This week has been another week of ups and downs. We were on track for early release until Ellie spiked a temp last Friday. As we know, a temp is the first sign that something is brewing and unfortunately, it never lies.
 
It is now believed Ellie does have engraftment syndrome. This is not good news and not something we were expecting. Engraftment syndrome is very difficult to define and there are some academic parameters but nothing that is black and white. This is why the team initially thought it was just some form of immunologic response.
 
As we understand, it is not GvHD (graft attacking Ellie’s body), and not graft failure (Ellie’s body rejecting the graft) as we saw the early signs of engraftment. However, since the engraftment signs of strong white cell and neutrophil recovery, we then saw a sharp decline back to pre-engraftment levels. I posed the question to the team “If it’s not GvHD, and we know engraftment commenced, to what extent can this immunologic response result in subsequent graft failure; can that happen?”. Unfortunately, the answer was yes, it can happen, and yes, it’s possible that is what we’re seeing. They then explained the concept of ‘secondary graft failure’. Again, something that was not initially explained to us.
 
What it looks like for Ellie is high temps and reduced oxygenation, requiring oxygen support. There doesn’t appear to be any fluid in her lungs and she doesn’t have pulmonary edema. The team is now in the middle of another juggling act. Steroids to calm the immunologic response, but not too much that it completely inhibits her developing immune system and damages her kidneys. The steroids have had good effect so far – her oxygenation has improved and counts have begun to recover, but her temps are inconsistent. We need to ‘wait and see’ what happens over the next few days when the steroids wear off.
 
There is also the ongoing suspicion that there may be another infection brewing or that we were never able to properly clear her previous infections. They have been doing viral tests which have all been negative and blood cultures daily. Yesterday a blood culture tested positive for micrococcus luteus again and her temps have been high but inconsistent. Interestingly, we stopped Vancamycin the day before she tested positive again. Now she’s back on the Vanc and the plan is to again ‘wait and see’ what happens in the next couple of days. The fact that she’s had irregular ‘fleeting’ positive cultures is concerning in that it potentially points to a small infection that is unable to be cleared. We know that Ellie isn’t growing the infection due to the antibiotics, but it keeps inconsistently popping up in blood cultures.
 
Ellie also recently had another echocardiogram to see if the infection was attached to one of her heart valves. The echo shows that her heart is looking ok and no trace of the infection. However, there is some fluid surrounding her heart which is consistent with inflammation and recent infection.
 
The current thought is that the micrococcus luteus possibly never went away but was just suppressed by the Vanc, hence it hasn’t showed on every culture. If we can’t get rid of it in the next 48 hours, its presumed that it’s stuck on Ellie’s central line. As we have previously written, Gram-positive bacteria stick to plastic. In some cases, they stick to the central line and are extremely difficult to remove with antibiotics. The only way to remove it, is to remove Ellie’s central line. The Infectious Disease team is already advising to remove Ellie’s central line however, our oncology team are treading cautiously and will only remove it if absolutely necessary due to the risk involved in a general anaesthetic, given Ellie’s current condition.
 
So, again, the plan is to ‘wait and see’. Wait and see what happens when the steroids suppressing the engraftment syndrome wear off and wait and see if we’re able to clear her infection.
 
It looks like we’re going to be in hospital for a little longer than expected. We really don’t know what will happen in the next few weeks and we feel like we’re back in limbo, just playing the waiting game.
 
Despite the fact that we’re all suffering ‘transplant fatigue’ Ellie is otherwise doing well. I can see that spark in her eye starting to come back, and she occasionally fires up with her cheek and sharp wit. Today she logged into her school robot and whizzed around the class while they were having a free-play hour. Seeing her friends brought a big smile to her face and reminded her about what to look forward to.  
 
PC[...]

Hi Family and Friends,

Paul and I wanted to post another update as less than 24 hours after the "good news" post, Ellie had a setback.[...]

What a difference a few days can make. Since our last update, Ellie has really turned the corner. The team is happy to declare that engraftment is achieved, and Ellie’s bone marrow is starting to regenerate. Based on her neutrophil recovery, they have determined effective engraftment date was D+14 which is about as good as you can get. Ellie’s neutrophils jumped from 0.0 to 1.02 and as high as 1.46 before dropping a little, stabilising around 1.0. We should see her counts slowly increase over time as her bone marrow and immune system regenerates.
 
