Ryan's story

Ryan was diagnosed with Stage 4 High Risk Neuroblastoma N-MYC amplified in July 2008. He was out of treatment for just over a year when in November 2010 our lives were again turned upside down when we discovered the disease had returned in his bones and bone marrow. After a year of treatment re-staging scans in November 2011 showed that he had again achieved remission.

However just 3 months later, in February 2012, end of treatment scans gave us the devastating news that the disease has returned, this time with a tumour near his spine. In March Ryan started 4 weeks of radiotherapy followed by chemotherapy which is on-going. Re-staging scans in May and August showed no evidence of disease. On the 4th September 2012 Ryan received treatment in Tubingen for a haplo-identical stem cell transplant. He is a happy, active boy who is now enjoying life to the full.

Thursday, 28 February 2013


We didn't get to leave hospital after all.  The blood pressure became quite a problem causing severe headaches and nausea.  Ryan stopping eating again and generally felt quite rubbish.  The cause is suspected to be the higher levels of the immunosuppresent drug Tacrolimus.  The switch from IV drugs to oral has meant the drugs are effecting Ryan differently and it is a fine balance getting the levels right.

The immunosuppresent drug has now been reduced and the nausea has gone but the blood pressure may take a little longer to correct itself.  Ryan has been started on blood pressure tablets and today has been his best day since the problems started last weekend.

And so instead of being discharged to the parents house Ryan has been moved out of isolation in the bone marrow transplant unit and into a room in the oncology ward.  (There is no longer swine flu on the ward, thankfully)  We have our own room and as Ryan has an infectious virus in his stool we are 'barriered'. This means that we are not allowed to use the communal kitchen, as children with low immune system eat in the kitchen on this ward, and so if Ryan or us want any food or drink we have to buzz for a nurse to get it for us. (As if they haven't got enough to do!) This is not ideal as you can imagine, although the staff assure us that is has to be this way.

Looks like tea and toast will be on the menu for Gareth and I of an evening, although Gareth is considering buying steak and potatoes to see if the nurses would cook steak and chips for him!  

Monday, 25 February 2013

I talked a lot about treatments but I haven't really gone into much detail about how Ryan has been feeling in the last couple updates so thought I would take the time to try and put it in writing.  

I had said that Ryan is still very tired, although weak and exhausted would probably have been a better description.  He is thin and has lost muscle as he has been in bed so long.  

The need for him to be an in-patient has changed now that his stomach is repairing and can tolerate the medicines orally.  Most of his medications have now been switched to oral to enable him to be discharged to the parents house later this week.  He is on so many medicines, several of which have unpleasant side effects.  The most recent side effect to materialise being high blood pressure causing headaches which have also made him feel sick.

His treatment will continue though and it will mean that every day he has to come into hospital for either ECP or IV anti-virals, anti-body and/or anti-biotics.  Although it is a positive step it will actually be harder on Ryan initially.  He will need to drink a minimum of 500ml per day and will need to eat as his IV nutrition will stop when he is discharged.  His taste buds are not back yet, his tongue is still coated with a layer of dead white cells although it is improving. 

At present he is eating the equivalent of about one meal a day and drinking about 250ml.  Apart from obvious reasons he also needs to eat to ensure there is something in his stomach other than medicine, as the medicine alone will make him feel sick.  Already it feels that we are constantly asking him to swallow medicine, eat or drink.  He also needs creams applied 4 times a day, something that he hates.  

He is feeling quite low, tearful at times, and misses his home and friends very much.  He still manages to play on-line with friends for a bit each day but often has to quit because he is tired or has a headache.  The ECP causes his eyes to be sensitive to UV light, including the TV, and so he has to wear special UV glasses.  He is currently wearing some which are too big but has now chosen his own orange (!) ones which should be arriving in the next few days.

Unfortunately there is still a long way to go before there is any talk of Ryan returning home to the UK, something that he is very keen to do.  For the time being this is the best place for him.  

Sunday, 24 February 2013

Over the past week Ryan's stomach has slowly continued to improve, so much so that he did not open his bowels for over 24 hours and when he did it was not completely liquid.  As of today he can return to eating the 'clean diet' that he has been following since his transplant in September.  Although this is still restrictive it is a lot better than he has been allowed in the past few weeks and he is very pleased about this.  

