Hemophagocytic Lymphohistiocytosis: Clinical Review at the Philippine Children&rsquo;s Medical Center

Maria Beatriz    P. Gepte,; Maria Luz  O. Del Rosario,; Eustacia  M. Rigor,

Hemophagocytic Lymphohistiocytosis: Clinical Review at the Philippine Children’s Medical Center

Maria Beatriz P. Gepte | Maria Luz O. Del Rosario | Eustacia M. Rigor

Abstract:

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by extreme immune activation, resulting in pathologic inflammation that may be life-threatening. Early recognition is crucial since survival largely depends on early initiation of treatment which utilizes a combination of chemotherapy, immunotherapy and in some cases even bone marrow transplantation. OBJECTIVES: This study aims to describe the clinical characteristics, treatment received and outcome of patients diagnosed with HLH at the Philippine Children’s Medical Center from 2004 to 2017 MATERIALS AND METHODS: A retrospective analysis of records of children 0 -18 years of age diagnosed with HLH from January 2004 to December 2017 was done. RESULTS: A total of 39 patients were included in the study which gave an incidence of 1.22 per 3000 patients admitted under 18 years of age. There were 29 males (74.4%) and 10 females (25.6%) with a male to female ratio of 2.9:1 Mean age was 6.12 ± 3.89 years. The average time from initial presentation to diagnosis was 6 weeks and 2 days. The most commonly seen clinical and laboratory features observed in these patients were fever (100%), splenomegaly (71.8%), anemia (87.17%), thrombocytopenia (79.48%) and hypertriglyceridemia (69.23%). Only 5 patients were confirmed to be familial HLH with 3 having XLP gene mutation, and one each having syntaxin and perforin gene mutations. Majority of patients received a combination of treatment based on the HLH 2004 regimen while almost one third only received antibiotics. Only 23% of patients survived during the study period and all but one of these patients received drug combinations based on the HLH 2004 protocol. CONCLUSIONS AND RECOMMENDATIONS: HLH is a rare but important condition that must be recognized early and treated appropriately to optimize survival. The mortality rate of 39 patients seen in this institution is high. There is a need to better utilize the diagnostic criteria of the disease and to employ a more uniform treatment strategy. Increasing awareness among health care personnel can also improve case finding, characterization and treatment.

References:

Henter, J.-I., Elinder, G., Soder, O., & Ost, A. (1991). Incidence in Sweden and Clinical Features of Familial Hemophagocytic Lymphohistiocytosis. Acta Pediatrica Scandinavica , 428-435.
Janka, G., Imashuku, S., Elinder, G., Schneider, M., & Henter, J.-I. (1998). Infection- and Malignancy- Associated Hemophagocytic Syndromes. Hematology/Oncology Clinics of North America , 12 (2), 435-444.
Egeler, R., Shapiro, R., Loechelt, B., & Filipovich, A. (1996). Characteristic Immune Abnormalities in Hemophagocytic Lymphohistiocytosis. Journal of Pediatric Hematology Oncology , 18 (4), 340-345.
Ullah, W., Abdullah, H., Qadir, S., & Shahzad, M. (2016). Haemophagocytic lymphohistiocytosis (HLH): a rare but potentially fatal association with Plasmodium vivax malaria. BMJ Case Report , 1-4.
Meeths, M., Horne, A., Sabel, M., Bryceson, Y., & Henter, J.-I. (2015). Incidence and Clinical Presentation of Primary Hemophagocytic Lymphohistiocytosis in Sweden. Pediatric Blood & Cancer , 62 (2), 346-352.
Niece, J., Rogers, Z., Ahmad, N., Langevin, A.-M., & McClain, K. (2010). Hemophagocytic Lymphohistiocytosis in Texas: Observations on Ethnicity and Race. Pediatric Blood & Cancer , 54, 424–428.
Ishii, E., Ohga, S., Imashuku, S., Yasukawa, M., Tsuda, H., Miura, I., et al. (2007). Nationwide Survey of Hemophagocytic Lymphohistiocytosis in Japan. International Journal of Hematology , 86, 58-65.
Gurgey, A., Gogus, S., Ozyurek, E., Aslan, D., Gumruk, F., Cetin, M., et al. (2003). Primary Hemophagocytic Lymphohistiocytosis in Turkish Children. Pediatric Hematology and Oncology , 20, 367-371.
Henter, J.-I., Horne, A., Aricó, M., Egeler, R.M., Filipovich, A.H., Imashuku, S., Ladisch, S., McClain, K., Webb, D., Winiarski, J. and Janka, G. (2007). HLH- 2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatric blood & cancer, [online] 48(2), pp.124–31.
Villaluz, M, Manahan, L, Gepte, B, Robles, J. Hemophagocytic lymphohistiocytosis: A rare case of primary CNS involvement in a Filipino Child.Herdin 20, March 2012
Yu, M.G. and Chua, J. (2016) Virus-associated haemophagocytic lymphohistiocytosis in a young Filipino man: BMJ Case Reports, p.bcr2016214655.
Lovisari, F., Terzi, V., Lippi, M.G., Brioschi, P.R. and Fumagalli, R. (2017) Hemophagocytic lymphohistiocytosis complicated by multiorgan failure. Medicine. 96(50), p.e9198.
Gokce, M., Balta, G., Unal, S., Oguz, K., Cetin, M. and Gumruk, F. (2012) Spinal cord involvement in a child with familial hemophagocytic lymphohistiocytosis. Journal of Pediatric Neurosciences. 7(3), p.194.
Allen CE, Yu X, Kozinetz CA, McClain KL. (2008)Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohis- tiocytosis. Pediatr Blood Cancer. 50:1227- 1235.
Basu, S., Maji, B., Barman, S. and Ghosh, A. (2017). Hyperferritinemia in Hemophagocytic Lymphohistiocytosis: A Single Institution Experience in Pediatric Patients. Indian Journal of Clinical Biochemistry, 33(1), pp.108–112.
Larroche C, Bruneel F, André MH, Bader-Meunier B, Baruchel A, Tribout B, Genereau T, Zunic P. (2000) Intravenously administered gamma-globulins in reactive hemaphagocytic syndrome. Multicenter study to assess their importance, by the immunoglobulins group of experts of CEDIT of the AP-HP. Ann Med Interne (Paris). 2000 Nov;151(7):533-539.
Bergsten, E., Horne, A., Aricó, M., Astigarraga, I., Egeler, R.M., Filipovich, A.H., Ishii, E., Janka, G., Ladisch, S., Lehmberg, K., McClain, K.L., Minkov, M., Montgomery, S., Nanduri, V., Rosso, D. and Henter, J.-I. (2017). Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood, [online] 130(25), pp.2728–2738.
Malinowska, I., Machaczka, M., Popko, K., Siwicka, A., Salamonowicz, M. and Nasiłowska-Adamska, B. (2014). Hemophagocytic Syndrome in Children and Adults. Archivum Immunologiae et Therapiae Experimentalis, [online] 62(5), pp.385–394.