhibited much higher level in bilirubin, lactate dehydrogenase (LDH), creatinine, and urea nitrogen. On the contrary, they had lower leukocytes and thrombocytes counts, and hypoalbuminemia. Thrombocytopenia and hypoalbuminemia play an important role in poor prognosis.

Conclusion: HLH is not only a childhood disease but also occurs in adult. It associated with many underlying conditions. Lymphoma and EBV infection were two major causes of acquired HLH. Hepatic function damage is one of the most typical HLH clinical manifestations, and it tends to be more serious for patients with I-HLH. In addition, the blood cells of the patients with MAS may not reduce in the early phase; and the patients with M-HLH are easy to catch cardiac dysfunction. Acquired HLH is still a high mortality disease, and allo-HCT is one of the effective means of treatment for acquired HLH. Thrombocytopenia and hypoalbuminemia play an important role in poor prognosis.