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. [...]

New Year, New Ellie

 [...]

The last month has been a little rough for Ellie, adjusting to changes in her medications. Since coming off the Prednisolone steroids, things haven’t been as smooth as we hoped. It’s obvious to us now, just how much the steroids were doing for her. The purpose was to prevent GvHD however the side effects included mood swings, huge appetite and others as we’ve spoken about. Since stopping the steroids, Ellie has regularly been nauseated, vomiting, diarrhoea, and generally feeling off.
 
We recently increased her anti-nausea medication as she was struggling to hold anything down. She vomited so much that she brought up her nasogastric tube. This was obviously a little distressful for her, as she was vomiting while the long tube which was in her stomach was now hanging out her mouth. We quickly cut the long end and pulled the rest out through her nose. It was a bit of an ordeal at bed time!
 
After a few days, we had the NG tube replaced, which also isn’t a pleasant experience. However, a few hours after getting home, Ellie vomited it up again. Back to square one. We cut and pulled it through her nose again, and then had it replaced a few days later. So far it has remained in place; let’s hope it stays that way! We think the NG tube will need to stay for a few more months until Ellie no longer needs to take cyclosporin; she can drink enough fluid during the day; and her food intake is good enough to not need NG feeds. 
 
There was a period of concern last week when Ellie had blood in her vomit over a few days. However, the team believes she may have a little tear in her oesophagus which is causing the blood rather than anything more sinister.
 
The vomiting, diarrhoea, and blood in her vomit sounded alarm bells for us that GvHD was returning after ceasing the steroids. This has also been a concern for the team however, they have been cautious not to jump into treatment as her symptoms weren’t entirely consistent with GvHD. However, things escalated over the last week as the diarrhoea and vomiting hasn’t improved, Ellie’s weight has been dropping, and now she has a rash starting to reappear.
 
The head oncologist declared today that Ellie has GvHD again and has ordered us to recommence steroids. His plan is to ‘go hard, early’ to kill the T-Cells that are attacking Ellie’s gut and skin, and then wean back from the steroids ‘after time’. Ellie will commence steroids tonight, around four-times the dose she was taking when we completed BMT. This also means Ellie will have to continue taking cyclosporin. Prednisolone steroids and cyclosporin are two of the key medications that have long-term side effects, so we had hoped to stop taking them as soon as possible. Now, it looks like she may need to take them for at least another 2-3 months.
 
This is a significant regression in Ellie’s recovery which is clearly disappointing. However, the silver-lining remains that GvHD likely also means a Graft vs Leukaemia effect. Therefore, the graft should also be attacking any remaining leukaemia cells. The other silver-lining is that Ellie is still home with us, and in pretty good spirits. She’s doing full days of school via her robot, and next week will participate (Robo-Ellie presence) in the school assembly/concert for Grand-mother’s Day.
 
PC[...]

It’s been about one month since our last update and we’re pleased to report that Ellie is doing really well and feeling pretty good. During the last hospital stay where Ellie spiked a temp and we ran her into emergency, no infections were detected in her line and we were released after about a week of antibiotics. Since then, it’s been relatively smooth sailing.
 
Ellie is now attending weekly clinic appointments for bloods and check-ups and this will probably continue for a few more months before her central line is removed. This is much less of an impost than having to go in three times per week as we were doing before her last temp, and it means that we all have a much more normal routine.
 
We have been weaning back several medications over the last few months and Ellie is now completely off the Prednisolone steroids which is a big milestone. The steroids were responsible for her uncontrollable appetite (she has put on around 6kg since diagnosis and has the steroid chipmunk cheeks), significant mood swings, and muscle atrophy. Being off the steroids means her moods have stabilised and her appetite is back to normal. I think she’s starting to feel a little more normal too.
 
She is still taking Cyclosporin, Posaconazole, Bactrim, Amlodipine, Omeprazole, Magnesium, and Ondansetron.
 
Ellie is starting to get her energy and strength back, and a key indicator is that she can usually get up and down the stairs by herself. She’s also interacting more and really enjoying Annabelle’s company – they’re like best friends again!
 
We also love the fact that she has enough energy for full days of school via the MissingSchools robot. The robot has been amazing for her, and she participates in all her classes, does all her school work, and is able to interact with her friends on a daily basis.
 
We know that we have a long way to go, but for now, Ellie is improving every week and getting closer to feeling normal. She can’t wait for Summer, with hope that her central line will come out in time for her to go swimming at the beach again!
 
PC[...]

We had our first trip to the emergency department this week with Ellie spiking a fever on Wednesday evening. She had a clinic appointment that day, and they accessed her central line to take bloods per usual. The thought is that some bacteria was introduced into her line at that time, which caused her fever just a few hours later.
 
