Down at Kurnell Peninsula in southern Sydney. Missing our Ellie Bubbles but nice to be out in the sunshine with the three of us x[...]

We finally have confirmation of the excellent news that Ellie’s Bone Marrow Aspirate and Minimal Residual Disease Testing came back as MRD Negative (post C2)! This is fantastic as she continues to be considered in morphological remission with no trace of Leukaemia cells in her bone marrow! We are over the moon and this is a huge milestone as it determines the treatment plan for the remainder of her main treatment.
 
It’s also important to note that the MRD results were assessed using Polymerase Chain reaction (PCR) which is accurate to 1:100,000 cells and is considered definitive. This means Ellie has achieved MRD Negative (post C1 and C2) which categorises her as ‘Standard Risk’ (refer to my post of April 21). Standard Risk means she avoids the highly cardio-toxic chemotherapy and will finish her treatment in phase 3 and 4 with a more standardised chemotherapy treatment plan.
 
Ellie will be admitted tomorrow to commence Phase 3 treatment. She is currently still at home, which has been great, but is due to her blood results not yet showing that she is healthy enough to commence treatment. To commence Phase 3 she needs a neutrophil count of 0.75 however her last count last week was only 0.20. Bloods taken yesterday achieved 0.86 so she’s now ready to recommence treatment. For context, a healthy person’s ANC is around 1.50 – 1.80.
 
Today we also consented for another randomisation as part of the MyeChild Trial. Typically, Phase 3 and 4 AML patients who are Standard Risk are treated with high dose Cytarabine. However, the MyeChild Trial seeks to determine if incorporation of Fludarabine results in better long-term prognosis. Ellie will now be randomised for the two different treatment plans. That said, we understand the difference in the two treatment plans is not greatly significant, that is, they are both relatively ‘standard’ chemotherapies. Fludarabine does come with a slightly increased brain toxicity risk however, this is usually only evident in older patients, not children. Aside from that, we are fairly comfortable with the randomisation and the decision has not weighed on us as heavily as the Gemtuzumab randomisation from phase 1. In fact, we feel fortunate to have made it to consolidation therapy (phase 3 and 4) as we know there could have been many other outcomes.
 
It will be a total of 3 weeks that Ellie has been home during phase 2 recovery (less a number of day visits for bloods and check-ups). Once again, it has been amazing having her home and she’s loving being here with family, sleeping in her own bed, and playing with her sister. So much so that during some horseplay with Annabelle, she managed to rip her nasogastric tube out! I still have no idea how it happened. There was a little yelp and there it was, sitting on the floor. After some initial concern, Ellie thought it was hilarious. We also managed to convince the doctors not to put it back in because she has been eating a lot and taking all her medications orally. We will eventually need to put it back in during the course of phase 3 when she’s not capable of eating or taking oral medication.
 
One final note is that we are continually impressed with how Ellie is approaching her treatment. Her resilience in incredible. She fought so hard during the trauma of phase 1 and the grind of phase 2. We are now very lucky to be in a position to commence consolidation therapy after achieving Standard Risk prognosis. So many AML patients don’t get this far or are diverted to higher risk treatment plans. We now have the luxury of consenting to consolidation therapy randomisation rather than having to weigh our options as Intermediate or High Risk patients. When discussing the next steps and how long we will be in hospital, Ellie is pragmatic and mature. It must be hard for her knowing she is going back to hospital tomorrow for likely another 6 weeks but she doesn’t show it. She’s a fighter and determined to come out on top.
 
PC[...]

Just a short update to let everyone know that we finally got Ellie home for phase 2 recovery! She was released from hospital on Wednesday afternoon and we’re hoping to get 1-2 weeks at home before commencing phase 3.
 
We had hoped to get Ellie home a little sooner as she was progressing quite well however, another infection meant she needed to commence a new course of antibiotics. We had previously posted that Ellie was battling two infections – C Diff and Micrococcus Luteus. Those infections were treated successfully and she recovered quickly. However, we then discovered an infection on her skin, which was causing her quite a bit of pain. It took some time to confirm the type of infection while we waited for bacterial swabs, viral swabs, and blood cultures to reveal the source. During this period, she was being treated with Meropentin and Vancomycin, both broad spectrum antibiotics and so the doctors were confident they would be having an effect on the infection. The infection was eventually confirmed to be Pseudomonas Aeruginosa, which is unfortunately resistant to the two antibiotics being administered. Pseudomonas is a less common infection in the oncology ward and our team of doctors needed to rely on the dermatology team to determine the best treatment plan.
 
