June 17, 2015

Hanging on to hope

I ask Margot to repeat after me “I love you”. She replies “apple juice”.

I asked Margot to repeat after me “I love you”. She replied “apple juice”.

In telling Margot’s story, I regularly look back through my journal to see where we were this time last year. Having learned that she had relapsed on 13 June 2014 and then reflected over that weekend, Vicki & I picked up with the doctors at Great Ormond Street Hospital (GOSH) again to ensure that we understood where we were and what the options looked like for Margot.

We were still very much seeking a curative approach at the time, although there were increasingly fewer options open to us and the ones were were discussing were starting to sound more and more tenuous.

Essentially, we needed graft versus host disease (GVHD) to occur, enough to trigger graft versus leukaemia (GVL), but not too much so as to become life threatening to Margot, nor to cause other issues and lasting damage to her.

As I say, it was getting pretty tenuous.

I wrote the following about hope after considering the advice from the consultants at the time. Part of the reason for feeling that there was still hope for Margot was our discovery at the time of a new treatment called CAR T-cell therapy. It wasn’t a drug as such, but was instead gene therapy.

And just last week, almost a year on to the day, I received a call from an old friend called Frank, who told me that his partner Matilda is currently undergoing CAR T-cell therapy for her ALL, with fantastic results. Really great to hear.

Wishing you continued success with the treatment Matilda !


Team Margot

Together, saving lives


17 June 2014 – Hope

Having slept on things for a couple of days, my emotions are calming down and yet in a way, it still feels quite like the awful situation we faced back in October when Margot arrived in intensive care. Storm clouds rolling in fast and lots of uncertainty.

Mercifully, the rash doesn’t appear to be bothering Margot at this stage & she isn’t wanting to itch / scratch

Mercifully, the rash didn’t appear to be bothering Margot – she wasn’t wanting to itch / scratch

Margot was showing some signs of GVHD on her skin - but the question was whether the rash / reaction was sufficient to cause GVL

Margot was showing some signs of GVHD on her skin – but the question was whether the rash / reaction was sufficient to cause GVL

The conversation with Dr Robert yesterday really didn’t instill us with much confidence in the likely options available, if the GVL (Graft versus Leukaemia) doesn’t work. The options he discussed didn’t appear to offer anything more than a slim chance of success – we do appear to be at the wrong end of the risk spectrum. We are hanging on to hope.

The basic plan is for Vicki and I to try and hold firm; all the while we feel as though we’re standing on the edge and staring down into the ‘precipice of panic’. We haven’t mentioned any of this latest news to the boys and will hold off from doing so, at least until we have a better grasp of what’s actually going on and what we might be able to do about it.

I am trying to move through the emotional / totally helpless phase a bit quicker this time around; I have just about stopped spontaneously welling up and feel like I have begun the data logical fight back.

Back in April my father sent me a link to an experimental treatment in Philadelphia for relapse patients; it wasn’t relevant at the time but then last night, totally independently Luisa H flagged the same treatment with me.

This experimental approach treats the relapse of acute lymphoblastic leukaemia (ALL) after transplant by genetically modifying T-cells to recognise CD19 on the surface of leukaemic cells so that they can then kill the leukaemic cells (as well as normal B-cells). GOSH happen to have a similar study running, though in their study they use a somewhat simpler receptor so their results to date haven’t been as impressive as those in Philadelphia. Even in the Philadelphia study, it’s important to remember follow up is short so we are not certain whether patients are truly cured yet.

Regardless, this is another avenue for us to explore and I have spent much of today seeking to establish whether it might be a relevant and appropriate treatment for Margot.

Professor Amrolia explains that the difficulty in Margot’s case is that she has 2 components to her leukaemia. The lymphoid (ALL) component expressed CD19 at initial presentation (which is necessary for this treatment to work) but the majority of leukaemic cells in the myeloid component (AML) did not. While at present the evidence of early relapse is in the ALL (lymphoid clone, which remains CD19+ve), the concern would be that if we treated with this approach we would not target the myeloid leukaemic blasts which don’t express CD19, so even if the approach worked Margot might progress to CD19 negative relapse of the myeloid component. Apparently, Philadelphia have seen this in a couple of cases of ALL where not all the cells expressed CD19.

Regardless, it’s now on the agenda for discussion with the Haematology team on Thursday (it wasn’t one of the options mentioned by Dr Robert yesterday), after which the Professor will get back to us. In the meantime, he says that it is probably sensible to hold off the Rituximab (meds to combat the EBV virus Margot has) until we decide what we are doing.

In response to my questioning, Professor Amrolia also confirms that this is the original ALL clone returning – same chromosomes, same MRD profile, same surface markers. He says he is not certain that the myeloid clone (AML) will also come back, but he believes it to be “reasonably likely”. If the AML clone also relapses, this would mean we would have to strike this experimental treatment off our list of options “because Margot’s myeloid clone does not really express CD19 and therefore won’t be targeted by this approach.”

Assuming the CD19 CAR T-cell therapy DOES work it will delete both leukaemic and normal B-cells so potentially this will render Margot susceptible to infection by reducing the production of immunoglobulins from normal B-cells. In view of this, in both GOSH and Philadelphia studies, they monitor the immunoglobulins after treatment and give replacement immunoglobulin (by IV every 3 weeks) to prevent infections. How long you need to do this depends on how long the gene modified T-cells persist. GOSH believe this is an acceptable toxicity, if the alternative is relapse.

To comply with the GOSH study, Margot would need to go through a 2nd transplant, which the Professor describes as a pretty major undertaking. My cousin Mazen (an oncologist in the USA) is seeking to establish whether Margot might be eligible for the Philadelphia study (which wouldn’t require a 2nd transplant).

Interestingly, Mazen has emphasised that this latest MRD test may or MAY NOT be meaningful. He explains: we have learned over the last decade that cancer has hierarchy similar to every other tissue – this means that not every cell is actually capable of causing a problem, but only the small percentage of what is called cancer stem cells. Accordingly, a molecular test may detect ‘a component’ of leukemia but it cannot determine the type of these remaining cells – stem or not.

In other words, as far as he knows today, there is no assay or test to distinguish these possibilities and only time will tell. If this component is more prominent/represented over time, then it is a real concern. Otherwise, it may simply be a useless group of cells that will extinguish over time. Inshallah.

And for now, that’s really good to know – it might just help make the existing period of limbo that little bit more bearable and is another bit of hope for us to cling on to.

Husband to Vicki and father to Oscar (2007), Rufus (2008), Digby (2015), Humphrey (2017) & Margot (2012-2014)

Posted in: Journal