There are two big events coming up in my diary, coincidentally both on or around the same day. One is the start of the World Cup – come on England! (odds are not looking good though) and the other date, more importantly, is Fabian’s T-Day – come on you chimeric antigen receptor T cells! (slightly longer odds at around one million to one). I jest, of course, as the figures are misleading. Those of you who recall my ‘one shall rout a thousand’ analogy last time, know that even a few million of these killer cells will destroy a billion or more leukaemic ones. In my last post, I mentioned Fabian having had another aspirate to check disease level. This turned out to be 25% lower than the previous reading (around 6 cells per thousand) so we are thankful he is still chemo sensitive. It’s not quite where we wanted to be as it represents a high MRD level but we’ll take any positives. He also continues to remain asymptomatic and in reasonable health although requiring regular platelet and Hb infusions. His last was 500ml and took 5 hours to infuse! Staring at the drip line for that long felt worse than watching paint dry. We’ve now begun the individually-tailored protocol leading up to T day; this has meant a number of baseline tests and starting an intense chemo cocktail designed to deplete his lymphocyte count to ‘make space’ for the modified cells. So it’s back to hospital later this week to stay up to, and for a short while after the big event. It’s almost a year to the day since Fabian’s transplant so it will be a bitter sweet anniversary to be back in isolation on Fox ward. By way of a send off, parents and pupils at his school had generously contributed to buy him a top of the range Lego kit, something that will give hours of pleasure to our master builder.
We’re probably facing the last stop in terms of treatment on this epic journey. There will be no further therapy trials offered if this one fails. One can only remain sanguine when reflecting on this, but the clinical facts can be downright depressing, if truth be told. Yet the biblical example of Job is a huge aspiration to us. On hearing the worst conceivable news, he never blamed God but instead, worshipped Him. Albeit he argued with Him later on and I have to confess to having had a few moans myself, but we do continue to lean on God and the support of others. Will update you all next week.
Another milestone passed as we completed our brief return for treatment at the Marsden and head back once again to the more illustrious environment at Great Ormond Street. I don’t know that we have a preference – each hospital has their pros and cons – but both unequivocally offer a fantastic level of expertise, care and support.
The radiotherapy completed with glowing results (sorry, couldn’t resist that) and the tumour caused by relapse appears to have been destroyed. Today, Fabian had a bone marrow aspirate and intrathecal chemotherapy and the result will tell us how his disease has responded to the low level chemo protocol over the last two months. As they administered the anaestheia, he chirpily drifted into unconsciousness, reminding us he was ‘off to have a kip’. We used to find this moment quite emotional but the cheer repetitiveness of this procedure has anaesthatised us against anxiety. The modified T cells are a little delayed and are not now planned for infusion until early June. We understand the new vaccination approach they will use is now standard procedure on the international trial and this change was confirmed by what was learnt from treating Fabian. We therefore feel that far from being a ‘guinea pig’, Fabian is in fact a pioneer, in the forefront of immunotherapy treatment. He of course, does not quite see it that way but we and many others are immensely proud that he has stayed the distance and kept his spirits intact.
Many of you will have read the recent media attention surrounding Stephen Sutton, another young man fighting life-threatening cancer and the image of him giving a thumbs-up generated a huge fund-raising response across the world. That gesture is a powerful, yet simple symbol of inner strength and one which Fabian has always used himself. So do join us by giving him a big thumbs up wherever you are reading this – and send us a selfie if you dare!
It’s not every day you have to manage two of your children that have conflicting appointments in different hospitals . Today was however, such a day with Fabian needing his daily radiotherapy at the Marsden whilst Cassia needed to be at St Marys for her own follow-up. It has already been ‘one of those weeks’ that has comprised long days spent in daycare waiting on drugs, transfusions or consultations. At times, it seems the coordination of our medical world would keep an administrator fully employed. It is tiring. We have to keep the outcome in sight as we attend daily with Fabian for his treatment and I’m pleased to say the radiotherapy is visibly reducing the leukaemic lump.