Ellie spiked an unusually high temp which reached 40C very quickly. The team believe it is likely a gram-negative bacterium due to the high temp. Once in emergency, Ellie was administered Cefepime and Gentamycin antibiotics immediately while blood cultures were taken. We’re lucky to live so close to the hospital as we’re required to get her to the ED within 30 mins of spiking a temp. Once at the ED, we flash the ‘gold card’ which gives the triage nurse specific instructions to immediately admit her and commence Cefepime as soon as possible. It’s a pretty efficient process so there’s no waiting around in the same room as other sick kids. We remained in an isolation room in emergency for about 24hrs until an isolation room became available on the paediatric oncology ward.
 
Since being admitted, Ellie’s blood cultures haven’t grown any bacteria so we may not know what the cause of her temp was. It’s possible to have a situational temperature which isn’t caused by anything specific however, due to the very high temp, this is unlikely. It could have been a small amount of bacteria which was quickly cleared by the antibiotics and therefore hasn’t appeared on the cultures. This would be ideal as it means Ellie should be released soon. If her cultures are positive, then she will be committed to a 7-10 day course of antibiotics, and would have to stay in hospital likely for around 2 weeks. However, if her cultures are negative, then after around 5 days she could be released providing she doesn’t have any more temperatures and is otherwise stable. We are therefore hoping she can be released as early as Monday or Tuesday.
 
Aside from this minor setback, Ellie has been progressing well. We can notice the positive effect being at home has on her emotional state and she appears to be getting some of her strength back from moving around the house and playing with Chewie.
 
Fingers crossed we’ll be home again soon.
 
PC[...]

We’re excited to say that Ellie was released home earlier this week and is enjoying being back in her own environment with her puppy and her sister. It has been great having the whole family back under one roof again and not needing to share time between the hospital and home.
 
It has been another challenging transition and we’ve had some friction along the way. There was some miscommunication about the necessity for a new central line. Initially we were told a new central line would not be required and we could make do with cannulas however, this advice has now changed. The two long cannulas that were placed last week both failed within the week. Additionally, Ellie can’t be released home with a cannula, so every time we go back in for bloods, it requires more needle sticks. The team have decided that Ellie will need a new central line placed next week. This is just another GA that we didn’t want and surgically placing another line into her heart comes with more risk as it will be the third time. While it would hopefully only be needed for around 2 months before being removed, the thought is that Ellie will still need blood product support and when she spikes a temp, they will need to commence antibiotics within 30 mins, so relying on cannulas won’t be sufficient.
 
We are also required to attend clinic appointments three times a week where bloods are drawn and blood products may be required. This is challenging without a central line as Ellie has developed what seems to almost be a phobia of needles. She’s not so bad with regular needle sticks for drawing blood however, cannulas are very challenging. Her veins are extremely difficult to access, and they almost always roll or collapse. The only way to access them is by having an anaesthetist use an ultrasound to guide the needle. This results in Ellie usually being stuck 3 or 4 times before successfully having the cannula inserted. It takes considerable effort to mentally prepare her for a regular needle and we need to physically restrain her for cannulas. Ellie now says she wants to have the central line back in to avoid more needles.
 
The good news is that Ellie’s GvHD appears to be under control. It has not progressed beyond stage 1 GvHD and her rash has responded to the Methylpred steroids. The rash is barely noticeable and she isn’t bothered by itching. The Methylpred will likely last for another 8-9 weeks.  
 
It’s a full-on job looking after Ellie at home. We’re back in the routine of administering half a dozen medications through her NG tube twice daily, giving her water boluses regularly to flush the medications from her kidneys, and NG tube feeds throughout the night. She is still very weak and needs assistance walking, eating, dressing, washing, and most other activities. We’re trying to get her back into a school routine where she can zoom-in via her ‘Missing Schools’ robot which lives in her classroom however, getting her to participate is challenging.
 
Ellie’s confidence has taken a real beating throughout treatment, which is most evident with her communication and decision making. We had noticed this after completion of treatment last year and it’s even more evident since transplant. She struggles to communicate with her teacher and friends during school sessions and her ability to make simple decisions about what to do or what to eat is almost non-existent. We know she is very intelligent however, we also know she is starting to miss key learning milestones. To compensate, we are developing a plan to have a private tutor come to the house twice weekly to get her back on track and reduce any longer-term learning issues. She is also really struggling emotionally so we are looking at options for emotional/psychological support which I can see as being an ongoing requirement as she progresses through school and needs additional support coping with all the normal stresses of childhood and teenage years. We feel it is best to get on top of some support networks sooner rather than later.
 
