Malignancy-associated hemophagocytic lymphohistiocytosis in children: a 10-year experience of a single pediatric hematology center

Abstract

Objective: Malignancy-associated hemophagocytic lymphohistiocytosis (M-HLH) in children is a relatively rare but life-threatening secondary hemophagocytic lymphohistiocytosis (sHLH). Until now, only a limited number of cases regarding children with M-HLH has been reported. Methods: We conducted a retrospective study of 27 children with M-HLH, who admitted to our center between July 2007 and October 2019. The clinical data and laboratory data were analyzed. Results: The median age of the children with M-HLH was 7 years. Underlying diseases included myeloid malignancy (n = 6), lymphoid malignancy (n = 18) and unknown type lymphoma (n = 3). The one-year mortality rate was 56%. All patients had persistent fever. The clinical manifestations included hepatomegaly (89%), splenomegaly (67%) and central nervous system symptoms (56%). Thirteen children (48%) had Epstein-Barr virus (EBV) infection. No significant differences were observed between EBV-positive and negative M-HLH patients in terms of most clinical indicators. However, EBV-positive M-HLH patients showed prolonged activated partial thromboplastin time (APTT) and more hemophagocytosis in the bone marrow (BM) in contrast to EBV-negative patients. Eighteen patients (67%) received the HLH-94/04 regimen as the initial treatment. There were no significant differences in the overall survival (OS) between EBV-positive and negative patients. Patients with prolonged APTT had a significantly poorer OS than other patients (p = 0.012). Conclusions: The M-HLH children with EBV infection are more likely to have prolonged APTT and more hemophagocytosis in BM. The M-HLH children had a poor prognosis, especially those with prolonged APTT.

Keywords: Children; Epstein–Barr virus; lymphoma; malignancy-associated hemophagocytic lymphohistiocytosis; prognosis; treatment‌; ‌activated partial thromboplastin time; ‌acute leukemia.