Shortly after our last update, Ellie had surgery to remove the large Post-Transplant Lymphoma Disease (PTLD) lymph node in her neck for testing. Unfortunately, by that stage her condition had deteriorated so she was re-admitted. We’ve been back in hospital for over a week now and I think we’ll be here for quite a while as there are several issues at play and we’ve had a few scares over the last week.
 
The removal of her lymph node went reasonably well, though there was some question about whether she was stable enough to have the surgery. The surgery went ahead and they were able to remove the majority of the lymph node. However, for the next 48 hours Ellie was in an extreme level of abdominal pain despite being heavily medicated, and extremely nauseated, vomiting considerable volumes of bright green, and then bloody vomits.
 
For several days her pain and nausea were not under control and we had no real explanation for what was happening. The current thinking is that it’s all related to the PTLD in her bowel and throat. After a few days of changing medications to try and find something that worked, we eventually got her pain under control by switching from Fentanyl to Hydromorphone PCA, and a few other pain medications. She is now basically back to having about a dozen medications running through her central line around the clock, plus TPN and nasogastric feeds. It very much feels like being back to square one. Other symptomology includes a head cold which she’s had for months. No immune system means she can’t get rid of it. She is terribly congested, can’t breathe through her nose, and she has fluid in her ears. Her hearing is so poor we have to speak very loudly and so she can lip read. She also can’t hear herself speak, so when she talks she sounds like she’s deaf.
 
It's also now evident that the first plan for treating her EBV and PTLD has failed. She has shown no clinical response since the Rituximab infusions commenced and her EBV count has continued to increase considerably. There were a few days where we thought we had some success as her bloods showed no signs of EBV. However, it turned out they were actually not HER bloods, but a different Ellie Carter, incorrectly entered into her profile. But we won’t talk too much about that. They were very quick to lodge an incident report, and we’re just thankful that no decisions were made to alter her treatment based on the incorrect information.
 
The good news (sort of) is that the results of the lymphoma biopsy confirmed PTLD, caused by her EBV, and not a more sinister type of cancer. Granted, the PTLD diagnosis isn’t good news but at least it isn’t a more sinister lymphoma which would be bad news. We’ll take what we can get at this point.
 
The new plan for PTLD treatment is the donor Cytotoxic T-Cell Lymphocyte (TCL) treatment. After speaking with one of the head oncologists, we’ve since learned that this is a real opportunity. I’m not aware of it being performed in Australia before and we only have access to it because our oncologist has some experience performing it in America, though as I understand, it’s only been performed in around 500 patients. Our oncologist was part of a study which used CTLs to treat EBV with good results. The theory is, the donor T-Cells will boost her immune system for a short period of time and target the EBV and PTLD, hopefully eradicating it. We have secured 6 batches of infusions which are given in 3-4 week intervals and the donor T-Cells eventually die after around 6-8 weeks. While an opportunity, it also comes with risk. Cytokine Release Syndrome (CRS) and GvHD are the main ones were concerned about. There’s also the risk that it doesn’t work which would make us almost out of options.
 
Since the first infusion of CTLs on Friday, Ellie has been highly febrile, has respiratory difficulty and significantly elevated CRP (inflammation) markers. She’s now reliant on oxygen and we had a scare yesterday morning which almost resulted in another ICU admission. She’s since stabilised but we don’t really know what the cause is. By now, we’re very used to being told ‘we don’t know why this is happening’. This particular incident could be the CTLs, PTLD, EBV, or a new underlying infection that is brewing. We’ve changed up her anti-biotics and anti-fungals again and added some broader-spectrum anti-biotics to be sure. So far, nothing has grown on her cultures, but a chest x-ray shows some minor collapsing of her lungs. This is likely the reason she is now reliant on oxygen however, we still don’t know the cause of the other reactions.
 
It’s a difficult time right now, and we can see Ellie deteriorating. We’re just hopeful that the CTLs have an effect and give Ellie a chance. If not, our last chance could be more chemo but I know there are serious questions about how much we could/should give her at this stage.
 
On a brighter note, Ed Sheeran visited the hospital yesterday. He wasn’t allowed to come up to Ellie’s isolation room and Ellie wasn’t allowed to go down to the Starlight Room to watch but the nurses arranged for him to say a few words to her. He said “a big hello to Ellie Carter, I’m sorry I couldn’t come up to see you but hope you’re feeling better soon” which was televised on the internal hospital TV network. Of course Kara took a video of it all, and then the video of Ellie and the nurses dancing to Ed Sheeran was sent back to the Starlight room for Ed to see and that was also televised on the hospital TV. Ellie was very chuffed by this and it put her in good spirits for the rest of the day. The ward was buzzing all afternoon.
 
While clinically, Ellie is not doing so well and she’s under High Acuity care, she’s surprisingly in good spirits. Since her pain and nausea are under control, she’s alert, talking, eating, and maintaining a sense of humour. Despite everything else going on around her, it makes a huge difference when she’s in good spirits. There are nurses on the ward who have literally never heard Ellie talk in the last 2 years and they’ve been coming into the room just to have a chat with her.
 