His liver enzymes are still elevated but only 1 or 2 of them and not all, there is only minor evidence of GvHD on his skin and his mouth is slowly but surely improving although he can not taste everything yet.

Unfortunately the viruses are still present as they were last week; ADV in the stool and HHV-6 in his blood plasma.  He has been started on additional anti-virals to try and contain them.  The doctors are also keen to reduce the immune suppressing steroids as quickly as they can to enable his t-cells to multiply and attack the viruses and so in the past 7 days they have reduced the dose from 12mg twice daily to just 5mg twice daily.

Each time they are reduced Ryan gets a temperature, although it cannot be assumed that the reduction in steroids is the cause, each time it has to be treated as a potential infection.  It happened again this week and the doctors said the cause could have been one of 4 things: the reduction in steroids, the engraftment of the new stem cells, the virus or a bacterial infection.  Either way in the past 24 hours the fever is subsiding and the steroids have not needed to be increased again.  

It has been 11 days since the stem cells were infused but there is still no sign of his blood counts improving; today he is having a blood and platelet transfusion.  They usually appear 10-14 days after infusion and so we are hopeful to see signs of engraftment in the next few days.

Ryan is mostly feeling very tired, quite understandably. There is so much going on in his body.  But the doctors are very pleased with his progress and are still talking about possibly discharging him mid-week if he continues as he is.

Monday, 18 February 2013


As seems usual that I have good and bad news but overall we are still feeling positive about how things are going here in Tübingen.

Ryan has continued to improve each day and now is only experiencing watery diarrhoea once or twice a day, at its peak it had been over 3.5 litres and is now under a litre.  His skin and liver enzymes both got worse towards the end of last week but are now starting to improve again.  This may be in direct response to the reduction of the steroids, but they have been reduced again today and so we will see what happens.  In Ryan himself though we have seen the biggest improvement, he has been able to stay awake more, is his usual happy, chatty self and is hungry and wanting food.  In fact the wanting food part is a bit of a problem, as his stomach is still repairing and not really ready for food.  He is allowed to eat plain, bland food, which is low in sugar and fat, no vegetables or fruit.  Ryan is struggling to understand why eating is all of a sudden not something that is being encouraged.  We have explained time and time again why and that this is just a short term thing, while his stomach heals, but with a hunger driven by steroids, Ryan feels like he is going to 'starve to death, like his character on Minecraft!' In fact he is drinking a special drink, an 'elemental' feed which is already broken down so that it can be easily absorbed by his stomach and gives him everything that he needs but this isn't the same as actually eating.  Overall though the doctors are extremely happy with him and are talking about switching some of the IV medicines to oral, and if his progress continues, will talk about discharging him to out-patient treatment sometime next week.

But the bad news; the virus (Adenovirus)  has shown up in his stool again, and now there is also another virus (HHV-6) in his blood. Both can be very serious to a post transplant patient but at present neither seem to be causing symptoms or problems and so we continue to hope and pray that this is continues.  Once the steroids are reduced further and his immune system is less suppressed the hope is that his t-cells will deal with these viruses.  

We are taking things a day at a time, as we know only to well how quickly things can change, but for today we are feeling positive.

Thursday, 14 February 2013

On Tuesday they collected a total of 8 million of my stem cells.

They have been processed to separate as many t-cells as possible from the stem cells but anticipate that a few thousand will remain. They say that these additional t-cells will not accelerate the GvHD in their experience.

Yesterday Ryan received 4 million of these cells via his hickman line. The remaining 4 million have been cryopreserved. The purpose of the stem cell infusion is to give Ryan's bone marrow strength. His bone marrow, which has originated from my donated stem cells since the transplant in September, has been attacked by his surviving T-cells for several months leaving his counts very weak. These new stem cells will find their way to his bone marrow, engraft and develop into either platelets, HB, white blood cells etc.

This should then reduce his dependency on blood products and GCSF. However occasionally active GvHD can continue to cause thromopenia (low platelets) but if this is the case the additional cyropreserved stem cells can be used once the GvHD is controlled.

The frequency of Ryan's stool continues to be much improved - approx 4-5 times in 24 hours but the volume is still quite high. Each one being approx 400-500 of black looking water. He is very tired and weak but managing to play the x-box each day and speak to some friends

He is asking for food but his stomach cant really tolerate food yet. It is so hard telling him he cant eat when we have spent years encouraging to eat well. We are going to chat to a dietician and see what foods they suggest at this stage. I dont think spaghetti bolognese wi be one of the options though....

