Ryan has felt quite well the past week and has been a bit more active, like walking from the room to the car, from the car park to the hospital, nothing spectacular but an improvement none the less.  He had 2 sessions of ECP (extra corporal photophyreresis) which makes him feel tired for the rest of the day but other than that seems to have been feeling ok, in fact better than he has in a long while.  The ECP treatment had been 2 sessions every fortnight but will now be 2 sessions every 4 weeks.  We are slowly reducing the immune suppressant and Ryan's t-cells are increasing without any adverse effects, at present anyway.  His blood counts are also increasing and his white blood cell count and neutrophils are now stable in the normal range for the first time in what feels like years.

This is obviously great news but although I am happy about this, I don't feel happy.  I have an overwhelming feeling of sadness because of circumstances that two families close to our hearts find themselves in.  I have thought so much about what I want to say here in this blog as saying nothing feels wrong, it has kept me awake at night, but it is simply too painful to truly convey how upset we feel about what is happening to both families.

Ryan has been very close to his friend Adam since meeting him in Greifswald in 2011, the boys had a connection right away and this has remained despite the fact that they don't get to see each other very often.  Adam has had to return home from the US due to complications with treatment.  His disease has not responded.  There is no more treatment out there.  In himself Adam is doing ok, he still has his defiant streak, his quick witted put downs to his Dad and Gareth if they monopolise FaceTime.  He and his family are constantly in our thoughts. 

During our time in Tübingen we have become friends with another family who are now in similar circumstances. This weekend we went to Munich to meet up with Tobias and his family and another family that we have met here.  Tobias relapsed a couple weeks ago, his treatment also failed after what looked like really promising news a couple weeks earlier.  Tobias is 12 and understands his situation, again there are no more treatment options.  I can't really put into words the courage that he has shown dealing with this news, he has a list of things he wants to do and has had a busy few weeks.  This Saturday he watched a football match in Munich stadium, something he has wanted to for a long time. 

Please keep Adam and Tobias, and their families, in your thoughts and prayers.

It's been an eventful week again; I wrote the last update while Ryan was having ECP, he was having a lesson with this teacher and feeling fine. Within minutes of posting the update things changed suddenly.  Ryan eyes were wide and he started to wretch, he went as white as a ghost and he lips went blue.  We called for the nurse and she took his blood pressure which was dangerously low.  She called for help and 2 doctors and more nurses came rushing in.  His bed was tilted backwards so his head was lower than his heart and we managed to keep Ryan awake by talking to him while the doctors interrupted the ECP machine and made it start to return his blood quicker than it had planned to.  Apparently 'this sometimes happens' as too much of Ryan's blood was in the machine and not in his body causing his blood pressure to plummet.  As soon as the blood was returned he started to regain colour and his blood pressure started to improve.  Panic over.  

He was tired for the rest of the day and then during the evening and night his temperature started to rise and he woke several times with diarrhoea.  We spoke to the doctor in the Day Clinic the next day and he said that provided that Ryan was ok in himself we should just monitor the situation and 'see what happens'.  As the levels of steroid had been reduced earlier in the week it was not a complete surprise that Ryan would get a temperature and the upset tummy could be a flare up of GvHD.  It was the first time we had 3 hospital free days since January and so none of us were keen to go into hospital unless it was absolutely necessary, and as he was well in himself we just stayed at the parents house.  However on the Tuesday morning it was clear that Ryan was not right, he woke with a headache and felt sick and was quite sleepy.  When we got to clinic as planned for an infusion of anti-fungal medicine he fell asleep.  His blood pressure was fine, his blood results showed he had a raised infection marker but nothing more than that. We talked through the last few days with the doctor and he suggested that Ryan needed a higher level of hydrocortisone due to possible poor absorption due to the diarrhoea.  We gave him a higher dose and within an hour he was his usual self!  The temperature and diarrhoea have both settled again and tests on the stool have shown no pathological cause.

