Thread by @Eddie_Cliff

Fantastic heme grand rounds on HLH at @DanaFarber @BrighamHeme today from @ZorefAdi @CCHMCPostdoc - a 🧵

Starting with a timeline, the pathogenesis and defining the clinical syndrome of HLH
#HLH #lymsm (1/8)

How to diagnose HLH? Soluble CD25 and ferritin are the most specific inflammatory markers (best ROC), so @ZorefAdi et al combined them into an 'optimised HLH inflammatory' (OHI) index, with an improved specificity for HLH

ashpublications.org/blood/article/… @BloodJournal (2/8)

Once you have made the diagnosis of HLH, the next step is to find the underlying cause.

Great flowchart from Paul La Rosée et al in @BloodJournal: ashpublications.org/blood/article/…

A tip: 'lymphadenopathy is not a symptom of HLH so should raise suspicion for underlying lymphoma' (3/8)

As you see from the flowchart - if you can achieve remission of HLH, the next step is to consider allogeneic stem cell transplantation

Gooptu et al @DrCCutler @DrLaCasce published promising @DanaFarber outcomes of alloSCT for HLH ashpublications.org/bloodadvances/… @BloodAdvances (4/8)

How to treat lymphoma-associated HLH?
A two-step approach:
1. control the hyperinflammation
2. treat the underlying malignancy

"Current approaches are not enough to improve the outcomes for these patients"

Table from review in @TheLancetHaem thelancet.com/journals/lanha… (5/8)

Next @ZorefAdi divides patients w malignancy-assoc HLH into those w inflammatory phenotypes (OHI+) versus those w/out, finding those w/out die mostly from underlying progressive disease whereas those w inflammation die mostly from multi-organ failure ashpublications.org/blood/article/… (6/8)

The paradox of HLH treatment: how to separate friend from foe?

"T-cell activation drives inflammation in familial HLH but it is essential for tumour surveillance. Or is this the 'dark side' of a hot 🔥 tumour microenvironment?" (7/8)

Conclusion & Tips:
- early CD25 & ferritin to ensure you have the right diagnosis
- hunt for underlying cause, make sure to do viral PCRs not just serologies
- consider pros and cons of timing of corticosteroids

Thanks for a great talk @ZorefAdi! (8/8)