Ryan steroids have been reduced from 40mg daily to 30mg as these cause the most immune suppression but already his skin and liver enzymes are slightly worse and if this continues they may need to be increased again.

And lastly some very good news: the stool sample from monday is negative for adenovirus which means the virus is below the level of detection . They suspect that Ryan's t-cells have dealt with this virus as the anti-viral drug was to try and prevent the virus spreading.

Tuesday, 12 February 2013

ECP

The change in Ryan in the past 48 hours has surprised not only us but the Dr's too. His stool volume has reduced from 3.5 to 2.5 litres but the biggest improvement has been in the frequency of stool - this has changed from 30 minutes intervals to 4-6 hours! His mouth continues to improve daily. This week he will receive 2 further sessions of ECP and i thought i would explain what that involves:

ECP: Ryan is connected to a machine by his double lumen hickman line, blood flows out at a rate of between 15-20ml hour flows into the machine and is spun to separate white blood cells from red blood cells. The process takes between 2-3 hours depending on how the hickman is working. The red blood is returned to Ryan and the white blood cells are collected and then treated with light which is said to influence the behaviour of the t-cells. Once treated the WBC are also returned to Ryan. The treatment usually has an effect after 2 weeks, which is 4 sessions.

As usual it doesnt seem possible for us to have good news without bad. We learned yesterday that low levels of adenovirus have been found in Ryan's stool sample of last week. This is a very dangerous virus to a post transplant patient and so needs to be treated aggressively to try and prevent it spreading into the blood. Ryan blood and stool are tested twice a week to monitor the virus levels. We have been told it can stay 'dormant' in the stool and so we can only hope and pray that is the case for Ryan.

Today I had my stem cells harvested, the procedure went well with the exception of a temperamental needle what constantly needed repositioning. My white blood cell count was 62.2! (normally 1.5-5) at the start of the collection so it is expected to be a good harvest.


Sunday, 10 February 2013

Treatment

Since the diagnosis was confirmed on Wednesday afternoon much has happened; Ryan as had the anti-body infliximab, 2 sessions of extra corporal photopheresis (ECP) and also an infusion of mesenchymal stem cells (MSC). They didn’t need a donation of these cells from Gareth or I as they had a suitable match frozen in storage. It is amazing how quickly the hospital here have been able to arrange these specialist treatments and we are very grateful for this. The only down side being that we did not have opportunity to ask much about what the treatments involves in advance of having them, which meant that often we had to tell Ryan what was happening last minute and didn’t have much time to prepare him.

I know that everyone is hoping that I will say that Ryan is a little better but in all honesty this isn’t going to improve daily, more weekly.

His mouth is showing signs of improvement in that the thick white coating of his tongue is very slightly pink in places. He has started drinking water again which is a good sign. We cant see the rest of his mouth as it hurts to open it. His skin is much the same although a new area on his head and neck can be seen. His liver enzymes are almost all within normal ranges but the diarrhoea is impacting on the liver function now too.

The GVHD of the gut causing sickness and diarrhoea remains the worst problem; the sickness is much better controlled after tweeking some of the anti-sickness medications. The diarrhoea on the other hand is relentless. We were told he was passing between 2-3 litres a day, more fluid that they can give him. The stool is watery and often red with blood. It floods out of his little body. I have to fight back the tears when I change him and clean him up; it is devastating and totally exhausting for Ryan. He weighs 2.5 kilo’s less than he did and is painfully thin. He has started to experience pain but it is intermittent and he is managing with paracetamol. The doctors are surprised that he isn’t on morphine but this is a good thing as morphine, although great for pain, brings a whole host of new side effects.

The doctors had told us that his stomach was likely to get worse before it got better – there is no quick fix for GVHD. We just have to hope that there is not a progressive deterioration.