The next day, Wednesday, they suggested we had a check up to see what the infection marker was doing and it had halved.  However they then had the results of the previous Thursday's t-cell analysis which showed over 30% of t-cells originated from Ryan and so they urgently got the results of the test done the previous day which showed 12%.  It is therefore possible that the fever and diarrhoea over the weekend were a result of the two immune systems 'battling'.  No one will know for sure, but either way the increase in autologus t-cells is not a good thing.  However as Ryan was again feeling well the consultant was able to reduce the immune suppressant, Cellcept, by 25% to try and allow Ryan's new donor derived t-cells to become more active and overpower his original ones.  We have to wait until Monday before another analysis of the t-cells is done and hope to get the results soon after.

All in all the past week started badly but has ended with Ryan feeling ok again.  We have no hospital this weekend and hope that he will continue to feel ok although he still has very little energy so we won't be doing very much.  What we really need is to see the back of the autologus once and for all, but at the same time we don't want a flare up of GvHD - such a fine balance to get things right and such a long time to get there but it will be worth it.

When I start to write these updates I always try to keep them short, but that never seems to happen lately. Ryan has had so many different issues going on, all of them equally significant.  But gradually Ryan's condition is improving.

Since the last update his liver enzymes continue to slowly reduce, indicating that the inflammation due to toxicity is reducing, his blood pressure medication was stopped and his blood pressure has remained within the normal range, his electrolytes have been stable without the continuous pump, the oral medication to supplement electrolytes is slowly being reduced, his hydrocortisone is now back to the normal level and the autologous t-cells (originating from Ryan's original immune system) have reduced from 13% to 6%, and as at Monday's blood test there are no viruses in his leukocytes or blood plasma - all of these things are huge steps in the right direction.  

Loosing the pump has given Ryan a real boost, he has the freedom to move around although not the energy to do so.  He has lost a total of 2.5 kg, he never had much fat to start with and so most of the loss is muscle.  He is painfully thin and due to the GvHD of the stomach we have had to give him low fat food.  Now though his stool has returned to normal and so we can start to introduce foods to help him gain weight, it is a case of try it and see what his stomach thinks of it.  

We have come to realise that the recovery from GvHD is going to be a slow process.  We don't see improvement in Ryan daily but as each week goes by he is better overall than the last.

His mouth and skin still show signs of GvHD although both are much improved. He still has the HHV-6 virus in his mouth which causes some inflammation and blisters but surprisingly these don't bother him too much. He still has a cough too, it now sounds very loose but there is nothing in his lungs, the doctors think it could be inflammation of the mucosa (lining of the throat) but the cause is not known.  As he has no fever or infection marker it is currently not being further investigated (as the original CT scan was clear and his lungs are listened to daily) 

In himself Ryan is a lot happier than a few weeks ago, the visit from his auntie and cousins had the desired effect and really cheered him up, and although he still desperately wants to go home he has stopped being tearful about it.  The weather has improved and the sun has come out and so it hopefully won't be too long before he feels up to doing some gentle activity outside.  

Life is a roller coaster......

A few days after my last update we had some unexpected bad news during a routine clinic visit: the Adenovirus and HHV-6 viruses had both reappeared in the leukocytes as at the blood taken 1st April (within the white blood cells). 

A few weeks ago we learned that the company that manufactures the only drug available to contain the virus has had to stop production due to microbiology problems and it was not available for the foreseeable future.  This is a worldwide problem and has very serious implications for patients with the virus in the blood.  After discussions with the consultant here Gareth and I were tested to see which of us had the most effective t-cells against the virus and yesterday Gareth had about 500ml collected to be prepared ready to be given to Ryan should the copies of the virus in the blood increase.

In addition we were shocked to learn that although there are now good numbers of T-Cells 13% of these were now Ryan's.  Apparently they had first appeared at the end of February and had been increasing 'a couple percent each week'.  I think the doctors in the day clinic had thought we had known this already and so had not mentioned it, they said it was very unusual to see reemergence of autologous t-cells with active GvHD and could not explain it other than to say Ryan's were 'incredibly strong'. 

At this level they are not a huge threat, but obviously have potential to be a massive problem.  Currently as the GvHD of the gut and liver has improved and the mouth and skin are improving slowly we can start to reduce the remaining immune suppressant and so on Monday we reduced hydrocortisone from 3 x 15mg to 3 x 10mg (Ryan's usual dose is 3 x 5mg). 

