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.[...]