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Updates on Diagnosis and Treatment of Hemophagocytic Lymphohistiocytosis Tsung-Yen Chang, M.D.. Division of Pediatric Hematology/Oncology Linkou Chang Gung Memorial Hospital Sep.. Inter

Updates on Diagnosis and Treatment of

Hemophagocytic Lymphohistiocytosis

Tsung-Yen Chang, M.D.

Division of Pediatric Hematology/Oncology

Linkou Chang Gung Memorial Hospital

Sep 2019

Case 1

•16+ y/o boy Intermittent fever for 10 days

•In community hospital

• Abdominal echogram: mild splenomegaly

• Hepatitis survey: negative

Case 1 (cont’)

Case 2

•0 d/o boy Abdominal distention after birth

•In community hospital

• PE: hepatosplenomegaly

• Hemogram:

• WBC: 5300/ul, Hb: 12g/dL, Plt: 14k/ul

• Biochemistry:

• AST: 58, ALT: 16, Bil D/T: 3/9.3

Case 3

•2 y/o girl Intermittent fever for 3 days

•In community hospital,

• Abdominal echogram: hepatosplenomegaly

• Hemogram:

• WBC: 3200/ul, Plt: 72k/ul

• Biochemistry:

• AST: 685, ALT: 678, Bil D/T: 2.8/4

2ndrelapse

Discussion

Introduction of HLH

•HLH is characterized by fever and

hepatosplenomegaly, CNS symptoms, cytopenias,

coagulopathy, and lipid changes

•HLH occurs in all age groups

•A hallmark of HLH is impaired or absent function of

NK cells and cytotoxic T cells

•HLH can classified into two distinct forms, primary

and secondary HLH

Blood Rev 2007;21(5):245-53.

lymphohistiocytosis (FHL)

•Primary HLH is caused by inborn defects in the

primary cytotoxicity effector pathway in

lymphocytes and NK cells

•Autosomal Recessive, Incidence: 1:50,000

•Median survival is <2 months if left untreated

•Onset is typically during infancy or early childhood

•May be triggered by infection

Hematol Oncol Clin North Am 2015;29(5):895-902.

Diagnostic Workup

•Flow cytometry

• Surface expression of perforin/granzyme B and SLAM

associated protein (SAP) and intracecullar expression of

XIAP

• Surface CD107a

•NK cell activity

• 51 chromium release assay

•Molecular testing

Diagnostic Algorithm

Hematol Oncol Clin North Am 2015;29(5):895-902.

•Review of 32 children in CGCH (1992-2007)

• Except for 6 fatal cases before 1998, 26 patients had

genetic analysis for the PFR1, Mun13-4, and STX11

genes.

• Twelve male patients further received SH2D1A (located

at X-chromosome) sequencing.

• None of any 4 mutations was identified.

Pediatr Infect Dis J 2009;28(1):30-4.

The pathophysiology in EBV HLH

Crit Rev Oncol Hematol 2002 Dec;44(3):259-72.

Blood 2011;118(17):4577-84.

Blood 2017;130(25):2728-2738.

Overall survival of all 73 Japanese children

treated with HLH 2004 protocol

Int J Hematol 2019;109(2):206-213 2019 Annual Meeting of TPOG on 2019/01/13