The only adverse reaction so far has been an increase in temperature and so hopefully next Monday we can reduce again.  Then the remaining immune suppressant, Cellcept, will start to be reduced.  The reduction has to be done slowly as doing this too quickly could allow the T-cells to become too aggressive again and trigger GvHD.  It is a balancing act, with huge consequences either way.  The outcome we are looking for is obviously for the immune suppressant to be gradually weaned off allowing the donor derived t-cells to destroy the  autologous t-cells and viruses but not causing Ryan problems.  

On Wednesday afternoon we finally got the results of the outstanding virology tests of the liver biopsy which confirmed that the inflammation of the liver was caused by toxicity of medication.  As there was no evidence of virus infection this meant that yesterday Ryan was not given the daily 2 hour IV infusion of anti-viral medicine.  This is very toxic and makes Ryan feel tired as well as suppressing his bone marrow and we were pleased that this could stop.

We also got the results of the re-staging scans and were thrilled to learn that both the full body MRI and MIBG scan showed no evidence of disease.  Ryan has bone marrow tests planned for the week after next for completeness. 

And today we got the results of this Monday's blood virology and were really pleased to learn that the ADV virus is again gone for the leukocytes, although the HHV-6 virus is still present.  The adenovirus is however still present in the stool.  

This week Ryan has had two 4 hour sessions of ECP (the UV light treatment for GvHD).  It usually makes him feel very tired but he has fought off the tiredness well as his auntie and cousins are here visiting. Despite spending so much time in hospital it has really lifted his spirits to see them all which is just what we were hoping.  

For the past few days the doctors have been reducing the levels of electrolytes in the portable pump.  It is the only way to see if the kidney has recovered as the levels will not become high, they will just become stable within the normal ranges.  Since the reduction most have remained stable within normal ranges although a few more tablets have been added until we are sure that they are not needed intravenously.  Today the pump was disconnected and the next few days will show whether his kidneys have stopped 'leaking'.  Ryan is so happy to be free and not connected, it is the first time since being admitted to hospital on the 1st February that he can move around freely without worrying about being connected and it is truly lovely to see him enjoy his freedom.

Improvement

Things have improved here since my last update. Most noticeably Ryan himself. The increase in hydrocortisone has greatly helped the GvHD of the skin and he has walked more this week than he has in the past month. There has also been an improvement in his appetite and he has started to feel hungry at times and is eating willingly again. His stool also seems to have begun to improve, hopefully this improvement will also continue. 

The liver biopsy didn't reveal any signs of infection or GvHD and is indicating toxicity of medications. We are still awaiting final results of virology tests, which will be a few more days, but it is hoped that the liver will gradually recover by itself. One of Ryan's medicines which is particularly toxic to the liver was stopped as soon as the enzymes started to rise, over the past few days these have started to fall and will hopefully continue to do so. 

The other change to medication is that Tacrolimus (the immune suppresent drug that is most effective against GvHD) was being gradually reduced and has now been stopped and replaced with a less aggressive immune suppresent (Cellcept).  This will hopefully mean that Ryan's blood pressure and kidney problems should start to improve - in fact just days after stopping the drug his blood pressure medication has been reduced from 4 times daily to twice daily which is a really positive sign.  Once his kidney's start to function properly he will no longer need the continuous infusion of electrolytes.  For Ryan this will be a huge benefit as the bag contains one litre of fluid when it is replaced each day and is simply too heavy for him to carry around in the special backpack provided with the pump.  Fingers crossed we will see this improvement soon.

The IV anti-virals will continue until the full virology is reported which means that Ryan has a 2 hour long infusion each day when we come to clinic for blood tests and a new bag of electrolytes. At best we spend 4 hours in clinic. Ryan is totally fed up of hospital, he hasn't had one hospital free day for over 2 months and it is taking its toll. He is not his usual happy go lucky self and is tearful about being connected which is most unlike him. Some days, when additional medicines are required, we can be in clinic for as long as five hours, combine that with a scan or ECP therapy and the whole day is gone. 

But next week Ryan's eldest cousins arrive for a visit with my sister Jackie and this is something that he is really looking forward to.  Fingers and toes crossed that the improvements we have seen this week continue and he enjoys his time with his cousins, despite the fact that most of the days will be spent in hospital.

