CAR-T Therapy – Our Scientific Miracle

The Beginning

I knew something was wrong as soon as I arrived back in the UK after a trip away with friends - I had an urgent message on my phone to call my husband as soon as I landed. That was the start of what the self-help books call our ‘journey’. It transpired that my husband, let’s call him Richard, had been to see the GP while I had been away and needed an urgent blood transfusion the very next day as he was so anaemic.

It took many more months of worry, uncertainty, tests and appointments before we were given the awful diagnosis that Richard had lymphoma – a blood cancer. But he was ‘lucky’, we were told, it was Diffuse Large B-Cell Lymphoma which could be zapped with just a few rounds of chemotherapy.

After a veritable arsenal of treatments at Southmead Hospital and in a very sinister twist, we were told that he was at risk of the lymphoma jumping from his blood system to his central nervous system and his brain. As a precaution, he was required to have chemo chemicals injected directly into his spine at Bristol’s Oncology Centre (BHOC). Little did we know how much time we’d be spending at BHOC over the next year or so.

l remember sitting with Richard that first time in the chemo suite at Southmead while the nurse injected the noxious cocktail of chemotherapy drugs into him, thinking – with tears in my eyes – that this was the start of him being well. But some things are never that easy.

Richard lost his hair and his appetite and his immune system was shot to pieces. He was very vulnerable to infection and we had a number of scary races back to Southmead when Richard had spiky temperatures. There is nothing more desolate than walking through the long concourse in Southmead in the early hours of the morning, when not a soul is about, you haven’t slept or eaten, and you wonder if that will be the last time you see your husband alive. They say that you are always aware of life’s first times and you can recall them from memory; but, sadly, more often than not, you are blissfully unaware of life’s last times.

Despite everyone’s very best efforts, that first round of chemo failed, and the lymphoma came back. In truth it never really went away. Richard and I were stunned.

A Revised Diagnosis

It was around this time that we first heard the consultant use the phrase ‘double hit’ lymphoma – I understand that about 5% of lymphoma cases have this extra mutation to the cells which, unfortunately, puts the disease into a whole new ballpark. 

Richard’s prognosis wasn’t looking good and Southmead decided that it was time to pass us on to the BHOC for our last option - a stem cell transplant – a lifeline! 

All we needed was for him to go into remission long enough for healthy stem cells to be harvested – then they would give him a dose of chemo before transplanting his own cells back. Unfortunately, Richard didn’t even complete the planned course of treatment as a scan showed that the cancer was progressing. It was clear that the lymphoma wasn’t going to give up that easily and he wasn’t going into remission.

Suddenly we were running out of options. We were both scared; our second granddaughter was on her way and Richard was feeling worse each day. On possibly the hottest day of the year, we solemnly met with a solicitor and Richard put his ‘affairs in order’ - believing that he didn’t have long.

A Long Shot?

And then, just a chink of light, Richard’s consultant mentioned CAR-T therapy – a new treatment which had only a few months previously been approved for lymphoma cases where two rounds of chemo had failed. CAR-T (Chimeric Antigen Receptor) therapy works by genetically modifying the patients own T-cells to attack the cancer cells. 

BHOC was one of only a few centres in the UK that was approved to carry it out. But because the treatment was new and extremely costly, each case had to be approved by a national panel. I was terrified that Richard would be considered too old. I was so desperate for him to be accepted for the treatment, that I took a photo from our most recent holiday to our next consultation - Richard and I triumphantly standing in our cold weather gear at the top of a mountain in Patagonia! That consultant held my husband’s life in his hands, and I had to show him that the shell of a man now in his consultant’s room was previously fitter and more active than most men of his age and not that long ago.

After a very nervous wait, we heard the amazing news that Richard had been accepted – we were over the first hurdle! 