Silver linings: Ellie is home with her puppy and her family, and this is great for her mental health; the whole family is back under the same roof and this is great for everyone’s mental health; GvHD and engraftment syndrome are both under control and we consider that there are no ‘major problems’ right now; Ellie’s counts are recovering well and her white cells and neutrophils are at a level we haven’t seen since first diagnosis (11.7, 9.36); so all things considered, Ellie is doing reasonably well.
 
We remain optimistic that Ellie will continue to improve with every day.  
 
PC[...]

This week started off with the decision to remove Ellie’s central line due to the presumption that it was infected and the reason for several positive cultures. She had another positive culture on 29 July – another staph infection and was highly febrile for about a week. That was enough to make the call on removing the line which occurred on 2 Aug. This was done under general anaesthetic, and everything went well, though Ellie was extremely nervous about the procedure.
 
Ellie now has two ‘long cannulas’, one in each arm, for IV medications. While not ideal, its workable considering we are in the process of weaning her off several medications and transitioning most to oral in preparation for an eventual discharge. Ellie now takes most medications through her nasogastric tube which will continue when she is released home.
 
The bad news is Ellie is now suffering Graft v Host Disease – one of our major concerns with transplant. The day after removing her central line, Ellie broke out in a rash covering 25-50% of her body. Rash is one of the first indicators of GvHD and she was soon diagnosed with the disease. This is coincidental to the line removal – really bad timing, but not related. The rash coincided with a steady decline in her white cell and neutrophil count which, to this point, had been steadily improving after successful treatment for Engraftment Syndrome. GvHD is a bone marrow suppressant and therefore impacts graft growth and this accounts for the decline in her counts. The donor cells are now attacking various healthy cells in Ellie’s body which at this stage, seems to be just limited to her skin. This results in a skin rash which is extremely itchy and very distressing for Ellie.
 
Ellie is being treated with three different antihistamines, four different skin creams, and importantly, Methylprednisolone steroids to treat the GvHD and reduce inflammation. Unfortunately, treatment with Methylpred is likely to run over 8-10 weeks. While it’s not such a big deal in the short term, we know there are several long-term side effects and can cause diabetes. Ellie already has a concentration of glucose in her urine and if this continues, she will need insulin. When Ellie was being treated with Methylpred (0.5mg p/kg) for the Engraftment Syndrome, the team reassured us by saying we shouldn’t be too concerned because it’s not as if she is having GvHD-size dosage (1.5mg p/kg). This reassurance has clearly backfired as Ellie is now being treated with 2.0mg p/kg. We understand this will continue for 7 days before being reduced to 1.5 for 7 days and then reassessment.
 
Critically, we need to see Ellie’s counts recover to demonstrate the graft is recovering from the GvHD. Her symptoms of GvHD could last for weeks however, the Methylpred should allow her graft to grow and her white cell and neutrophil counts to recover.
 
Thankfully, Ellie’s GvHD is currently Grade 1 (mild): Skin rash over less than 25% of the body (though its actually 25-50% in Ellie’s case but with no other symptoms). We need to be watchful for additional symptoms which characterise the following grades:
 
Grade 2 (moderate): a skin rash over a more than 25% of the body, accompanied
by mild liver or stomach and intestinal disorders.
 
Grade 3 (severe): redness of the skin, similar to a severe sunburn,
and moderate liver, stomach and intestinal problems.
 
Grade 4 (life-threatening): blistering, peeling skin, and severe liver, stomach, and
intestinal problems
 
The silver lining in dealing with GvHD is that we don’t expect any severe GvHD because Ellie’s cord donor is perfect 8/8 HLA match. Also, a degree of GvHD indicates the possibility of a degree of Graft v Leukaemia (GvL) effect. So, the hope is that while the graft is attacking Ellie’s healthy cells, it’s also attacking any residual Leukaemia cells which would clearly reduce the chance of another relapse.
 
To us, it feels like setback after setback. Since first diagnosis, Ellie has had several unfavourable outcomes, ultimately leading to relapse and BMT. Now, during BMT she’s had six infections, central line removal, Engraftment Syndrome, and GvHD. It’s extremely fatiguing for us and for Ellie, and sometimes defeating.
 
However, in our perpetual search for silver linings, we know things could be worse. The team continue to reassure us that in the context of BMT, she’s actually doing reasonably well. When we were preparing for BMT, our head oncologist said to us “there’s a chance Ellie will go into that room and never come out again”. Those haunting words revisit us every time we have a setback. But we’re still here and Ellie is still fighting.
 
With any luck, we will be able to get on top of the GvHD soon, wean down the Methylpred, and transition all her medications to oral. So long as the infections stay away and Ellie doesn’t spike a temp, we could have her home within a week or so. We’re anxious to get her home as soon as possible, purely for her mental health and we have seen how well she bounces back when she’s home with her family and her puppy. In the last 17 months since Feb 21, Ellie has spent 10 months in hospital.
 
PC[...]

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[...]