On 19 December last year, Vicki & I had a meeting with Margot’s bone marrow transplant consultant at Great Ormond Street Hospital.
What follows are excerpts from the notes I took at the time.
The consultant wanted to meet & discuss:
• What had happened with Margot – he had already read her file but wanted to hear from us directly
• Why transplant is a reasonable thing to do
• What it involves
• Short term side effects
We have had this meeting booked in the diary for over a week now however as yet, we do not have a confirmed donor. So this meeting is all about what we hope will be possible for Margot, in the event that we are fortunate enough to find a suitable donor.
Right upfront, the consultant declares: “I will be straight with you, but some of this is not going to be easy to hear”.
[Good. I feel ready for this. And frankly, I feel like we have heard it all before. This can’t hurt me. I’m in typing mode taking notes. This is a clinical exercise. He says that we have a decision to make. OK ! C’mon, let’s go.]
He goes on: “It’s difficult to provide you with likely outcomes because there’s so little data on this sort of dual lineage leukaemia in infants. There are some situations when it’s really cut and dried, but in Margot’s case, there isn’t enough data to tell you anything with certainty.
I have read the doctors notes, but tell me as parents: When did you realise something wasn’t right ?”
We relate our story. Before. What happened. And since our arrival. My notes actually came in handy and I was able to refer back to times when, anecdotally / from memory Vicki & I were factually inaccurate.
He listens and explains that he wants to physically examine Margot later today.
“Margot has a nasty form of leukaemia. Most children are curable with chemotherapy alone. Regarding dual lineage, they tend not to do very well with chemo. Most patients on record have relapsed with chemotherapy treatment alone. More globally : the outcomes of patients with this same dual lineage are poor.”
[Yup. Heard all that before.]
He refers to Margot’s Chromosome t4:11 and explains that as far as they know, children with this Chromosome PLUS AML “is a bad factor.” There’s a higher risk of relapse.
He explains what normally happens with AML patients is that they tend to get transplants at first remission: “So if Margot had straight AML we’d transplant her on the basis of chromosomes alone.”
“Dual lineage outcome with chemotherapy alone is poor, there is a 60-70% relapse if chemo alone is administered.
“The danger is, if you decide to go that route and Margot relapses a year from now, will we be able to get her back into remission ? If we were successful in doing so, we could always do a transplant at that stage. But she could get very sick very quickly again and the question remains: could we get her back into remission ?”
[OK – I get it. In fact, the haematology team have said all along that the best chance of Margot being cured is for a bone marrow transplant. They have been clear and managed our expectations on this being the most likely course of action and right from the outset. I find myself saying this out loud. For some reason, I think I am giving Vicki some sense of reassurance.]
“So, given the high chance of disease returning, how to prevent it ? The only thing we can do is a transplant.”
“Much higher doses of chemotherapy are possible under the circumstances of a transplant. Margot’s chemo to date has been at a level where Margot’s bone marrow will recover.
Donor transplants work in 2 ways:
[Hearing him say the words “lethal dose” throws me completely. I flick back through the notes I’m typing and it dawns on me that the chemotherapy treatment Margot has received to date has in contrast been relatively gentle. That hits me quite hard. I’m suddenly flummoxed.]
By the time I regain my composure, the professor has moved on to the likely timing and more practical matters. He is speaking about needing a donor transplant in February. Margot will need a further course of chemotherapy before then. “She will probably move into Fox Ward for 8 weeks…”
The professor explains what Margot will need:
A Double lumen Hickman (this is a central line into Margot’s chest which has two “access points” permitting two simultaneous transfusions)
Isolation, for probably 3 weeks
Naso Gastric tube
Unique blood and platelet support.
He walks us through the process: “Margot will start with ‘conditioning chemotherapy’. This is much stronger than what she has been given to date.” The historic ‘Regimen’ is toxic to babies, he explains. So now we are using a new one, which involves 3 chemotherapy drugs plus an antibody proposed:
1.Fludarabin – which he says is very mild
2.Trisolfan – this one is new to us – given over three days introveniously (-6 to -4 days before transplant). It’s a strong chemotherapy that fights against the leukaemia and makes space for the new cells. This makes you vomit. Causes rashes especially in young babies. The rashes tend to blister and get dark – but they get better over time. And this chemotherapy will also contribute to mucositis (this is the blistering of the stomach lining and oesophagus).
3. Thiotipa – this is given 3 days prior to transplant. It also contributes to mucositis and causes rashes. But it helps wipe out the bone marrow.
PLUS an antibody treatment called ATG to prevent the donor cells from attacking Margot too much. It’s a foreign protein, so you can get reactions to it. “But we are used to these side effects and can deal with them…”
We prefer male donors in general. And bone marrow is preferred for Margot, over peripheral blood.