We now have dates for the T cell therapy and our T Day will be later in May. This requires a short stay in Great Ormond Street for a course of chemo and follow up observation. We’ve been told that the lab in Nantes has generated a decent sized genetically modified sample so it augers well and the vaccine approach this time should make the difference between success and failure. I recently attended a cancer research conference and there is huge optimism around achieving a cure for certain blood cancers within a matter of years. Fabian’s therapy is just one of a new breed of personalised medicine therapies that have become possible since the mapping of the human genome and enabled scientists to identify the specific genetic mutations of an individual’s cancer. One could argue there has never been a better time to be diagnosed! We’re therefore keeping positive for Fabian’s outcome, against the clinical odds. His courage and fortitude persist beyond his years, whether it is having a deep intramuscular injection into his thigh or having to lay naked whilst nurses prepare him for radiotherapy; seeing his hair fall out (for the third time) seems par for the course for him. Keep standing with us.
I’ve been waiting for something positive to post and today we actually received some positive news – that the particular strain of Fabian’s leukaemia is still positive. Feeling confused? Well, biomedical devotees of this blog may recall that each leukaemia is identifiable by a protein marker which in Fabian’s case is known as CD19 +ve. This information is vital to the efficacy of the immunotherapy as the T cells are engineered to only recognise that marker and the real fear was that following the failure of the first T cell infusion, the disease may have mutated into CD19-ve (cancers have a habit of being remarkably clever when resisting attack). Thankfully then, this is not the case and this means it is full steam ahead with the new batch of T cells next month (cue loud applause). The recent biopsy though, did sadly confirm the lump was cancerous. The most effective, if horrendous, treatment for this is radiotherapy and this is set to start straight after Easter on a daily basis for two weeks. Because it is localised, Fabian will have to have a lead apron shaped around the area to protect other vital organs. He’s also back on a low regimen chemo protocol just to keep disease levels in check. As anticipated, this is knocking his blood counts for six so we’re back to our old friend neutropaenia rearing its annoying head.
People always want to know how Fabian is coping and my answer is always to say better than expected. I’m honestly in awe of his mental toughness to keep going despite the seemingly endless hospital trips and treatment and the perpetual inconvenience of having intravenous lines and blood tests. Most of all, I know he is not afraid even when all of us who know and love him are. Please, if you can, pray that the side effects are minimal and that the disease is held at MRD level.
The Book of Ecclesiastes speaks of the different times and seasons in our lives and declares, ‘He has made all things beautiful in its time’ Ecc 3:11. This is an encouragement, even though events seem far from beautiful right now. At the time of my last entry we had hoped the rising MRD disease level would stabilise, not least because MRD research tells us there was a 28% statistical chance of that happening. The trouble with stats is that that is all they are. So when we learnt that last weeks bone marrow aspirate has confirmed a further tenfold rise in leukaemic levels, we’re reminded that hope is not measured in percentages. At the same time as that operation, we found Fabian had developed a suspicious lump. Doctors immediately scanned this by ultrasound as it was felt this was due to a localised relapse, even though he has not quite reached ‘frank relapse’ in his marrow. Since leukaemia is systemic, rather than metastatic, it doesn’t matter where the disease shows up, it will end up everywhere. We therefore have to accept this state of affairs and proceed as best we can in continued faith and further treatment. The immediate need is to establish the cause of the lump, so Fabian will have a biopsy performed on it as soon as practicable, together with a lumbar puncture to check the spinal fluid for disease and an intrathecal chemo injection into the CNS for good measure. If the biopsy confirms it is leukaemic, they will use radiotherapy targeted at the area. This could mean daily hospital trips for two weeks. We’ve also agreed a plan to start him on maintenance level chemotherapy so as to slow the marrow disease growth long enough until the modified T cells are ready. Cassia gave her blood for these last week – indeed more than twice the anticipated amount so that nothing is left to chance in terms of generating sufficient cells. She is truly a saviour sister to donate more life-giving blood to her brother and remains most humble, not seeking any attention because of this for herself. We returned to the Marsden to reacquaint ourselves with our original consultant who will now oversee Fabian’s treatment up until the T cells are ready sometime in May. Many memories flooded back. Fabian is an old warhorse to the staff there though it is a strange irony to be greeted with the welcome ‘nice to see you back, Fabian’.
