Charles Milrod, MD Profile picture
May 30, 2023 10 tweets 5 min read Read on X
Picture this:

A patient presents with an enlarging neck mass, and you find this 👇 on your evaluation.

What’s going on? 🤔

A #tweetorial 🧵 1/8 Illustration of lymphadenop...Reed-Sternberg cell from pa...
To guide our thoughts, let’s start with two Hodgkin lymphoma (HL) facts-

1) Cancer cells can ⬆️ PD-L1, which interacts with T-cells’ PD-1 and ⬇️ immune activity

2) 🔑 Immune checkpoint inhibitors (ICIs) block the PD-1/PD-L1 interaction & have strong activity in HL 👇

🧵 2/8 Image
Why do immune checkpoint inhibitors have such strong activity in HL? 🤔

🧵 3/8
The answer is both!

Chromosome 9p24 gains are common in HL and ⬆️ PD-L1/2 levels

🔑 Higher PD-L1 levels are associated with better response

Check out this connection below 👇

🧵 4/8 Image
T-regulatory cells are immunosuppressive!

🔑 Compared to reactive lymph nodes, HL has ⬆️ T-regulatory cells and markers of exhaustion👇

… but why would T-cell exhaustion be a *positive* predictor of response? 🤔

🧵 5/8 Image
In head & neck cancer, those who respond to ICIs tend to have *higher* levels of exhausted T- cells 👇

🔑 ICIs may have a “cytotoxic revival” effect on exhausted T-cell populations

Possible mechanisms include ICIs 👉 ⬆️ cytotoxic genes and ⬇️ of exhaustive genes

🧵 6/8 Image
Future of ICIs? 🤔

In the frontline for advanced HL, SWOG 1826 is evaluating Nivo-AVD vs BV-AVD.

Looking forward to this plenary session at #ASCO23! ⭐️

🧵 7/8 Image
Key takeaways:

🔑 Immune checkpoint inhibitors (ICIs) have strong activity in HL

🔑 9p24 amplification 👉 ⬆️ PD-L1

🔑 ICIs may have a “cytotoxic revival” on exhausted T-cells

… and food for thought:

🤔 Will SWOG1826 bring nivolumab to the front-line setting?

🧵 8/end
Thanks for sticking around- I hope you learned something new!

Thank you to @lymphomatic for the review 👏

I’d love to hear what the experts would add! @matthew_mei @graham74GC @DavidSteensma @myelomatic @Rcl14L @OllilaTom
For a deeper dive, citations are embedded in the pictures.

Pictures can be found here:

pubmed.ncbi.nlm.nih.gov/10594291/
pubmed.ncbi.nlm.nih.gov/10425256/

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More from @CharlesMilrod

Apr 12, 2023
It’s a great joy to share (and teach) what’s exciting about hematology!

Here are my go-to threads 🧵 for blood cancer fundamentals 👇
APML & DIC
Leukostasis
Read 14 tweets
Apr 4, 2023
Picture this:

Your patient with myeloma presents with hypercalcemia.

You find this 👇 on your evaluation.

How (and why) is this an emergency? 🤔

A #tweetorial 🧵 1/7
To guide our thoughts, let’s start with 2 hypercalcemia facts-

1) Severe hypercalcemia often presents with polyuria and dehydration

2) 🔑 Poor skin turgor is one of the more sensitive exam findings of dehydration 👇

🧵 2/7
With severe volume depletion in mind…

How does hypercalcemia cause dehydration? 🤔

🧵 3/7
Read 9 tweets
Feb 21, 2023
Picture this:

A patient presents with easy bruising, and you find this 👇 on your evaluation.

What’s going on? 🤔

A thread 🧵 1/6 Periorbital purpuraCongo red stain on kidney b...
To guide our thoughts, let’s start with two amyloid facts-

1) AL Amyloidosis is a syndrome caused by light chains depositing in organs

2) 🔑 Symptoms depend on the affected organ- these include:

- ❤️ heart disease
- 🫘 kidney disease
- 🙌 neuropathy

🧵 2/6
With excessive light chains in mind…

How does amyloidosis cause ⬆️ bruising? 🤔

🧵 3/6
Read 8 tweets
Jan 12, 2023
Picture this:

Your patient presents with a fever, and you find this 👇 1 week after starting treatment for APL.

What’s going on? 🤔

A thread 🧵 1/9 Chest x-ray with diffuse alveolar filling and effusionMany promyelocytes with auer rods
To guide our thoughts, let’s start with 2 acute promyelocytic leukemia (APL) facts-

1) The hallmark translocation of APL involves the retinoic acid receptor (RARA)

2) 🔑 The RARA translocation BLOCKS 🙅‍♂️ differentiation at the promyelocyte stage

🧵 2/9
2-year overall survival is ~99% with all-trans retinoic acid (ATRA) & arsenic

These have different mechanisms-

1️⃣ 🔑 ATRA interacts with RARA and induces differentiation

2️⃣ Arsenic causes cell death ☠️

🧵 3/9
Read 11 tweets
Dec 13, 2022
Picture this:

A patient presents with a headache, and you find this 👇 on your evaluation.

Why (and how) is this an emergency?

🧵 1/8 Skin tightening of fingers, curled inwardMany schistocytes
To guide our thoughts, here are 2 scleroderma renal crisis (SRC) facts-

1) SRC is a syndrome of kidney injury, elevated blood pressure, +/- hemolysis

2) 🔑 Prior to modern therapy, one-year mortality for SRC was 85-100%

🧵 2/8
Let’s break down the clinical triad -

1️⃣ Kidney injury
- from sclerosis of glomelular arterioles
👉 decreases renal perfusion

2️⃣ Elevated blood pressure
- from decreased perfusion sensed by JGA
👉 activates RAAS

With 3️⃣ hemolysis in mind…

🧵 3/8
Read 10 tweets
Dec 5, 2022
Picture this:

A young boy presents with mononucleosis, and you find this 👇 on your evaluation.

Why (and how) is this happening? 🤔

🧵 1/8 Icteric tongueRed blood cell agglutination
To guide our thoughts, let’s start with 2 autoimmune hemolytic anemia (AIHA) facts-

1) AIHA is caused by autoantibodies that bind & destroy RBCs

2) 🔑 Antibodies can be active at core temperature (warm 🥵) or below (cold 🥶)

🧵 2/8
🥵 Warm AIHA:
- IgG has 2 binding sites ✌️
- Destruction mostly by splenic macrophages

🥶 Cold agglutinin disease:
- IgM has 10 binding sites 👋👋
- Destruction by complement

🔑 IgM’s large size and 10 binding sites 👉 RBC agglutination

🧵 3/8
Read 10 tweets

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