A Long Journey

The complex CAR-T process starts with the ‘harvesting’ of T-cells from the patient’s blood. These are then sent to America to be genetically modified, and millions of the modified cells are grown before being transported back to the UK and returned to the patient’s blood stream. The modified cells then attach to the cancer cells and kill them.

The process of harvesting the T-cells from the blood is called apherisis and is similar to platelet donation or dialysis with blood pumped out through a vein in one arm then passed through a centrifuge before being returned (minus the T-cells) in the other arm. 

On the day of the harvesting Richard was hooked up to a very intimidating machine for some hours, and he looked very small and frail in the big bed with the machine whirring away, but we left happy. The machine had harvested sufficient cells for the process to begin – we were over the second hurdle!

It takes a long time to genetically modify cells and those weeks of waiting were the longest of my life. Richard was having ‘maintenance’ chemo, the mass in his side was getting painful and he was losing more weight.  We were effectively ‘shielding’ to keep him free from infections before the word had been invented.

Eventually we received the news that his T-cells were back in the UK. Richard had to go into an isolation room a week or so before the procedure - the ‘mother’ of all chemo treatments that would pretty much kill off everything (including his entire immune system). Richard had the ‘killer’ dose and was all set to go.

CAR-T Therapy

On 23rd September (day zero), his modified CAR-T cells were returned to him. Although the procedure was not complicated, there were a number of extra medical professionals in the room to see this new ground-breaking treatment. There was a real sense of anticipation, even reverence, in the room and I am sure it wasn’t only Richard and I that felt this. 

The cells arrive in a little dalek device that keeps them frozen at an extremely low temperature. The labels on the dalek were checked, and double checked, referenced to Richard’s medical labels and to his medical records. The dalek was opened, and with the dry ice smoke adding to the atmosphere in the room, the cells were defrosted and returned to Richard. The final hurdle!

Dangerous Side Effects

But not quite! The treatment is intensive, there are many extremely serious side effects. Richard was monitored hourly to begin with for psychological and physical side effects. This meant as well as hourly blood and temperature checks, he was asked questions about where and who he was, to identify simple objects and to check the consistency of his handwriting. I was now on red alert to watch for any changes in his behaviour.

After spending weeks without leaving the safety of his isolation room and having only myself and his son to visit him, the big day came and Richard was released. It was a massive day for us all!

Not Quite Home

But we were not allowed home just yet. Patients are required to stay within 30 minutes of the hospital until 30 days post CAR-T treatment because of the risk of specific complications in relation to CAR-T including cytokine release syndrome and immune effector cell associated neurotoxicity syndrome.

So we stayed with my dad for a month, either checking-in daily at BHOC in person or by telephone. I was also taking his temperature, checking his handwriting and asking him the usual questions about who and where he was.

Richard was a shadow of his old self. He had lost his hair again and weighed only 50 kilos. But as time passed, little by little, my husband came back to me.

Eventually, we were shown a comparison of the ‘before’ and ‘after’ PET scan of Richard’s abdomen. Even as I write this I can still recall the horror of seeing the ‘before’ scan – his entire abdomen was alight with the areas where the lymphoma was lurking - he was riddled with it, and yet his major organs had largely been unaffected. The ‘after’ scan was, by complete contrast and by some scientific miracle, completely clear.

A Happy Ending?

Richard’s six-month and twelve-month PET scans were clear. His weight is back to normal, as is his hair, and he has no lymphoma symptoms. The BHOC has continued to provide him with amazing care and support - despite the current restrictions as a consequence of the COVID-19 pandemic.

We are understandably nervous about the lymphoma returning – who wouldn’t be? There have been so few CAR-T lymphoma patients that nobody can tell us whether Richard is cured or in remission – and whether that remission will last. But the amazing science behind CAR-T, our incredible NHS and all the kind and professional people involved in his treatment means that Richard is alive today when the odds were so heavily stacked against him. All I can say is thank-you!  And I hope, with all my heart, that more and more cancer patients will be able to benefit from this life-saving CAR-T treatment.

Tracy