It’s been a rough couple of weeks for poor Ellie. She’s really feeling the effects of the chemotherapy this time around. She recently finished a five-day course of high dose Fludarabine and Cytarabine (FLA) and her counts have almost hit the bottom of the trough. She has been febrile for over a week and very symptomatic. Her most obvious symptoms are constant nausea (though thankfully not much vomiting), chemical conjunctivitis (caused by high dose cytarabine), and fatigue. She is also retaining a lot of fluid, particularly in her face which is very swollen, especially on the right side where her right eye is almost swollen shut. When Ellie is feeling these effects she starts to shut down, so she’s largely been non-verbal, and when she is verbal, it’s not pleasant! I don’t blame her though; I would be the same if I was that sick.
 
Given Ellie’s constant fever, the team was concerned that she had another infection. However, after four tests, nothing has grown on the blood cultures, so they have now tested for a viral infection, but we likely won’t see the results for a couple more days. We think it’s unlikely she has a viral infection and is more likely to just be the effects of the cytarabine.
 
It’s a fine balance to determine how much chemotherapy to administer in relapsed AML. I have previously said that the treatment plan in 2021 was all per the MyeChild protocol so we were well prepared. After relapse, there isn’t a set protocol and its dependent on the individual and how they respond. When the team told us the plan for one round of FLA(G) and then maybe a round of FLA, we questioned why they weren’t planning on stronger options to ensure Ellie stays in remission. It was explained that last year she was essentially given as much chemo as the human body can handle which is much more than adults are given. Now she needs more. So, it’s a challenge to find the balance – just enough to achieve remission, but no more to reduce the risk of significant long-term issues. The cumulative effect of chemo is now obvious to us given Ellie’s reaction to FLA when she handled it quite well in the last two phases of consolidation therapy last year.  
 
We still don’t know a lot about the bone marrow transplant however, we should have a meeting with the donor team soon. The head oncologist indicated that we have a ‘cord donor’ lined up for Ellie which is great news. Stem cells taken from an umbilical cord reproduce into mature, functioning blood cells quicker and more efficiently than stem cells taken from the bone marrow of a donor. This is reassuring given none of us (immediately family) were suitable matches for donating bone marrow.
 
This is a useful link to understand the basics of bone marrow transplant: https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/bone-marrow-transplantation
 
We have lots of questions for the donor team and transplant team, and are anxious to know more. However, as our team keep telling us – one step at a time.  
 
PC[...]

We finally have some good news to share: The results from Ellie’s Bone Marrow Aspiration (BMA) confirms there is no identifiable presence of AML cells. This means she has achieved morphological remission after the first round of chemotherapy since her relapse.
 
This is great news and a sigh of relief for us as we know that remission status immediately prior to bone marrow transplant (BMT) is an important prognostic indicator. We also knew that it would be more difficult to achieve remission after relapse compared to first diagnosis.
 
We have been quite anxious over the last week because the BMA was conducted when Ellie’s bloods were ‘borderline’ for the test, meaning the medical team were taking some risk conducting the BMA last week instead of waiting for her counts to recover more. This risk was taken because it is important to get moving with the next course of chemotherapy and Ellie’s bloods were a little slow to recover. If the sample wasn’t good enough, she would have to repeat the BMA to gain a better sample which could be tested more accurately.
 
We were told after the preliminary results of the BMA that the team ‘thinks’ the sample is good but also that it showed a 2.6% cluster of suspicious cells. These were either AML cells or just immature regenerating healthy cells, which look similar under the microscope in the manual laboratory count. We had to wait for the Flow Cytometry testing to confirm. We were also anxious as Flow Cytometry is not as sensitive as PCR which is how they tested last time when Ellie was on the MyeChild clinical trial (Flow up to 1:100,000 vice PCR 1:1,000,000). It is still not entirely clear to us why Flow is used over PCR however, the literature shows Flow is much more common/applicable and there is no clear ‘standard’ of testing as each test has strengths and weaknesses.
 
On Friday, we received the good news that Flow Cytometry did not find the cytogenetics (inv(16)) characteristic of Ellie’s AML within the cluster of suspicious cells, confirming they ARE immature regenerating cells and therefore declaring Ellie to be in morphological remission.
 
As I have said, this is great news. However, we are finding it difficult not to question every decision and not become cynical. Why not wait to do the BMA later? Why not commence chemo earlier? Why not PCR over Flow? Was the BMA sample really good enough? Exactly what is good enough? Should we repeat the sample? Do we actually have certainty that all of the suspicious cells are healthy? Why are we relying on lack of evidence of inv(16) rather than positive confirmation that every cell in the sample is mature and healthy? These are the questions constantly running through our heads.
 
Nevertheless, we’ll take all the good news we can get, and continue looking for the silver linings.
 
Ellie and Annabelle’s new school – St Andrew’s Catholic Primary School – has already been incredibly supportive. It’s unfortunate that Ellie only just completed Term 1 in her new school before relapsing. However, a number of parents have been so generous and thoughtful to reach out for support. From helping with school drop-off/pick-up for Annabelle; looking after Annabelle at school; establishing a meal-train which was shared across the whole school; and teachers who have gone out of their way to include Ellie through Zoom and online learning – we feel very fortunate to be part of such a supportive community.
 
We have also been lucky to have Ellie home while her bloods have been recovering. It’s so good having her here – for her mental health and for Annabelle to be able to play with her sister again. We’ve been taking Ellie to hospital regularly for lumber punctures and intrathecal chemotherapy but she’s handling the disruption very well. After around six lumbar punctures this course (10 if you count the ones that didn’t work), Ellie’s cerebral spinal fluid (CSF) is now clear of AML cells. It is also believed (but not confirmed) that the AML in her brain has been cleared. There’s really no way of knowing this until she has another MRI in a couple of weeks to see if the chloroma has dissipated. At this stage, there’s no talk of biopsy or other brain surgery however, that will all depend on the outcome of the MRI.
 
While there are no longer detectable AML cells in Ellie’s bone marrow and CSF, it doesn’t change the plan for her treatment. Next week she will commence course two of high dose chemotherapy, followed by bone marrow transplant, likely in about 4-6 weeks. We still don’t have much information about the BMT and are hoping more info will come next week.
 
For now, we’re enjoying having Ellie home for the last couple of days, continuing to think positive thoughts, and searching for the silver linings in every situation.
 
PC[...]