For comparison, last year it took 5 months post-treatment for Ellie’s neutrophils to reach 1.4 and she achieved that in just 2 weeks this time. That demonstrates the power of healthy donor stems cells, kick-started with some GCSF to promote white cell growth.
 
The team are also confident that her quick engraftment is due to the perfect 8/8 HLA matched donor cord blood. I had previously written about the benefit of umbilical cord donor blood vice traditional bone marrow donor, and the team at the Randwick Kids Cancer Centre are confident about this being the next best thing from a matched sibling donor.
 
The other important news is that we have not seen any signs of acute GvHD which is also attributed to the HLA matched cord. We still need to be vigilant for early signs of GvHD as it can occur within the first 100 days of engraftment. However, not seeing it now is a positive sign and indicates that its less likely she will have chronic GvHD in the future. We’ve also been reassured that the lack of GvHD does not necessarily mean the Graft v Leukaemia (GvL) effect is not occurring. We clearly want the new cells to attack any remaining Leukaemia cells. It seems a bit of a black art to find the balance. Ellie is on Cyclosporin for GvHD prophylaxis however, it is also an immunosuppressant. After 60 days, if no GvHD is seen, she will wean off the Cyclosporin to allow her immune system to take over and potentially give way to a degree of GvHD but importantly, promote the GvL effect. It’s critical that Ellie’s new immune system has the capacity to deal with any remaining Leukaemia cells.
 
For now, Ellie has really turned the corner. She is feeling much better, eating a tonne, communicating and has energy for Lego, reading, and small activities. She is still very fatigued, can’t walk well, and has nerve and limb pain however, this is to be expected for several months post-transplant.
 
The team are so impressed with her progress in the last week that they are starting to plan for her discharge! This includes reducing anti-nausea medication, reducing the Fentanyl background, and switching some IV medications to NG Tube in preparation for release. They are talking about release potentially by the end of next week which would be one week earlier than planned.
 
So far, BMT has been an absolute emotional rollercoaster for us. Silver linings and positivity have been hard to find at times and we’ve had some of our darkest moments over the last month or so. While we are certainly not in the clear yet, this week has only brought positive news, and we are optimistic about the future.
 
If Ellie is discharged late next week, it will be almost exactly one year since she was discharged from hospital following treatment in 2021.
 
PC[...]

Thank you to everyone who has reached out and continue to support us during Ellie’s BMT. We want to keep everyone’s mind at ease during this period and will aim for weekly updates.
 
Since our last update, Ellie has continued to struggle physically and emotionally however, without any major complications. There have been a few close calls. As we know, one of the major challenges is avoiding the smallest infections that could prove life-threatening.
 
In the last week, Ellie has had 3 infections, though all seem to be under control with several antibiotics. The first was streptococcal pharyngitis (Strep) which we believe started in her mouth due to the mucositis. It then entered the blood through her open mouth sores. The problem with Strep is it apparently sticks to plastic so the concern is it could stick to her central line which runs through her heart and enables her to receive all critical medication. This would mean we need to remove and replace her central line, which is a significant surgery and one that she is not stable enough to undergo. Thankfully, the strep appears to have cleared, though she will remain on Clindamycin antibiotics for a further 10 days.
 
Ellies second infection was staphylococcus. Staph can come from anywhere and is commonly found on the skin. It could have been caused by any one of us not cleaning something well enough, or just from Ellie’s own skin which is why we shower her every day and are extremely careful with hygiene. This also appears to be under control with vancomycin antibiotics.
 
Ellie’s third infection which was confirmed today is believed to be micrococcus luteus, another bacteria commonly found on the skin. We’re still waiting for clarity on the sensitivity of this bacteria to antibiotics however, we understand it is likely sensitive to Vancomycin and Clindamycin.
 
Ellie is on a range of other medications for several other ‘smaller’ issues that we’re working through. These include consistent high blood pressure, blood, protein, and glucose in her urine, low potassium levels, fluid retention, and a heart murmur. These all point to reduced major organ function, but nothing that has flagged as a serious concern yet. I’ve mentioned in the past that much of the trauma Ellie has endured has become normalised. In any other circumstance, we would be concerned by just one of these issues. However, all things considered, they are of lesser concern right now.
 