We continue to look for the silver linings, but they appear to be fewer and fewer. We’re doing our best to stay positive and are hopeful that CTL therapy will give Ellie the boost that she needs.  
 
 
PC[...]

It hasn’t been the start to 2023 that we had hoped for – with lots of ups and downs over the Christmas period and first few weeks of the new year.
 
As we know, Ellie has struggled with Graft vs Host Disease (GvHD) since around the time she was released from transplant. This has been treated with Prednisolone steroids and it has been our aim to wean her off the steroids as soon as we can due to the long-term complications associated. We have not been able to achieve this due to GvHD continually reoccurring. One of the major issues with continued steroid use is the prolonged weakened immune system. Prednisolone kills T-cells (which can cause GvHD) but it also doesn’t allow the immune system to recover. The longer Ellie doesn’t have an immune system, the more likely she will develop life-threatening infection or complications.
 
So here we are. Ellie has now been diagnosed with Post-Transplant Lymphoproliferative Disease (PTLD). It is essentially a form of lymphoma disease. While it is cancer, it’s caused by EBV and therefore different to most forms of cancerous lymphoma. (I don’t really know what this means but I think it sounds like a softer blow). She has dozens on PTLD lumps present in her neck, tonsils, and bowel. As I understand it, this is also not a relapse in that it is not AML. It's a different type of cancer, basically caused by the treatment for her other cancer (AML).
 
We have been tracking that Ellie has tested positive to Epstein Bar Virus (glandular fever) for a few months, but her levels weren’t significant enough to treat. Then about 2 weeks ago, her EBV levels spiked significantly. This was cause for concern, and the team ordered a CT scan, followed by PET scan. The PET scan confirmed PTLD with a significant number of lumps in her bowel, tonsils, and a large lump in her neck.
 
Unfortunately, many of her symptoms are consistent with both GvHD and PTLD (diarrhea, nausea, stomach pain, sore throat, skin rash etc). Ellie’s stomach pain has been extreme for a couple of months, so PTLD in her bowel makes a lot of sense. GvHD is much more common and therefore we have been treating her with Prednisolone. Also unfortunate is that the Prednisolone has essentially been working against her, allowing EBV and therefore PTLD to grow. It is likely the Prednisolone has been masking the growth of PTLD.
 
In the past, our oncologist has referred to this phase of treatment/management as a black art, because there is no play book and not enough data/evidence to support what we’re doing. We also know Ellie has had some rare complications, and our oncologist reinforced that we are again in ‘the rare of the rare’ territory. Engraftment syndrome, GvHD, EBV, and now PTLD is incredibly rare. There simply is no evidence to clearly guide us through the next steps.
 
I asked the oncologist if it was possible that Ellie has GvHD and PTLD. His response was “Yes, and if that’s the case, we’re in real trouble.” This would be a real problem as we’re about to stop the drugs that fight GvHD so we can commence the drugs that fight PTLD.
 
Notwithstanding, our oncologist has a plan – and a backup plan – like he always does.
 
Ellie will undergo four infusions of Rituximab over four weeks. Each infusion takes six hours and will destroy her B-Cells. Note that we have already destroyed her T-Cells with Prednisolone however, EBV apparently hides in the B-Cells. We will cease Prednisolone to try and grow her T-Cells again.
 
Ellie will also undergo EBV-cytotoxic T Lymphocyte (CTL) therapy. This is ‘kind of like another transplant but not really’. It’s a type of immunotherapy which ‘transplants’ donor-matched T-Cells to fight PTLD. Again, not much data available to support but apparently, it’s the new thing to try. We’ve been told we don’t know what the optimum dose is, but we’re going to get her as much of the good stuff as we can. Apparently, there is a donor-matched quantity in a Brisbane donor bank and we’ve placed an order for as much as they’ve got.
 
The back-up plan is to have an operation to remove the large PTLD lump in Ellie’s neck for the purpose of biopsy and tissue testing. This will likely happen in the next week. It won’t necessarily change the way we immediately treat however, if the treatment plan fails, then we can confirm the exact DNA makeup of the cancer and therefore treat with the correct chemotherapy. We hope it doesn’t come to that, as it will be another very delicate dance, given the extent of toxicity already administered over the course of the last 2 years. The tissue testing will also be used in (yet another) ‘Rare Cancer Sub-study’ to better understand what causes and how to treat rare cancers.
 
Risks? Yep, lots. All the normal stuff – none of which we really want to think about. But at this stage, we just need to try to remain positive and try everything that’s available. As Kara said in her last post, we are ever grateful to kiss and hug Ellie, and have her home with us every day that we can.
 
PC[...]

It is two years ago today, 6 February 2021, that Ellie received her diagnosis.  We despair over the fact that Ellie hasn’t been truly “living”, not living life the way you or I do. Not having fulfilling experiences such as swimming in the ocean, going on a hike, waking up feeling energised or well rested, not feeling hopeful about what the day will bring or the weekend will bring. The days run together for her with chronic pain, nausea and fatigue. Her choices revolve around what to eat or drink and what to watch on Netflix or YouTube. [...]