hemophagocytic lymphohistiocytosis

Yeah.

That's the intro to our HLH episode, guys.

Although, other Nick, that sounds like you have excellently credentialed to be on the show.

Can I ask, where are you from? I'm

so when you say your spouse left you and you said it was a big why i mean you said selfishness what what was going on that caused her to say i'm done uh

so what caused her was uh so we were trying to have kids unfortunately we lost our first our first child and then once I found out the type of cancer or autoimmune disorder, it's called HLH, they said it's hereditary.

So we decided to not have kids anymore and they went, they said that they didn't want to continue our marriage because they wanted a family and so did I.

So things just didn't work out for us as we planned.

And then atypical lymphocytes that we mentioned before is also very classic for mono.

Some other less common presentations include aseptic meningitis, encephalitis, transverse myelitis, optic neuritis, cranial nerve palsy, the Alice in Wonderland syndrome, Guillain-Barré, splenic rupture, thrombocytopenia, hemolytic anemia, and cranial otocytosis, and HLH.

So all these are very rare, but I think you get tested the most on like splenic rupture.

Yeah, for sure, which we'll talk about in a bit actually.

Treatment is generally supportive.

Antivirals are not routinely recommended for mono.

But sometimes in severe diseases like with HLH or immunocompromised patients, we will give antivirals and immunomodulators.

But this is done with close consultation with infectious disease.

Like I had a patient actually recently, he was diagnosed with an inflammatory response, right? They thought this inflammatory response, I'll give you the name of it.

It's HLH, but it's this inflammatory response usually induced by some sort of cancer, lymphoma, leukemia, whatever it may be.

Sometimes it's induced by a virus.

Sometimes this inflammatory response...

But they labeled you with this diagnosis of an inflammatory response.

So when you walk out, you go, I know what I had.

What did you have? HLH.

You know what HLH translates to? Inflammatory response.

Knowing the signs can save a life.

This is Investigating HLH, a podcast about hemophagocytic lymphohistiocytosis brought to you by Sobe, Inc.

Hi, and welcome to another episode of Investigating HLH.

I'm Keri McGee.

Today we're here with a group of physicians whose work has shaped HLH.

So today we're actually going to talk about the story of CXCL9 and really where it started, how we understand how it's evolved, and what it might look like in the future and how it can help with diagnosis and treatment.

We're here with Dr. Michael Jordan from Cincinnati Children's.

Dr. Jordan, go ahead.

What are some of the chronic side effects that I need to keep in mind? Any lab checks along with ferritin, LDH that I should be keeping in mind?

Most of the time, the serious inflammatory toxicity, CRS, ICANS, and rarely an HLH-like syndrome will have resolved by the time the patient goes back to you, even by two to three weeks post CAR T.

So those should be handled before you receive them back.

I think the most significant long-term side effects tend to be cytopenias.

There's, of course, others as well.

One of the most dramatic manifestations of immune dysregulation, as we know, is HLH.

Maybe before we get into the details of what HLH is, could you maybe tell us where it sits in the spectrum of these primary immune regulatory disorders?

Yeah, so as I've mentioned, there are a few different buckets or categories of immune dysregulation or immune dysregulation disorders.

So HLH most of the time doesn't sit in the bucket of PERD because it typically is not related to regulatory T-cells.

but it is sort of its own category of immune dysregulation.

And I think maybe the most helpful thing to understand HLH is to first understand how a normal immune response terminates.

So in the setting of, let's say, an infection, The initial phases of the immune response have to do with recognition of the invader or of the antigen by myeloid cells or antigen-presenting cells.

I want, uh, that's why I wanted to read this to you.

"My wife recently got HLH." What is HLH, you say? Well, I'm gonna tell you what HLH is.

But I think, uh, and it's funny because that's how we think of illnesses.

We got them.

Not that we, our body has fallen apart, and our l- our, our life has been, you know, our lifestyle habits have been so dysfunctional or so counterproductive that our bodies start to exhibit dis-ease.

They fall out of ease.

The thinking is we got HLH, and it's not this guy's fault.

It's not Robert's fault.

We thought about ICANS.

In the second episode, we thought about HLH or, uh, macrophage activation syndrome, and we thought about the HATE score, we thought about the diagnosis and the management.

What I wanna do in this podcast, Anna, is pick up something that maybe we don't talk about enough, which is, how do we develop the services to be able to deliver the treatments? And I mean, when I say the treatments, I mean upstream as well from the treatment in terms of checking the patients, you know, able to have the treatment, we consent them properly, those bits.

Sometimes maybe a little bit neglected.

And then how do we manage in practice the, the, the cytokine release? We talked about that being within the hours, three to, you know, up to maybe 12, 14 hours.

So what do we need to do in that period? How then, if ICANS is gonna develop a few days after that, how do we get our treatment helplines to know how seriously to take these symptoms? And then HLH is, as you mentioned, is a, is a sort of a downstream sort of side effect, slight oversimplification, but let's go with it for now.

And therefore, how do we, you know, make sure those patients aren't missed? So let's sort of take it from the start, Anna.

Let's think about centers across the UK, but beyond the UK.

You know, if there's w- two rules in medicine that I like to say, one is if there are a bunch of criteria, probably nobody knows what they're talking about.

That includes Kawasaki and HLH and all these things.

And the other rule is if you see a wide range, probably nobody knows what they're talking about.

And so what I'll say is these, these guidelines were written looking at a ton of papers, but all the papers chose a random number and said longer and shorter.