Sleeping is obviously a problem for Ryan, until a few days ago he sat on the commode every time he needed a poo, sometimes he was only just settled when he needed to go again, rarely did he get chance to sleep more than 15 minutes at a time. He did not have one accident but it was very stressful for him. He was obviously very sleep deprived, he was almost hallucinating and waking from broken sleep with racing heart and feeling panicked. The doctors spoke to us about sedating him during the night to give him chance to sleep, this is often required for these circumstances, but this upset Ryan very much. So we talked to him about how essential sleep is and that if he didn’t sleep he would be even more poorly. We suggested he use a nappy at night and we would change it immediately – he reluctantly agreed and although it meant he wasn’t in and out of bed the sleep situation was no better. So then we asked him to try not to wake up when he needed a poo, to trust us to check his nappy and change it only when needed and to try and stay relaxed while we changed him (so hard for a proud 6 year old to have to do this but Ryan knows the alternative and is trying really hard). The nappies cannot always contain the volumes of stool, it floods out the nappy and so his bed is covered in changing pads so we don't have to keep changing the sheets. This seems to working for him and although his sleep is still broken he is getting about 8-9 hours a night which has had the desired effect and meant that he can be awake more during the day.

He is talking more and interested in watching his favourite YouTube video’s again on his beloved ipad. He has even requested that we bring in his x-box and has played on-line with a couple of his friends. Obviously he is easily tired, which he finds frustrating, but at least he is doing something that he loves which makes him feel slightly normal.

Gareth and I are taking it in turns sleeping in hospital with Ryan and sleeping at the parent's house. In hospital we get a total of an hours sleep on a bad night (if you add up the ten minutes here and there) and a total of 3-4 hours on a good night. The feeling of panic I felt has gone and we are both coping ok. Gareth has always said he will sleep when he's dead and so he even struggles to sleep at the parents house, and on my nights at the house I try not to think, but the sounds of machines alarming fill my head even though they arent there and I have to let the tears that I hold back all day fall silently onto my pillow.

Ryan has a superb medical team looking after, he is also visited regularly by the doctors from the day clinic and gets regular pop in's from the director of the children's hospital. Everything is being done to support him through this period and get him back to good health.

Wednesday, 6 February 2013

Graft Versus Host Disease

The stomach biopsy taken yesterday confirmed no presence of viral or bacterial infection and today a diagnosis of GVHD has been confirmed. This is effecting his skin, mouth, liver and gut.

Skin: overall his skin is improving, the only remaining signs are on his feet, hands and groin. The itching is all but gone - so one piece of positive news.

Mouth: Ryan mouth started to detiorate last Tuesday and has progressively got worse, the roof of his mouth is raw and his tongue is completely white so are his gums in places - Ryan says his mouth is very very dry and you can see his gums stick to his teeth when he talks. Now a diagnosis is confirmed and viral and bacterial infections have been ruled out Ryan has been started on a steroid mouthwash which should gradually allow his mouth to repair.

Liver: the liver enzymes are slowly reducing and, although they are still high, the doctors say they are happy with this improvement which they attribute to steroids.

Gut: the biggest problem for Ryan, causing watery diarrhoea often 2-4 times an hour, the longest interval being about an hour, but only occasionally.  There is occasionally blood and lately mucus and gut lining being passed too which is very upsetting to see.  He has also had persistent nausea and vomiting although this has improved in the last 24 hours as we are tweaking the numerous anti-sickness medicines. He has lost approx 2 kilos in weight. He is totally exhausted.

Today he has been started on an antibody called inflixamab, which will target the gut GVHD. The steroids and immune suppressant medication that has helped the liver may also start to impact on the gut as the therapeutic doses are reached.  Tomorrow he will also start a treatment called ECP which I believe is a form of light therapy which has shown good results in treating both liver and gut GVHD. they are also considering Mesenchymal Stem Cell therapy (MSC) which is way above may head and I can't begin to explain how that works but again they have seen good results with this treatment. This involves stem cells being extracted directly from the bone marrow and used as a targeted therapy. They will select either Gareth or myself as the donor for this procedure. Gareth has volunteered but we will go with however is the best candidate.

The purpose of these three therapies is to, hopefully, speed up the recovery process (which even then is likely to be months rather than weeks) and reduce the amount of time that steroids are used.  The biggest problem with using steroids is that they suppress the whole immune system and so increase the risk of infection.

Infection is the biggest threat to Ryan.  We have been told that now is the time to be paranoid about being around other people who might have coughs, colds etc. Then today we learn that swine flu is confirmed on one of the wards, effecting oncology children and the nursing team! But already the whole hospital is now being told that face masks are mandatory, we should not eat in the communal ward kitchen but bring the food back to the outer part of Ryan's room and eat there.  We are really happy to follow these rules and hope that all other visitors to the hospital do too.

