Throw The Kitchen Sink At It

I’m overdue for another update. Blogging is normally therapeutic for me, but I’ve had a hard time sitting down and completing this one. Beginning with the end in mind for my people who don’t love to read long blogs, we’re still fighting rejection, we’ve officially reached the stage of chronic antibody-mediated rejection (HLA class 2), and we’re exploring the possibility of relisting for a second transplant.

It’s hard to even write that.  There is no guaranteed therapy for this rejection. They have therapies that have worked for others, and they have essentially thrown the kitchen sink at it at this point. His body just isn’t responding the way it needs to.

Since my last formal update, we did two more hospital stays. One was another two-week stay with Plex + IVIG and Carfilzomib instead of Rituximab. Carfilzomib is technically a type of chemotherapy, which is intended to kill fast-growing cells. It’s used to treat Multiple Myeloma, a blood cancer that develops in your b-cells. Danny doesn’t have Multiple Myeloma, but it was interesting to see a medication serve different diseases for the same purpose! While Rituximab was intended to render the B cells useless, the Carfilzomib’s job was to break communication between T-cells and B-cells. There is a subset of T-cells that tell your B-cells to go create antibodies, and we wanted those two types of cells to just stop talking to each other. The cadence was similar to the previous hospital stay. 17 days. 8 Plex. 8 IVIG. 4 Carfilzomib infusions.

It was the most entertaining hospital stay we’ve had. The neighbor in the room next door took us on a wild journey with his loud music, screaming phone calls, and daily order of 4 Cream of Wheats with 4 brown sugars and a Diet Coke. I had a lot of empathy for that guy from all the things I learned listening to him as he angrily yelled or sobbed in every conversation, and I hope he’s doing well, but I also hope I never see him again, too. #Tom.

The final hospital stay was right before Christmas. His donor-specific antibody levels had crept back up a bit. The most his DQ7 tested at was 6,000. It had gone down to 3,000 and increased back to 4,000. His DQ8 had maxed at 14,000, went down to 7500, and went back up to 9000.  This time they tried a therapy called, Antithymocyte Globulin (ATG). ATG can be derived from rabbits or horses, and Danny’s therapy was rabbit. They inject human white blood cells (lymphocytes) into the animal, and the animal’s immune system produces antibodies against the human cells. The antibodies are collected, and that’s your medicine. This stay was only 7 days, and he was out December 19^th

The plan post-discharge was to go into monthly IVIG infusions with another drug called Tocilizumab. That drug is designed to attack IL-6, which is a part of your immune system that regulates inflammation as well as the development and activation of T-cells and B-cells. Tocilizumab is not normally used for lung rejection so it required an appeal through insurance to go off-label, and his insurance actually agreed to allow it for him and for others should they get another request for the same use. That’s a victory worth mentioning.

In January, he entertained an esophageal manometry test. This involves putting a catheter with pressure sensors up your nose, down your throat, and into your stomach to test how well your esophagus is functioning when you swallow food and liquid. The whole procedure/test only lasts around 20 minutes, but it was pretty terrible. His gag reflex is pretty reliable and made for some pretty violent gagging and vomiting.  They followed this test up with a 24-hour pH monitor, which involves removing the bigger tube and replacing it with a smaller (yet still irritating) catheter that stays in for 24 hours to monitor your pH levels to check for GERD.  It’s possible that silent reflux could lead to damage to the lung graft if it’s aspirated. Both of these tests came back negative for any issues.

At some point, there was also a scan of his sinuses and another bronchoscopy or two. All of these tests were ultimately ruling out other potential causes of chronic rejection, which helps make him eligible for additional treatments when you’re trying to get insurance to make exceptions for you.

In February, his home spirometry testing was dropping again. It goes up and down from day to day, which gives hope and takes it away; however, the trend overall was down. He was far more symptomatic than he had been in the prior months with fatigue, weight loss, coughing, and a tight chest. Because of the drop in lung function, they suggested adding Photopheresis into the treatment plan with the goal being to preserve lung function. ATG was mentioned again; however, you can only safely receive ATG a certain number of times without risk because it’s a systemic treatment. So he got a Vortex port placed at the beginning of the month in order to handle the Photopheresis treatments.

During Photopheresis, blood is taken from the body into a machine that extracts the lymphocytes. The machine adds a medication to the lymphocytes that activates when they’re exposed to light. Then the machine hits them with a UVA light and sends them back into your body. This changes the way the lymphocytes behave and can prevent them from damaging the lung graft. The process lasts around 3 hours, and he had little to no symptoms from the treatment. It does make your eyes sensitive to light even if you can’t feel it, so they give you some neat wraparound sunglasses to wear outside AND wraparound clear glasses to wear inside to filter out harmful lights for 24 hours. Around 60% of patients see stabilization in lung function with this treatment. The first two treatments are done in one week, and the following week has another two treatments. After that, he does one treatment in two weeks and then settles into a monthly cadence for a total of six months.

With all that said, we ultimately don’t feel optimistic about the efficacy of the treatment options he has left, and we’re starting to run out of options as well. We looked at a graph of his pulmonary function test results from 2019 to February 2023 during his last appointment. In 2019, he was incredibly low until his transplant in June, where you see a dramatic spike into a more normal range. He holds that function range consistently until September 2022. Then it drops and comes up and drops and comes up on a micro level, but ultimately when you step back and look at the last 5 months at a macro level, it’s a drastic drop. He’s nearing pre-transplant function levels, and we’re starting to have discussions with the care team about another transplant.

That’s a whole separate blog to write…