Ellie eventually commenced treatment with Aztreonam – an antibiotic unknown to the oncology team but recommended by dermatology. To complicate things, concurrent to the commencement of infection, Ellie’s neutrophils began to come back in after a long period of neutropenia. This is what had us thinking that she would be able to come home as soon as the Pseudomonas was treated and it was a good sign that her neutrophils were coming in even though she had an infection. However, shortly after commencing treatment with Aztreonam, Ellie’s neutrophils took a sharp turn downward. Aztreonam was having good effect on her infection however, it was causing neutropenia. One week after commencing Aztreonam, the decision was made to switch to Ciprofloxacin, a similar antibiotic but one which is less likely to affect neutrophils. After changing antibiotic, we immediately saw a sharp increase in Ellie’s neutrophils and we were back on track.
 
While we had technically not reached the normal trigger for home release (0.20 neutrophils) our team decided to release us as they were comfortable Ellie was trending in the right direction. It was also becoming a case of ‘now or never’ as our window for getting home was narrowing. Ellie is booked for her lumbar puncture and bone marrow aspirate on 12 May after missing the window for the 5 May booking due to not recovering quick enough. This gives us one full week at home before the LP+BMA. The plan is for this to be day surgery and all going well, Ellie can return home until the results of the Minimal Residual Disease testing are received and her treatment plan for phase 3 is confirmed.
 
Ellie is, of course, loving being home and we are loving having her home. It’s a full house with the four of us, grandma and Lilly. Ellie was so excited to meet Lilly after seeing lots of photos and telling all the nurses about ‘grandma’s puppy’ who is now living with us. We’re very fortunate to have all of us in the one house for mother’s day and again, its proving to be amazing for Ellie’s mental health.[...]

While we have largely been living Ellie’s journey one day at a time, particularly when things were rough and there’s a lot to process, we have always tried to keep informed of what subsequent steps await us in future courses. We have known there are a number of critical milestones, which must be achieved to progress through treatment with the best possible outcomes. If certain milestones are not met, it will set Ellie on a new path of treatment or on a course taking alternate medications that we want to avoid. Ultimately, we want to remain in the ‘standard risk’ category and avoid falling into the ‘high risk’ category which could see Ellie requiring stem cell transplant(s). Haemopoietic Stem Cell Transplant (HSCT) is very scary to us and we have been compartmentalising it to a degree, trying to not think about it and just focusing on what we need to do to remain in ‘standard risk’.
 
I have attached a photo of the AML MyeChild Trial Schema flow diagram, which has helped us to visualise Ellie’s treatment plan.
 
The outcome of phase 2 milestones has a significant impact on the remainder of Ellie’s treatment. The big milestone at the end of course 2 that we need to achieve is Minimal Residual Disease (MRD) ‘negative’ post course 2 (C2). This means achieving a negative result in testing for leukaemia cells in the bone marrow aspirate during MRD testing. Ellie currently sits in the Good Risk (GR) category based on her cytogenetics of Chromosome 16 Inversion (Inv(16)) which holds good prognosis. Given that she achieved MRD negative post course 1, based on the flow diagram, the only remaining variables and therefore possible outcomes of course 2 are: MRD negative post C2 (and C1) = Standard Risk; or MRD positive post C2 (neg C1) = Intermediate Risk.
 
If Ellie is MRD positive post C2 (Intermediate Risk) it will put her on a path to receive Fludarabine, Cytarabine, and Idarubicin (FLA-Ida) during course 3. This is a highly cardio-toxic chemotherapy, which we want to avoid as it increases the risk of cardio-vascular problems later in life, or during her immediate treatment. She has already received Mitoxantrone during course 1 and 2 which is also cardio-toxic. Then, if Ellie is MRD positive again post course 3, she will be on a path that leads to a stem cell transplant. It is possible for Ellie to be MRD positive post C2 when she was negative post C1 and we have been told this has happened in AML patients in the past in our ward. However, Ellie is lucky to have cytogenetics consistent with good prognosis (Inv(16)) which gives her a better chance of remaining MRD negative in C1 and C2.
 
