Post-Transplant Lymphoproliferative Disease

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