Returning to my times and seasons theme, I believe this is a time to pray and not give up. The parable of the persistent widow tells us ‘that at all times we should pray and not to lose heart’ Luke 18:1. We are so grateful for those of you that do. Following the mysterious pastor episode (see previous entry), I also received prayer on behalf of Fabian from Dr Randy Clark, renown for his healing ministry and one- time minister during the Toronto outpouring. God is no respecter of persons – even the dogs eat the crumbs from the table (Matt 7:28). Fabian himself remains sanguine, despite all. He has hopes and dreams to fulfil , so Lego Master Builders, watch out!
Facing a panel of experts on the hospital ethics committee was tough, but reassuring. We met with them the other day to debate the rights and wrongs of putting Fabian through, yet more, experimental therapy. As parents, we had to argue on his behalf our personal conviction that further treatment is both ethical and justified. We also spoke on behalf of his 3 siblings, whose voice also needed to be heard as they have carried much unspoken pain these last 8 years. Our excellent consultant made a strong clinical case for the new science he is proposing. In fact Fabian is spearheading a whole new approach in the type of immunotherapy that future leukaemia sufferers will receive. Less than two years ago, none of these options would be available to us, so whilst being hugely grateful for what we have, there is also the sense that in a few years time, even more advances will have been made that increase curative outcomes. We’ve yet to receive the panel’s recommendation but their initial feedback was that the burden of treatment does not outweigh the benefit and that it would be appropriate to proceed. This gives us great reassurance that we are all doing what is best for Fabian and our family so now we are ready to press on.
Later that day, he was due to have a marrow aspirate to check the level of disease – vital to see what is going on. But it was not to be. Just shortly before going to theatre, he sneakily found a couple of biscuits and munched them down, instantly rendering an anaesthetic too dangerous. Try making a 12 year old fast all day – not easy! It was also a shame because they had planned to remove his gastrostomic tube which has become a real nuisance. Fabian is concerned that once removed, the resulting hole in his stomach will make him look like he’s been shot.. Cassia will donate her blood next week and that will be sent to the lab for modification. At this stage, no-one knows if it will be needed but the process takes two months to complete so needs to get started.
On the 2nd March we celebrated Fabian’s 12th birthday. Many of his friends came for the party which began with a trip to watch the Lego movie, a truly rollercoaster film. Back home, we received an unannounced visit from a Korean pastor who had come to pray for Fabian’ healing. It was truly moving as children and parents all crowded into the lounge to join together in prayer and God definitely turned up for the party!
This entry has been a difficult one for me to post. Our fight against leukaemia, analogous to an epic tennis match, has gone to a tiebreak just when we thought we might go a set up. In reality, I’m sorry to report the latest MRD level is not lower, or even the same as the previous two readings but has in fact risen tenfold. We are still talking low molecular levels but nevertheless this is a blow to our rising optimism. It would appear that the precious T cells have simply dispersed and no longer show up in the cell flow cytometry. The reason for this is not yet understood but in part seems to be because of a lack of EBV, the body’s naturally-occurring virus that triggers lymphocyte reproduction. It was always one of the known uncertainties going into the trial but at least the evidence proves the modified cells worked wonders whilst they were still present.
This unwelcome turn of events presents yet another clinical decision to make on Fabian’s behalf – should we repeat the process? Well, yes and no. To paraphrase Einstein, there is no point repeating the same things and expecting a different result. But the recognition of the importance of EBV means that the next time around the team would infuse the T cells together with an artificial EBV vaccine, hopefully ensuring they persist for longer. This has never been attempted anywhere worldwide. There are, however, several immune-related factors that could inhibit this and rather perversely, we would have to wait for the disease to progress to full relapse before doctors can determine whether these factors would negate repeating the T cells.
As I write, our feeling is to proceed with harvesting more of Cassia’s T cells to begin the modification process in the event that they may be needed later on should disease levels rise. This means we’ll need to leave the CD19 trial and therefore ongoing treatment cannot be met from the research funds. Furthermore, the hospital ethics committee will need to clear this experimental treatment and Cassia requires hospital approval to donate for a third time. Neither she or Fabian should be used as guinea pigs! We also know that the American version of this treatment has achieved better success and that it could become available, probably in Germany within a year. The possibility of accessing this in the U.S. is worth exploring but other non Americans have tried and been turned down and in any event, it would be prohibitively expensive.
And yet new research on MRD outcomes shows that at least a third of children with the same level of disease as Fabian don’t relapse and go on to enjoy a good quality of life for many years. Since he has been such a fighter, Fabian has every chance of being the one in three. The next BMA will tell us more. Meanwhile, we feel more dependent on God than ever to work a miracle. It may come through T cells or divine intervention, we don’t mind. New balls and new hope please..
