Hemophagocytic Lymphohistiocytosis Secondary to Malignancy and Chemotherapy in Pediatric Patients

Background: Hemophagocytic lymphohistiocytosis (HLH) is an uncommon yet potentially devastating systemic disease arising from uncontrolled activation of the immune system. While the primary form of this disease can be caused by genetic mutation(s), the secondary form maybe triggered by infection, hematologic, malignant and metabolic conditions. Here, we present 3 cases of HLH secondary to malignancy and chemotherapy in pediatric patients. Purpose: The diagnosis of HLH remains a clinical challenge due to nonspecific symptoms such as fever, skin rash, cytopenias and splenomegaly found at presentation. Proper diagnosis is significantly more difficult among patients with acute leukemia who have received chemotherapy and present with fever and pancytopenia. The objective of this study is to describe three unique cases of secondary HLH, describe the specific treatment for this entity, and improve the awareness of this condition Methods: Three patients were diagnosed with HLH at Cook Children’s Medical Center (CCMC) between June 2006 and June 2016. They were treated per HLH-2004 guidelines. Medical records of these patients were reviewed at CCMC. Data collected included timeline of diagnosis of HLH in relation to primary diagnosis and treatment, laboratory values, pathology studies, outcome of HLH after treatment, and overall survival. Conclusions: Two patients with acute myeloid leukemia (AML) and one with acute lymphoblastic leukemia (ALL) were diagnosed with HLH, having fulfilled the criteria as outlined in HLH 2004 protocol. They then received HLH specific treatment. One patient passed from refractory HLH, one from primary disease (i.e. AML) and one patient remains alive 22 months from her allogeneic bone marrow transplant. The diagnosis of HLH requires the presence of any of the five following criteria: fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis, low/absent NK cell activity, hyperferritinemia, and elevated soluble interleukin 2 receptor level. Due to its heterogeneous presentation, it remains imperative that treating clinicians remain cognizant about HLH so that prompt diagnosis may allow appropriate treatment. Two out of 3 patients in our study were in remission with regard to HLH, while 1 patient succumbed to refractory disease. We hope to improve awareness of HLH among pediatric oncologists that will lead to improved survival and better outcome for these patients.