Clinical and Laboratory Evaluation of Patients with Familial Hemophagocytic Lymphohistiocytosis in a Single Center; Striking the Importance of Central Nervous System and Hepatic Involvement

Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive, life-threatening condition characterized by deficient immune response. The major underlying defect in FHL is impaired Natural Killer (NK) cell and T lymphocyte degranulation and/or cytotoxicity, and the only curative treatment is hematopoetic stem cell transplantation (HSCT).

In this retrospective study, 57 patients who were diagnosed with FHL at Hacettepe University Ýhsan Dogramacý Children’s Hospital Pediatric Hematology Department, between November 1994 and December 2012 were evaluated for their clinical and laboratory findings, factors affecting the response to treatment, prognosis and survival.

Median age of these patient’s was 18 months (0.16-226 months). Mutation analysis were performed in 37 patients and of these, 11 had UNC13D, 10 had PRF1 and three had STX11 gene mutation. Fourty four persent of the patients had central nervous system (CNS) involvment on admission and spinal cord involvement was also seen on five patients. The median age of the patients who had spinal cord involvement was 11 years (7.5-14 years) and all of these have neurological symptoms, positive cerebrospinal fluid (CSF) and brain MRI findings related to FHL. One of the patients had spinal cord involvement on admission, the other four patients developed spinal cord involvement at follow up and all of these four patients were died despite HSCT.

Remission was achieved in 24 patients with the treatment protocols, HLH-1994 and HLH-2004, in a median time of 76 days (min-max:15-705 days). When factors affecting the remission time were evaluated, remission time was prolonged 3.1 times in patients with ferritin level ≥1500 mg/dL. The five year overall survival was 25% and HSCT was performed in 18 patients (32%) and five year survival rate was 44% in the transplant group.

When patients were grouped according to their ages [Group 1 (0-24 months) and Group 2 (>24 months)]; there were 33 patients below two years and 24 patients above two years. Patients in Group 1 had higher ferritin (p=0.001) and AST (p=0.043) levels whereas lower fibrinogen (p=0.023) levels on admission, survival rate was also lower in these patients (p=0.017). When we analyze the patients in Group 1, we found that patients with hepatic involment had poor prognosis (p=0.002).

In conclusion, FHL is a disease with high mortality rates and the only curative treatment is HSCT. When FHL is suspected, genetic studies should be done and not only CNS but also spinal cord imaging should be performed as well. Treatment must be started immediately in patients who has poor prognostic factors including, age below two years, ferritin level above 1500 mg/dL, and spinal cord, bone marrow or hepatic involvement.