On the day of transplant : Donor gives bone marrow; because we prefer bone marrow, we ask the donor to undergo a general anaesthetic to collect bone marrow directly from their bones (usually their pelvis). If the donor refuses to agree to the bone marrow collection route, we could approach another potential donor and ask them instead.
The donor stem cells are shipped over and because it has come from an adult, we may remove the red blood cells to size it down (it’s for an infant after all). The bone marrow is infused just like blood and the stem cells cleverly find their way via the blood, into the bone. It usually takes 3 weeks for the bone marrow to find it’s way in, settle and start working again producing the right blood cells in the right proportions.
Hence the period of isolation for Margot. ”During that period, Margot is almost certain to get infected. And when she does, we will treat it.”
Then he gets more graphic still:
“Young babies can get quite sick. It is possible that she may experience chest issues… Chemotherapy doesn’t just affect bone marrow, but it affects all cells. She will lose her hair. She will lose the the lining of her gut.”
Regarding feeding: will she tolerate the NG tube? If it is an issue, we could put a “peg” into the stomach. A peg is a line directly into the stomach, through which the patient is fed food, primarily milk. Around a third of patients have a peg.
If we don’t opt for a peg now, can we have one put in after the transplant ?
No. That’s not possible. You need to decide on whether to have the peg in advance.
TPN (Total Parental Nutrition) is another alternative, which involves nutrition injected via the hickman line – but then the stomach isn’t used / working at all and this can create other issues besides.
“Once discharged, she will be on a lot of meds. She will be in pain and will not wish to eat or take meds orally. The meds are difficult to administer without a tube.”
“The meds can have their own side effects. There’s a real risk of kidney impairment. We will try to keep an eye on it, but… ”
I notice that every time the conversation gets into a potentially awkward situation, he professor swiftly moves it along to the next topic of conversation. He is polished. It is obvious that he has done all this many times before.
“Ciclosporin – we use this to prevent graft v host disease (GVHD). It can cause fits and neurological issues. It will also contribute to kidney issues.”
Vicki asks: Are these issues permanent ?
“Mostly, these things get better when you come off the drugs” he replies.
“About 3 weeks after the transplant, we will see the white count coming up and then do some tests.”
What if Margot’s body rejects the donor stem cells ?
“The chance of rejection is incredibly small – less than 5%. If that did happen, she’d be left with empty marrow. Then she would need an emergency 2nd transplant, either from the same donor, or from a parent.”
He goes on: “Almost certainly she will be a 100% donor.”
What’s a 100% donor ?
We don’t want to see any of Margot’s cells there; it means they would have survived the chemotherapy.
At that stage, the gut will begin to heal and her risk of infection will go down. “It will take a while for her lymphocytes to come up again, so she will remain at risk of virus infection. This is the reason why we lose most patients” he says.
Quickly he moves on again: “The bad viruses to look out for are:
EBV, CMV, Adenovirus. They affect the lungs, eyes, liver and glands. They’re all at risk. All these matters are serious if they happen. So we do aim to prevent them and treat before we see any symptoms.
We are also looking out for Graft v host (GVH) – when a donors immune cells see Margot’s are different. Apparently, we may have a potential mismatched donor (a 9 on 10, not a 10 on 10), so typically if there is a mismatch, there is a higher chance of:
the donors immune cells see skin is different: symptom is a rash
the donors immune cells see her stomach is different: symptom is vomiting
the donors immune cells attack her lower gut : symptom is diarrhoea – this will mean she is kept in hospital “for far longer”
the donors immune cells attacks the liver: jaundice.
The latter two are much more difficult to deal with. They could mean that GVHD continues for years. Chronically affected joints, lungs etc. It’s nasty. And the risk is increased by using a mismatched donor.
The outcome / these side effects can be improved if we use bone marrow. That’s why we want to avoid peripheral blood cells and why we prefer bone marrow.
All being well, April could be the earliest time Margot comes home and is treated remotely, post transplant. From now, until April is at least twice as long as we have experienced so far – it feels like a long way away.
Slowly the bad cells will calm down. Then you stop the anti immune suppressant drugs. Probably 3-4 months post transplant. Immunity recovers say 9 months after the transplant.
And then hopefully by the autumn we can pull out the Hickman line.
We do bone marrow aspirates at 1,2,3,4.5,6,9 and 12 months. If you get to a year from transplant (i.e. Feb 2015 in Margot’s case) the chances of cure are very good.
Late effects of transplant – all being well, we get transferred back to haematology. From there to another department as their management becomes more light touch.”
Later on in life, they will watch Margot’s progression through puberty. ”
[Deep breaths. I’m welling up. I try to regain composure and go over the potential options again].