Vanessa Riddle, who also had a transplant a few weeks before Ryan, had arrived to start her 4th cycle of antibody therapy but when the family have very wisely decided to delay treatment until the swine flu is gone from the ward - hopefully when Vanessa returns Ryan will be feeling a little better.

Tuesday, 5 February 2013

Ryan's night was much the same, no significant deterioration and no improvement either.  He felt sick and was sick and overall had less sleep than ever and so today he was back to being very subdued and not speaking.  The procedure for the investigation of the gut took place in his room and he was so good while the consultant set up all the equipment and the only questions he wanted to ask were what was the consultant's name and how long would it take.  Dr Sturm introduced himself and said it would take 15 minutes.  There were no complications and Ryan woke up from the sedation without any tears and soon was back to sleep again.

This afternoon the doctor on the ward has confirmed there are no evidence of bacterial or viral infection and that by tomorrow the analysis would be complete and a diagnosis of GVHD is expected.  This gives him the ability to add some medication to try and reduce the frequency of the bowel movements and to try and retain fluid in the blood which will be passed as urine and not passed through the bowel.

Ryan has so many side effects of both the GVHD condition and the numerous medications that he is on that I cannot write about them all, it is not expected that his condition will improve short term, this will be a gradual process.

Monday, 4 February 2013

Ryan's situation is no better; his diarrhoea and sickness are both slightly worse.  His mouth is worse and looks the way it did when he had severe mucusitus, but this is most likely also GVHD, we are awaiting some final swabs results. The liver enzymes are still mixed although there are signs that the liver is very slightly improved.  His skin is better and there has been no itching for a couple nights which is one small bonus.

He is sleeping no more than an hour at a time day or night due to the constant sickness and diarrhoea. Last night he was started on a form of IV nutrition which gives his glucose, protein and carbohydrate but no fats as his liver is already under stress.  This will not give him 100% of his dietary requirements but will give him something. 

Today he has managed to stay awake longer than the past 3 days and this may be due to the nutrition. He has also spoken a little more today too - the past few days all he had really managed to say was 'sick bowl' and 'I need a poo' If you ask him how he is feeling or anything else he hasn't been answering but today there is a marginal improvement.  

Tomorrow they have arranged a biopsy of the gut as they say it is essential to be 100% sure of what they are dealing with GVHD and not another form of infection. This will be done under GA. They also still plan to take a biopsy of the liver later this week.  Once a diagnosis is secured they have several treatment options that they intend to put into action, we don't have full details of these yet but they all sound cutting edge treatments and are intended to speed up the recovery process.  That said we know how difficult GVHD is to treat and are unsure of any time scales. 

I will try and post brief updates frequently as I know that many friends and family are worried and prefer to know what is happening, we know Ryan is loved by many people and that he is in many thoughts and prayers.  

Sunday, 3 February 2013

Ryan's condition has slowly worsened since Wednesday. He was started on high dose steroids and these have reduced his fever to normal although the liver enzymes have showed a mixed response with some reducing and some increasing further. Since Wednesday Ryan gradually developed diarrhoea and has been feeling nausea most days, today he has started being sick too.

The tests have slowly come back negative to infection and so the Dr's think it is most probable that his symptoms are caused by GVHD, which could now be effecting the gut and mouth in addition to the liver. His mouth lining has turned white and started to break down in places (although he says it isn't painful just dry). The liver biopsy has been requested and should be done early next week to give a conclusive diagnosis.

He hasn't eaten since Tuesday, has been exhausted and sleeping on and off through the day. As he had been drinking well and was ok clinically (based on blood results) they said he could be treated as a day patient and not admitted. We have been going into hospital each day for iv medication.

However by yesterday we became increasingly concerned, as his diarrhoea worsened and he slept almost all day and so he was admitted to hospital at our request.

He has not been this poorly in a long while, even through this most recent transplant. It has also come as such a shock as only days before he had been ski-ing and having such well deserved fun. We are totally devastated but remaining positive that the Dr's will do all they can to improve Ryan's condition as soon as possible.

My stem cell harvest has been delayed by one week due to lab time for processing of the cells.