If Ellie achieves MRD negative post C2 (Standard Risk) then she avoids the cardio-toxic chemotherapy. It will put her on a path where she is randomised for one of two treatment plans for course 3 and 4: high dose Cytarabine; or Fludarabine and Cytarabine. Both courses are very similar and there doesn’t appear to be a preferred option at this stage in the trial. In this scenario, following course 3 and 4 will see Ellie complete her main treatment. Following her main treatment, we don’t yet know what her residual treatment plan looks like and it will depend on how she responds after all four phases.
 
The MRD test conducted on Ellie’s bone marrow aspirate (BMA) is the same test that was conducted during phase 1 and I have written about this in previous posts. However, the technology used will be slightly different to phase 1. During phase 1 MRD using Flow Cytometry (FCM) was used, which is accurate to 1:10,000 cells. In phase 2 MRD using Polymerase Chain Reaction (PCR) will be used and is accurate to 1:100,000 cells. We had previously thought FCM was accurate to 1:100,000 however, this is incorrect and PCR will give us this increased fidelity.
 
We are currently in week 11 of treatment and 3 weeks into phase 2. Ellie continues to progress very well when compared to phase 1. She is feeling quite healthy despite being nauseated fairly regularly however, this is also beginning to subside. We are now playing the waiting game – waiting for her neutrophils, platelets, and white blood cell count to increase as they still remain at rock bottom. Amazingly, you couldn’t tell this by Ellie’s demeanour. We are hoping we can go home again soon for a week or so – just need to wait for the numbers to start talking!
 
PC[...]

Since commencing phase 2 treatment, Ellie is doing reasonably well. In fact, we would say she’s doing superbly when compared to the trauma of phase 1. The doctors have noted that her condition in phase 2 is more attuned to the norm and what we would have expected during treatment.
 
Despite her numbers being back down to rock bottom, she is in good spirits. Critically, her neutrophils are 0.00 and her platelets are sitting around 15 with blood transfusions every couple of days. Her haemoglobin is also on the way down and she requires red blood products a couple of times a week. This is exactly what we expected during this period after chemotherapy and it is, as we know, a game of closely managing her medications and trying to avoid infection. She is also regularly febrile however, unlike during phase 1 when this was around the clock, she responds very well to paracetamol and so the high temperatures aren’t affecting her too badly. While she is febrile, her temps are low-mid 38’s whereas during phase 1 she was consistently mid-high 39’s and even in the 40’s.
 
Ellie is also quite regularly nauseated however, again, unlike in phase 1, she communicates well and has good periods during the day where she feels well and is chatty, silly, and engages in school work, crafting, and other activities. Many of the nurses who looked after her in phase 1 find it amazing that she is now smiling and actually talking to them! It was a great novelty for the nurses to come in and have a conversation with Ellie. Many of them feel so relived and also a sense of victory that they have broken through with Ellie.
 
Although the aim of the game right now is to avoid infection, we have been in an isolation room for the duration of phase 2 due to a couple of infections. Shortly after being admitted for phase 2, Ellie was confirmed to have Clostridium difficile colitis (C Diff). This is a typical opportune infection that is regularly seen in leukaemia patients who are immunocompromised. It is being treated with Metronidazole and the doctors aren’t too concerned about it. Ellie was also recently confirmed to have Micrococcus Luteus, which was identified in blood cultures taken on 12 April. This is another opportune bacterial infection, which is being treated with Vancomycin.
 
Unfortunately, Ellie’s rash has returned. When she first spiked a fever, the go-to drug for treatment of an underlining but unidentified infection is Piperacillin Tazobactam (Piptazocin). This is the drug that we believed (but couldn’t confirm) was responsible for causing the horrendous traumatic rash during phase 1. When the rash returned, we immediately ceased Piptazocin and replaced it with Cefepime, another broad-spectrum antibiotic with very similar properties to Piptazocin.
 
