Details of Yzzy’s bone marrow transplant

We need to talk about Yssabelle Eddlemon. Don’t worry. She’s fine.

In the eleven months since her HSCT (hematopoietic stem cell transplant, often called bone marrow transplant), Yzzy has become a bone fide legend in the mast cell community. The reason why is obvious: she has been cured of her mast cell disease, something the rest of us can only dream of. But the thing about legends is the facts sometimes get lost.

I have been contacted several times by families who want to contact her care team or the details of her treatment protocol/transplant procedure. So I would like to clarify what happened to Yzzy that necessitated a transplant and how it cured her.

Firstly, Yzzy did not have MCAS. She had SM, true, meets WHO criteria, just like in adults, SM. This is actually how our paths first crossed: she had dense colon infiltration like me, which isn’t terribly common. Yzzy had markers of progression of her SM towards a malignant form called aggressive systemic mastocytosis (ASM). She was already a very sick little girl when I met her and she got a lot sicker in the years that followed.

By February 2016, Yzzy was completely TPN dependent. She couldn’t take anything by mouth. She had mast cell reactions every day and anaphylaxis regularly. Her anaphylaxis episodes were terrifyingly fast. I’m talking seconds to administer epi. She spent a lot of time admitted to manage her anaphylaxis and complications of her SM, including central line infections. Her liver and spleen were swollen. She had very enlarged lymph nodes throughout her abdomen. Her kidney function wasn’t great. She had a ton of airway inflammation. Her GI tract was infiltrated by mast cells. She was a mess.

Around that time, Yzzy started having these bizarre, frightening episodes. She would spike a high fever (105°F and higher), get an awful headache, and become very nauseous. Eventually, the episodes also started causing significant upper GI bleeding, sometimes enough to require a transfusion. She would sometimes be unresponsive.

Patients with central lines are recommended to present to an ER if they have a fever over 100.5°F so she went to the hospital when it happened. They never had any idea what was wrong with her. There was never any indication that it was a line infection. After 3-4 days, the fevers would just resolve and she would recover. These episodes were also triggering her SM so anaphylaxis complicated these episodes further. Yzzy had a total of 22 episodes by the time anyone figured what was wrong.

In September 2016, a rheumatologist who happened to be covering the ER treated Yzzy when she had one of these episodes. For the first time, he thought he knew what was wrong with her. After a bunch of testing including bone marrow biopsies, she was diagnosed with a rare condition called hemophagocytic lymphohistiocytosis (HLH). HLH causes certain cells called macrophages to attack red blood cells, literally eating them. The red cells would break open, releasing chemicals, causing an inflammatory cascade called cytokine storm. The cytokine storm would cause the fever and the rest of the symptoms. The macrophages caused significant damage to her bone marrow.

We tried to avoid chemo when she was diagnosed. She did immunotherapy treatments for about two months. They weren’t stopping the episodes and she was decompensating fast. In November, Yzzy’s hematologist told us that he did not expect Yzzy to survive without a transplant and the odds of surviving the induction chemo and transplant were about 50% at best. But we had tried every other treatment and none of them were stopping the HLH. We had no choice. She was going to die without a transplant.

When Yzzy was diagnosed with HLH, she got a bunch of new doctors, none of whom knew much about mast cell disease. You may have read the Provider Primers series I wrote. These are primers I wrote for her new doctors. I also wrote a white paper on Yzzy, basically a manual for what to do in various situations. I highlighted important papers and sent them to her care team. And when it became obvious she was having a transplant, I aggressively advocated for them to use a specific myeloablative chemo protocol because there was a chance that could cure her SM. They agreed.

The four weeks before her transplant almost killed her. There was many times that I thought this was the end. The chemo destroyed her body. Her SM was the least of my concerns. But she survived the chemo and on January 12, she had the transplant.

Many of you know the story from this point – Yzzy’s body accepted the transplant and she improved steadily. Her SM is gone. Her HLH is gone. Her immunodeficiency is gone. She no longer needed TPN. She could eat a full, normal diet. Her port was removed. She hasn’t had anaphylaxis since the transplant. She is healthy. She is in second grade and goes to regular full day school. She takes one medication for her transplant and she will stop that med in January. She is off everything else. She is a miracle.

Yzzy got her transplant not because she had SM but because she had HLH, which would have been fatal. There was no other play. It was this or death. She would not have been eligible for transplant based upon SM alone. There are a few pilot programs for transplant in patients with ASM or MCL. They all require patients to have exhausted all other treatment options and to have terminal disease staging.

People who receive their transplants FOR their ASM or MCL do not do well. Currently, there are a few patients alive after four years, but they are very sick. The other patients have all died.  However, SM patients who get transplants for another disease sometimes do pretty well. This is the group Yzzy is in.

Keep in mind that Yzzy’s SM was not secondary to her HLH. That’s not why transplant cured her SM. SM is always a primary disorder. HLH is also a primary disorder. She would have gotten SM or HLH even if she had not had the other one. The reason the transplant cured her SM is because the chemo killed off her defective bone marrow that gave rise to her defective mast cells. Because SM is inherently a bone marrow/blood disorder, if the original bone marrow is effectively killed, the SM could be cured by replacing the bone marrow with healthy bone marrow. That’s what happened with Yzzy.

Unfortunately, Yzzy’s transplant has no bearing at all on MCAS patients as there is no transplant option for MCAS. I have been contacted by two people about pediatric ASM patients who will likely need a transplant at some point. If you are in this group of people, feel free to contact me. But keep in mind that Yzzy’s team had no real training in SM aside from me educating them. We kept her at that hospital for other, more complicated reasons. So the team who managed her transplant won’t be able to help other SM patients.  

If you have any questions about Yzzy’s transplant, please let me know and I will be happy to share.

Xoxo,

 

Lisa