A lot has happened in the ten days since my last update.  Some significant good news in that the adenovirus that was in the blood has gone (as at the test taken 18th March) although it remains in the stool.  However the HHV-6 virus remains in the leukocytes.

Ryan developed a cough a couple weeks ago, a dry non-productive one, but as it continued a CT scan was done as this could be a sign of GvHD of the lungs.  Nothing showed on the scan but the cough is no better and a further CT will be done if it doesn't resolve.  His skin has also continued to get worse, especially the palms of his hands and soles of his feet which are bright red and inflamed, so much so that it is often too painful for him to walk.  This is being treated with steroid and immune-suppressant cream but isn't improving. His arms and legs are also covered in a red bumpy rash and really looks quite awful.

Unfortunately Ryan has continued to have blood pressure problems, needing an echocardiogram to check there was no fluid around his heart. His liver enzymes have become elevated again and not stabilised resulting in an ultrasound to check for veno occlusive disease and then, as the enzymes continued to rise, an emergency liver biopsy yesterday.  Ryan needed to stay in the ward overnight as there is a significant risk of secondary bleeding, luckily there are no signs of this having happened.

The results of the liver biopsy yesterday won't be known until next week due to the Easter break.  The consultants believe the cause of the problems to be either a virus attacking the liver or a return of GvHD although have said it could be toxicity of medication or even a relapse of neuroblastoma.... To try and stop further inflammation of the liver Ryan has been started on IV anti-virals again and his hydro-cortisone dose has been increased.

On top of all this we are at the time for the dreaded re-staging which means full body MRI and MIBG scans.  The hour long MRI took place earlier this week and the MIBG scan is scheduled for next Wednesday/Thursday.  Bone marrow tests may also be needed.

All in all it has been a rubbish couple of weeks for Ryan and a stressful time for Gareth and I.  My parents arrived for a visit this week and we had hoped to spend time with them at the apartment they rented but that hasn't happened as the majority of time has been spent in hospital.  But Ryan has enjoyed seeing his Nanny and Grandad and hopefully once he is discharged today he will be able to see a little more of them tomorrow and before they leave on Sunday, although he still has to spend a few hours each day in clinic.

Ryan has managed to sleep at the parents house since being discharged to the day clinic last Wednesday.  It has meant a trip into clinic each day, the first morning after being discharged we had to be in at 9 and were still there at 1, other days have been shorter visits although nearly always an hour or two.  

Ryan blood counts seem to have stabilised again, and the need for GCSF (to stimulate the white blood cells) is reducing.  His platelets and HB, both of which are effected by ECP, have also stabilised but its possible that he will need transfusions of both next week when he has ECP again.

We had good news on Friday, based on the previous monday's blood test, that the level's of adenovirus in the blood plasma had reduced to 'less than 1,000' and the HHV-6 virus is now only in the leukocytes and not in the blood plasma.  Both of this is great news and shows that Ryan's bone marrow is slowly recovering and fighting against the viruses, together with the anti-viral medications.

Ryan is managing to eat sufficient to maintain his weight, his appetite still isn't really there yet but he understands that he has to eat if he wants to stay out of hospital.  His tummy is still effected by GvHD and so we have to be careful what foods he eats but he has found some things that both he and his tummy like.  

As the levels of the immunosuppressent in his blood reduce the GvHD of the skin has become more noticeable again.  His skin looks 'irritated' more than anything.  Sometimes a rash is clearly visible, then other times it is gone again.  His blood pressure caused problems again this weekend, causing him to wake up with a headache and nausea and as soon as we got to clinic he was sick and then fell asleep.  Apart from this he has mostly felt ok since leaving hospital, he is still exhausted and very ready for bed at 7.30pm,  in fact if it wasn't for the schedule of medicine that runs from 7am until 7.30pm he would be asleep much earlier i'm sure.

Here is a photo of the tablets he is taking each day - in addition to this there are 8 syringes of medicine and a steroid mouthwash…..

We had expected an overnight stay in hospital yesterday (for the drug meant to contain the adenovirus) but when we arrived at the ward at 9am laden with suitcase containing the x-box and clothes and bags of food and medicines we were told that an emergency admission during the night meant that Ryan's room had to be allocated (although not sure why no one rung us) and so we are now expecting to be admitted tomorrow……