We knew that because Piptazocin wasn’t confirmed as the cause of the rash reaction, the next time Ellie spiked a fever, they would administer Piptazocin. The dermatologist team suggested that if Piptazocin was actually the cause of the rash, we would see a reaction within 15 mins of administering the drug again. Ellie’s rash came back within 24 hours of the first dose of Pitazocin. Thankfully, it is much milder and less traumatic to Ellie as we immediately substituted drugs. To us, this confirms she is having a reaction to the Piptazocin however, there is some debate among the doctors. Some of the team are not convinced Piptazocin is the cause, whereas others believe it probably is. The best explanation we have is that it is likely a level 3 reaction (whatever that means) to one of the key components of Piptazocin. It is less clear because she didn’t have an immediate anaphylactic reaction and therefore, is not by definition, allergic to Piptazocin. In any regard, they will document it as being a drug related reaction, so that in the future, when she presents to hospital with a fever, Cafapine will be the go-to drug to treat rather than Piptazocin.
 
We feel quite comfortable with Ellie’s current condition and her overall response to phase 2 treatment so far. We’re hoping that we can maintain this level for a few more weeks until her neutrophils start to come back and she starts to recover from the chemotherapy. As a broad target, the last safe moment for a Bone Marrow Aspirate to be taken is day 42 (post phase 2 chemo commencing) so our window is 05-12 May. With any luck, Ellie will have recovered to a satisfactory level by that time so that we can complete the BMA and go home for a week or so (fingers crossed) while we await the BMA results. Phase 3 will commence shortly thereafter.
 
PC[...]

Well, as you all heard from our last post, Ellie had 9 amazing days at home! My heart was full having our family all in one place again. Ellie was back to her good old fun loving, happy, cheeky-at-times, self :) We had some laughs (and panics!) getting used to doing all of her meds at home. A pretty intense schedule that made us realise all that the nurses do for us around the clock. I had received a quick demo on operating her kangaroo feeding pump before we left the hospital, as well as a run down on all of the meds and how to take them in the new, non-IV route. It all seemed pretty straightforward and operating the pump came back to me like riding a bike! However, when it came time for the 9 PM feed to be set up and I tried to prime the line, I didn't know (or remember) to take the cap off the line and then couldn't figure out why it wasn't priming. Oh, goodness, I was out of practice!!! I had to call the ward at 9 PM to ask for help! (In my defence the nurse didn't show me that part haha). Ellie had this terrified look in her eyes like "Mom, you're going to kill me!" and said "Maybe I should go back to the hospital?". Of course I proudly and confidently said nonsense! We can DO THIS! I'm nurse for goodness sakes!"  So, we figured it out and all went well from there. Even Paul started giving Ellie her meds through her NG tube. It's amazing what you learn on this journey. I can safely say that pushing meds through an NG tube was NOT on his skill set prior to this! Anyway, after getting the medication thing down, everything went really nicely at home and Ellie really enjoyed lots if Annabelle time, catching up with her bestie and getting some fresh air and an outing for ice cream down at La Perouse.[...]

We finally have some good news, in fact, some GREAT news. Ellie has achieved morphological remission!
 
Morphological remission is achieved when there is no trace of leukaemia blasts within a small sample of bone marrow containing around 20 cells after a manual count. This was conducted last week and we were informed that Ellie had technically achieved morphological remission on 19 March. Additionally, one of the benefits of enrolling in the MyeChild Trial is that we gain access to Minimal Residual Disease (MRD) testing. This is the newest technology, which although has been around for a number of years, has not been readily available for AML patients. MRD testing takes a sample of 100,000 cells and definitively determines the presence of leukaemia blasts. During this testing, there was no presence of leukaemia in Ellie’s sample. There were less than 5% blasts in her bone marrow sample (normal rate for healthy people) and none were cancerous. We received the results of MRD testing on 24 March and it means that chemotherapy treatment has worked and has eradicated the cancer!
 
This is fantastic news, and the best possible news we could hope for at this critical milestone. However, for clarity, Ellie is not yet cured of cancer and she is not yet in Complete Remission. There is a long way to go in her treatment and she must complete the full four cycles of chemotherapy over the six-month(+) period. MRD testing will be conducted a number of times during her treatment to confirm eradication of the leukaemia. To meet the requirements of Complete Remission, there are a number of other complex factors including CNS, specific analysis of blasts, neutrophil and platelet count requirements, and time-based factors. These will be determined much later and after Ellie’s treatment is complete.
 