Ellie is now on constant Fentanyl (morphine) background with a Patient Controlled Button Analgesia (PCA) button for pain break-through. The background has been increased a couple of times to keep on top of the pain and it seems to be working reasonably well. She’s mainly in pain due to mouth sores, mucositis, gut pain, and regular nerve pain in her side, shoulders, back, and legs.
 
The good news is the nausea and vomiting has almost completely subsided, so her appetite is returning. In the last few days, she’s been eating soft foods and lots of cereal. This is actually a big win, and the team are particularly impressed as its common for kids to not eat for weeks on end during transplant. It means she will be less reliant on TPN and nasogastric feeds in the medium term. In fact, she isn’t on TPN yet which we had expected.
 
The other early sign of some good news is today, her White Cell count appears to have jumped up to 1.5. A jump from 0.0 to 1.5 is a considerable jump for a neutropenic child. There was also an early indicator of neutrophil count recovery commencement however, we will monitor this over the next few days. If indeed her WCC and neutrophils are starting to recover, it signals the beginning of engraftment. This is excellent, but also a little scary as we’re entering GvHD territory – one of our biggest concerns.
 
So, the next 1-2 weeks could either be really good with blood count recovery due to engraftment and hopefully Ellie starting to feel better, or really bad due to GvHD. We have our fingers crossed and are optimistic for the former.
 
Despite all the pain she’s enduring, Ellie still manages to occasionally give us a cheeky smile such as in the attached photo.
 
PC[...]

Well, this is really tough. I don't know what else to say.

It's been10 days since the last update when the stem cells were pushed into Ellie's body via her central line.  Days +1 to +5 were pretty good. She was pretty upbeat, in and out of bed, doing activities chatty, and eating and drinking. But, then on Day +6, things started to turn. More meds as per the program were introduced, and the mucositis in Ellie's mouth started to develop. The past 4 days have been awful, with Ellie at her lowest point since relapse. She won't speak very much due to the pain in her mouth. She often lies in bed doing nothing as she has no desire to engage in activities and she is sleeping quite a lot. Her BP is elevated and she was started on an anti-hypertensive, Amlodipine. This has just been increased today as she was requiring even more medication for breakthrough hypertension (Nifedipine). She was started on a Fentanyl PCA bolus only, but that was quickly increased to include a background (constant dose) plus the bolus dose that she can deliver herself with the click of a button when she needs it. She is good about using this as needed, before getting out of bed to go to the toilet or as she is waking up in the morning. Her urine output has glucose and protein in it and the team is watching her closely for any declining function in her kidneys. She is already on defibritide to protect her from veno-occlusive disease (as mentioned in a previous post) but more may need to be done. Her blood sugars are going up marginally as a side effect from the steroids she has now started. She will require insulin if this continues. [...]

Just a quick update to let everyone know Ellie’s Bone Marrow Transplant went ahead today as planned. Everything went well, with no major immediate reactions. As I’ve said before, stem cell transplant theory is fascinating. Our anxiety has been building over the last few weeks and we were all feeling a little nervous about today. It’s crazy to believe this little 37ml bag could be what saves Ellie’s life.
 
Ellie did fantastically and seemed unphased by the transplant. She’s been very sick for the last week or so with constant nausea and vomiting. She doesn’t have much energy so was just resting and watching a movie during the momentous occasion. She hasn’t been talking and barely communicating for the last week but was able to nod/shake her head when asked if she was in pain and if she understood what was happening. I could tell that she was paying attention and was aware of everything happening around her.
 
While Ellie has largely ‘shut down’ hilariously, she sometimes randomly perks up for 30 seconds to make a sharp comment (usually directed at a nurse or us) which catches everyone off guard. During the transplant infusion, she commented that it ‘tasted like old yoghurt’. The transplant team found this interesting as a common reaction is an awful taste which induces vomiting, but they were impressed with the description of ‘old yoghurt’. The old yoghurt smell was quite potent when Ellie exhaled, and it lingers around the room for some time.
 
