HLH

Question 1

HLH pathophysiology

Answer 1

• impaired cytolytic activity of T cells and NK cells
• Uncontrolled T cell activation with increased secretion of Th1 cyotkines (IFN gamma, IL-12, IL-18) which activate macrophages
• macrophages than phagocytose RBCs

Question 2

Pathophys of inherited forms of HLH + gene mutation

Answer 2

Mutations in perforin (resides in granules of NK cells and CTLs. They are released into the synapse between CT land target cells and they make “pores” in the target cell membrane, which allows entry of granzymes and other apoptosis, resulting in killing of target cells

Question 3

Novel HLH therapy for familial HLH + mechanism

Answer 3

1) Emapalumab
2) anti-IFN gamma
*No published data on results and responses aren’t that great so low utility for adults

Question 4

Other novel HLH therapy

Answer 4

JAK inhibitors (cytokines released act through JAK/STAT pathway) (currently in clinical trials)

Question 5

Relapsed refractory HLH management

Answer 5

Allogeneic hematopoetic stem cell transplantation

Question 6

Most aggressive pathogen in infection associated HLH

Answer 6

EBV

Question 7

What is the umbrella term for ICANS/CRS/ETC?

Answer 7

Post IEC (immunoeffector cell) hyperinflammatory syndromes