If Margot has Chemotherapy alone – there’s a 60-70% chance of relapse. And then the question is whether we can recover post relapse to achieve remission again and then do a donor transplant ? He makes it sound unlikely.
Transplant – a 10-20% chance of Margot not making it through from transplant related matters.
It is all suddenly very real. And fraught with danger.
“But the supportive care is getting better.”
He summarises: “The chance of relapse is hopefully reduced via more intensive chemotherapy and transplant. But in all honesty, we just don’t know. There just isn’t the data. But if we do this, then we have done everything we can to prevent the disease coming back.
Most doctors will recommend transplant at first remission”, he says. “And that’s our recommendation to you. ”
“You might not get another shot”.
At this point, he tries to sound reassuring: GOSH is the largest transplant outfit within europe & our results are better than our European counterparts and are as good as the results coming out of the USA…
We talk about the next steps for Margot and post bone marrow aspirate tests, what chemotherapy is likely. I ask him whether it matters: on the basis that the transplant conditioning drugs are so severe – why does it matter whether Margot has one type of chemotherapy, as opposed to another, or indeed none at all ?
He replies : “The lower the disease burden going into transplant, the better.”
I have recently read about gene therapy being pioneered in the leukaemia field and understand that it is GOSH leading the way. So I ask him about whether gene therapy is an option for Margot.
The professor explains that there is gene therapy for genetic immune disorders, which is not relevant, but that the gene therapy I am referring to is probably the work that he is personally leading. Apparently, they genetically modify immune cells from the donor and use a virus to put in a gene, to make the T cells see a particular molecule and so they can fight against it. In the case of leukaemia, they are doing this with ALL (Acute Lymphoblastic Leukaemia). And he explains that the difficulty in Margot’s case is that she doesn’t just have ALL alone.
He goes on to say that some of Margot’s AML (Acute Myeloid Leukaemia) cells have ‘cd19′ (around 32% of them) and they are not eligible for study because they are not “a good target” for that kind of gene therapy approach.
Sense check: I take a breath and pause to think for a moment. I’m scared. And emotional. I stop typing and look up at Vicki who is wiping tears from her eyes. The professor offers her a tissue and we thank him for his time. He explains that he wants to give us some literature and nips out to get some reading material for us to take away.
Once he leaves the room, I lose it. I’m thinking about “the decision” we are supposed to make. The brutal reality is that this gentleman is really telling us that there isn’t any decision for us to make. In the absence of any data, the doctors weigh up the risks and go with the most sure footed approach, which in Margot’s case has to be a donor transplant. And all he has really done in this, our first encounter, is to lay the ground work and prepare us for the rough ride ahead.
How are we supposed to prepare poor Margot for this ? How can she possibly begin to understand ?
I think it was the “lethal dose” comment that first triggered my emotions. Margot’s response to chemotherapy has, according to the doctors been good, but we have witnessed her suffer some really nasty reactions along the way.
And the chemotherapy thus far has been “gentle” by comparison to what she faces ??!
Just thinking about this and I break again; I thought I was beyond this ?! I find myself sucking it up and regaining composure just as the professor re-enters the room. He holds out the leaflets in my direction, but I can’t bring myself to take them from him, so Vicki receives and puts them in her bag.
He talks some more but I have now stopped typing and my focus is elsewhere – I can no longer hear what he is saying. My mind is a busy place. Then my thoughts are interrupted and I hear him say “… you all have time together now; so enjoy it. You must enjoy your time with Margot when you take her home on Friday.”
As we leave the consultation room, I think about the fact that we are currently revving up and getting excited about raising awareness and promoting a donor drive and IF we are lucky enough to find a suitable donor for Margot, we have all this to look forward to.
The really upsetting thing to me is that we will need to watch Margot get sick again, before she can get better. So I hold on to the thought that the ultimate end game is her survival and full recovery. And the fact that a bone marrow transplant can potentially deliver that.
We haven’t really done much / been anywhere today, but the whole BMT discussion plus the worry around Margot’s aspirate this morning have left both Vicki and I mentally and physically exhausted.
When we get back to Elephant Ward, Margot is asleep on Grandma Annette’s lap and the training lady is there; she has been waiting for us so that she can show us how the pump works. This is the bit of kit that we need to take home with us so that we can continue to feed Margot via her NG tube.
It’s now around 15:45 and we haven’t eaten lunch. The lady looks at me and realises I’m not in the best of shape and suggests she come back tomorrow. Vicki explains where we have been and apologises for being held up and late – she seems to know that the lady has come to GOSH specifically to train us today, so I head off to the canteen to get some late lunch for us and Annette while Vicki presses on with the training.