This information comes as a big sigh of relief because the last 7 weeks has been very tough on Ellie. Even in the context of Leukaemia, Ellie has had a very rough time. She has been so sick – the sickest child on the ward from what we have seen (but also the only AML patient). While the nurses have not used those words, it is clear to us when speaking with them in the last week or so, that they were really, very concerned about Ellie’s response to treatment. For around five solid weeks she was constantly febrile, constantly nauseated, vomiting a dozen times daily, had a horrendous angry rash from neck to toe (unknown cause), zero counts on neutrophils, platelets, and white cells, and required blood transfusions every other day. We were never certain what the bottom of the trough in terms of toxicity would look like. Every time there was a new complication, we thought she had found the bottom, only to go deeper. She eventually found the bottom of that trough and then sat there for a long time until her lungs began failing and she was admitted to the ICU for 3 days. However, after stabilising in ICU, she started to bounce back, her rash subsided, her neutrophils and platelets began regenerating, and her mood and energy levels climbed.
 
Ellie bounced back so well that she was released from hospital on Sunday 21 March for 5 hours and was allowed to come home, disconnected from her central-line medications (a benefit of living so close to the hospital). Those 5 hours were so good for her morale and mental health (and ours). When we returned to the hospital, her blood counts continued to improve. Due to her improving condition and while we waited for the MRD results to return, our team of doctors made the unexpected decision that she could come home for 7-9 days until we were ready to commence phase 2 of chemotherapy. This took us all by surprise however, the doctors felt it was safe for her to be home (but so close to the hospital) and the mental health benefits outweighed the risks. Ellie has been home since 22 March and we expect she will remain home until 31 March when we commence phase 2 of chemotherapy. In the 72 hours since being home, her condition has improved considerably. She is eating, drinking, talking, laughing, playing, and doing school work – almost none of which, has been achievable in the last 6 weeks. It has been so wonderful having the whole family in the house at the same time, again, something that has not been possible for the last 6 weeks, with one parent staying with Ellie in the hospital at any given time.
 
At this point in Ellie’s treatment, it is impossible to tell whether some of the critical decisions we made in the first 72 hours were the right decisions – particularly regarding enrolling in the MyeChild Trial. This is something we think about every day. Has Ellie achieved morphological remission because of the Gemtuzumab trial drug? Would Ellie have achieved morphological remission without Gemtuzumab? Will the inclusion of Gemtuzumab mean that Ellie will remain in remission and achieve Complete Remission? Will it prevent her from relapsing or needing a bone marrow transplant? Could Complete Remission be achieved without Gemtuzumab? Was the length and depth of toxicity affected by our decision to treat Ellie with Gemtuzumab? Was her toxicity trough so deep because of our decision? Would her lungs have failed and would she have been admitted to ICU if she wasn’t treated with Gemtuzumab? Was the inclusion of Gemtuzumab unnecessary given her Inv(16) AML subset, thus unnecessarily exposing her to increased toxicity and increasing the risk of long term problems in her lungs, heart, and kidneys, which struggled the most during phase 1? We will never know the answer to many of these questions, however I’m confident our decisions were well-informed and were the best decisions to be made at the time; we just hope they were the right decisions and will lead to a good long term prognosis and Ellie’s enduring good health.
 
PC[...]

Ellie is 5 days post ICU and everyone is thrilled with her recovery. Her rash has drastically improved first and foremost! Her white blood cells continue to rise and her neutrophils continue to improve but in a slow up and down trend. Platelets continue to vary. She has a nasogastric (NG)  tube in and continues to adapt to that. The aim is to get off of the TPN (IV food) and only be fed through the NG tube plus any oral intake that she can tolerate. (Side note: Auntie Jen got her to eat 3/4 of a spring roll last night!). The team have dropped her antibiotic and will be dropping the fentanyl PCA soon. They are also aiming to change some of the meds from IV to oral in preparation of going home for a few days, when she is ready! Not yet, but we have it in our sights.  

Her hair loss continues and we may start to try a few cute head scarves or little wraps. I’m buying all sorts of options but it’s entirely up to her with what she feels comfortable wearing...maybe nothing at all. 

Ellie is doing GREAT with her mouth care and Paul, Jen and I are very proud of her. She understands the importance of it now as we have showed her before and after pictures. She does it 3 times a day. She’s also able to get up and walk small distances, like to the bathroom, and we are encouraging her to keep it going. [...]