Happy new year to all our faith4fabian followers!
The analogy of a tennis match comes to mind – hence the title – as I report to you the wonderful news that Fabian’s second bone marrow aspirate since the T cell infusion showed no increase in MRD, following the significant drop last time. This is perhaps more meaningful than the previous reading as it confirms that immunotherapy alone is destroying and holding back the cancer. In research terms, I guess this is the best outcome the clinical trial team could have hoped for and certainly our talismanic consultant is elated with Fabian’s progress. The nervous waiting and wondering between each aspirate result, though, is emotionally exhausting, so upon hearing it, we didn’t leap for joy with whoops of delight but simply felt like a huge internal burden had been lifted at least for another month. A relief too, for the other children. Oli is back at Uni now but a great boost for her as she faces some tough biomedical exams. Doctors remain unsure as to the durability of the T cells; a key indicator of this will be continued absence of B cells leading to a low immunoglobulin level, though that can be replaced artificially. Somehow I wished I’d paid more attention to haemotology at school..
So back to my tennis analogy, it feels like this going to be a five setter with leukaemia having taken the first two sets (through relapse) but prayer and treatment now leveling the match and despite all the rain we’ve had, it hasn’t delayed play!
The dogged film crew remain on hand to capture every key moment. Hours spent waiting for an expected call from our consultant are par for the course. Here is Fabian posing with some of their impressive camera equipment.
My last entry for 2013 rounds off what can best be described as a year of ups and downs but thankfully ending on an ‘up’. Not that I’m superstitious, but Fabian has only relapsed on odd numbered years – 2011 and 2013 – so 2014 bodes well.
A couple of weeks ago I reported that the first aspirate since T Day showed a significant drop in leukaemic levels and that can only be attributed to the effectiveness of the immunotherapy treatment. A single reading, of course, does not constitute a downward trend so the next aspirate reading mid January will give us enough data to plot a line graph which we hope will confirm this. Meanwhile, we have learnt that the all-important EBV virus which had apparently disappeared was found to be present again so more cause for celebration. Fabian himself continues his run of good health and his fragile immune system is starting to strengthen. A further dose of Cassia’s stem cells may be required if his blood counts don’t pick up over time.
Christmas has been somewhat uneventful with the dreadful weather limiting much outdoor activity or trips. Having received a number of gifts on his present hit list, Fabian claimed it was the best Christmas ever. Not sure his siblings agree, now that they are being peppered with foam darts from his new semi-automatic nerf gun! Time then to recharge and all face 2014 together, whatever it plans to throw at us. Bring it on!
Consultants choose their words carefully and they are certainly not prone to outbursts of emotion. So when ours called last night with the results of Fabian’s most recent BMA and said he was cautiously optimistic we knew it was indeed good news. It has been a month since T Day and this BMA result would be the first – and most important – indicator of whether immunotherapy had worked. We knew the T cells had multiplied, thankfully because of the presence of EBV virus, since the original infusion had been so small and may not have been sufficient to overcome the disease which the last test had confirmed was already returning. Furthermore, Fabian is still struggling to maintain his blood counts due to the tenuous bone marrow engraftment. Last weekend he was close to being neutropaenic and anaemic and required both platelet and Hb transfusions plus GCSF to stimulate white blood production. However, the BMA result showed a zero reading against one marker and reduction of half in the other.. This is unequivocal proof that the leukaemia has been significantly reduced and one can assume that extrapolating this forward he will be disease-free within days or weeks! More importantly for the clinical trial, this has been achieved without the use of drugs. Caution, though, tells me to hold fire on a mega-rave celebration just yet.. We were also told that an unintended consequence has been the loss of all remaining EBV so the concern is that those precious T cells will remain in his body, without which Fabian will have no continued protection. We’ll know more after clinic this week.
So I guess the words ‘joyful Christmas’ take on new meaning for us now. It is truly the best present, other than the true reason for the season. With Christmas approaching, Fabian is looking forward to big sister Oleander coming home from Uni tomorrow and his present list reads like the Argos catalogue. Even the likelihood of family squabbles over the holiday period seems inconsequential compared to the value of togetherness.