Phase 2 Milestones

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