It will now take a couple of weeks for the fresh stem cells to fully bed-down in the long bones and for engraftment to occur. Over the next 2 weeks, we will hopefully see the chemotherapy induced nausea and vomiting start to subside. Chemo has now done its job and Ellie’s bone marrow has been destroyed. She won’t have any more chemo, hopefully ever. While the nausea should subside, we’re now entering mucositis territory which has already commenced. This will likely result in extremely painful mouth sores and gut pain for which the team are planning to put her straight on constant fentanyl (morphine). Hopefully, from D+14 we will start to see signs of engraftment which, will include a degree of GvHD, as I’ve explained in previous posts.
 
The next few weeks are going to be difficult for Ellie. We all have strong hopes for quick engraftment without major complications.
 
Thank you to everyone for the continued love and support. Please keep Ellie in your thoughts.
 
PC[...]

The last couple of days Ellie has started some of the major medications and chemotherapy to condition her for transplant. It’s been a hard few days and Ellie is really feeling the effects of the Busulfan chemotherapy. Its didn’t take long for side effects to start and she has been constantly nauseated and vomiting. The team continually change up the medications to find the balance and I think we recently had a breakthrough with the vomiting as that has slowed, however the nausea remains. She has stopped eating and drinking so she’ll probably be on nasogastric feeds and Total Parenteral Nutrition by Sunday/Monday. We’re lucky she hasn’t had any of the major and rare side effects and we have our fingers crossed it stays this way. We know that she is going to get sicker, but we still hope for no major complications.
 
It's a strange feeling to look at her in her sick state and try to imagine what’s happening inside. It’s not just a matter of being nauseated; we know her bone marrow is being completely destroyed right now. I can’t imagine what that feels like. I tried saying to her to just close her eyes and rest ‘because when I feel really sick, it helps to close my eyes and try to sleep.’ I felt like an idiot after saying that as any sickness I have felt can never compare to what she’s feeling right now.
 
We have a laminated copy of the ‘game plan’ in the room and I have attached a photo. So far Ellie has started:
 
Pentamidine to prevent PCP
Lipo Amphotericin for fungal infection
Ursodeoxycholic acid and Defibrotide to prevent VOD for which Ellie is high risk due to previous Gemtuzumab
Levetiracetam to prevent seizures brought on by Busulfan
Cefapine for broad spectrum antibiotic
Metoclopramide, Ondansetron, Cyclizine, and Aprepitant for nausea.
 
All of this is to combat the effects and complications caused by Busulfan chemotherapy and ATGAM. ATGAM is an immunosuppressive drug that boosts the effects of the chemotherapy to ensure it destroys the immune system and any remaining lymphocytes that could reject the donor cells. Over the weekend, the Busulfan will cease and Cyclophosphamide chemotherapy will commence, along with Cyclosporin for GvHD prophylaxis.
 
Ellie is now ‘shutting down’ like she did during the horrific induction therapy in 2021. However, she is doing so with what seems to be more of an awareness of what’s happening. She still communications with some head nods or frowns but that’s about it. But it’s all we need for now; just to know she’s still here with us.
 
The whole operation is much more tightly controlled than previously. Every drug needs to be given at very specific times and before administering them, the nurses warn us what to expect and what ‘could’ happen. Our head oncologist, who lucky for us is also the head of transplant and soon to be head of the department, offhandedly remarked ‘yeah I’ve already yelled at someone for not having one of the meds ready in time.’ I think it was a matter of about half an hour but it meant everything else had to be pushed back. He’s generally unflappable but we can see these types of situations are very stressful for the staff. During some of the more dangerous meds, we practically have a nurse in the room with us all the time, watching for any strange side-effects and constantly doing observations. It’s very tense. 
 
I realise we didn’t provide an update on the possibility of brain radiation. It’s a long and complicated (and emotional) story. The short story is we’re not doing it because it can’t be determined if it’s actually necessary; the side effects of ‘significant irreversible cognitive decline’ are life-long and too risky for something that is not indicated; and there is no evidence to show that it would benefit AML in the brain (even if it were still present). The fact is that AML in the brain like Ellie had is so rare that nobody in the Kids Cancer Centre has ever seen it that we’re aware of, and there is no data on its treatment. Experimentation on the brain, knowing the cognition side effects is not something we’re comfortable with.
 
Despite everything happening, we’re impressed with Ellie’s attitude. Everything is a struggle – meds, mouth care, showing, toilet – but she’s doing it all the best she can.
 
D-0, Transplant Day is Monday 4th July.
 
PC[...]