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.

Treatment

Ryan's story prior to March 2012 can be found on the page named Ryan's story.  This page was created to try and keep people informed of the details of Ryan's treatment from his 2nd relapse onwards.  However things got a little complicated for Ryan after October 2012 and it was not possible to keep this page up to date.  Initially his body started to reject the haplo-identical transplant and then he developed stage 4 Graft Versus Host disease.  He was very poorly and remained under the expert care of the hospital team in T├╝bingen, Germany until July 2013 when he was finally well enough to return home.

He is now 8, is in his 3rd complete remission and enjoying being a 'normal' boy, and doing all the things that normal boys do.  We are happy to share Ryan's treatment experiences with anyone that would like to know the detail, if it can help with decisions you are facing.  You can contact us via our facebook page using the link on the right of this page.

Treatment update 6th October 2012

Ryan continued to react to ATG with high fevers and low pulse but once that phase of conditioning was complete we were surprised at how well he tolerated the chemotherapy phase of the treatment.  It was not until Ryan received Melphalan that we was actually sick, the supportive care during treatment is excellent and so anti-sickness are given routinely, however if the children are sick additional drugs can be added to try and stop the sickness and in Ryan's case we opted for a continuous infusion and it worked really well and the sickness did not reoccur.

My stem cells were collected on Day -1 and I was fortunate in that enough stem cells were collected in the first 6 hours and so I did not need to have the procedure repeated the following day.  In fact 23,000 stem cells were collected and 10,000 is the figure they are hoping to collect over the two days.  The stem cells are processed in a lab and given to Ryan fresh the next day, Day 0.  We were told that between 30-50% of the stem cells are lost during processing but in Ryan's case he received 18,000 stem cells which is a huge amount.

At this point in the treatment Ryan was still eating and drinking well, he had no signs of mucusitus and looked great.  He had been active and happy throughtout the conditioning treatment.  This is such a huge contrast to the condition he was in at this point in treatment for his auto-logos transplant in 2008.

By Day +3 Ryan showed signs of developing a sore mouth and throat but said he didn't need any pain relief.  TPN (IV nutrition) is started on day +1 and so there was no longer any pressure in him to eat
although he continued eating small amounts until Day +5.  During the next week he was less active and felt tired but still happy to see the play lady, teacher and physiotherapist that all came to see him day sine he was admitted.  

The care that he received in the KMT ward was excellent, in every aspect. The nurses were experienced and knowledgeable about treatment and had more authority that the nurses are permitted in England for example they are able to increase morphine the minute the patient experiences pain without having to wait for the authority of a doctor.  The doctors were friendly, extremely knowledgable and reassuring and we all had a great relationship with everybody on the ward.  If you 
are reading this information because you are considering this treatment please don't hesitate to get in touch if you would like more detailed information of Ryan's experience, we know that all children are different but knowing someone else that has had a positive experience is always a good thing. We can be reached at ryansappealpage@hotmail.co.uk

On Day +8 Ryan spiked a temperature which persisted, routine anti-biotics were given but no evidence of infection was found and his CRP was unremarkable. After thorough investigation the doctors confirmed that Ryan was experiencing prolonged engraftment syndrome, which meant that his body was reacting to the new stem cells and so they started him on a steroid to suppress his body's reaction.  At the same time we were told that in all other respect Ryan was doing extremely well and 
would be moved into the oncology ward while his temperature stabilised and he withdrew from morphine.  We were assured that we would have our own room but at the last minute that did not materialise and so after much negoiation we pushed for Ryan to spend the nights at the parents house and the days in a shared room wearing his mask.  With continued pushing by us his withdrawal from morphine was expedited and his transition to oral mediation was done at a faster rate that normal and we are hoping to be discharged tomorrow, Day +19.

Treatment update 9th September 2012

Ryan has been admitted to the KMT Unit in Station 16 of University Children's Hospital, Tubingen.  He has settled in his room in isolation which will be his home for the next 8-12+ weeks.  His treatment started with a a test dose of ATG which is used to destroy Ryan's T cells in preparation for the transplant, providing the test dose does not cause severe problems Ryan will then receive 3 days of the drug at full dose.  The main side effect of his is severe allergic reactions ranging from high fever, to heart and breathing problems.   On the test dose and first full dose of ATG Ryan did experience high fevers, high pulse and low blood pressure and was in need of platelet and blood transfusions but after this the side effects improved. Treatment starts on Day -12 and counts down to Day 0 being the day that Ryan receives my stem cells.

Treatment update 20th August 2012

Ryan underwent a multitude of tests and investigations in preparation for the haply-identical transplant and with the exception of an MIBG scan all were kindly performed by our local hospital in Exeter who bent over backwards to do these tests in a way that kept Ryan out of hospital as much as possible during his last weeks before travelling to Germany.

The scans confirmed that Ryan remained in full remission, his bone marrow was received and processed in Vienna and that is also completely clear.  This puts Ryan in the best possible position for the treatment ahead.

We received communication from the consultant in Tubingen that there was to be a change of plan and I was to be the donor of stem cells instead of Gareth, despite the fact that I had anti-bodies to a virus in my blood.  The reason for this was that I am a 7-8/10 match to Ryan's bone marrow whereas parents are usually approx 5/10 and this may reduce the chance of Ryan's body rejecting my stem cells.  I will start a 5 days course of injections on the 13th -17th September in preparation for the stem cell harvest.

There will be a period of time that Ryan will have no treatment before travelling to Germany and in that time we hope to keep him fit and well.

Treatment update 29th July 2012

Ryan’s blood counts struggled to recover from the 2nd cycle of chemotherapy and so he started the third cycle 2 weeks late.  His platelets are never above 100 and so these are discounted for the purposes of chemo but his neutrophils need to be above 1.0 before he can start another cycle of treatment.  The reason that Ryan needs chemotherapy is because he cannot yet be accepted for Treatment in Germany now.  His consultants were concerned that is we continued with chemotherapy Ryan may become Aplastic, which would mean that his bone marrow would fail completely, leaving him totally dependent on blood products and with no means of fighting infection – this had happened to a child in a similar situation to Ryan and so his consultants were very aware of the severity of the situation that Ryan could be in.  We discussed the option of stopping chemotherapy altogether, as no one can be sure that there is a need for on-going treatment, but decided that the safest decision would be continue chemotherapy but to change to a different regime; one that is less toxic to the bone marrow. 

And so on the 18th June Ryan was started on a combination of vincristine and temozolomide.  The vincristine is given as a slow push from a syringe into his hickman line and the temozolomide is given as an hour and a half infusion.  The main side effects of vincristine are nerve pain and bone pain, especially effecting the jaw, back and legs and the effects of temozolomide are nausea, sickness, diarrhoea, hair loss and general tiredness.

Ryan tolerated the new combination of treatment quite well, he did feel very sick most mornings during the week of treatment and couldn’t eat breakfast and generally wasn’t hungry but by the following week this improved and his appetite returned to normal.  He did suffer with back and jaw pain and his hair is very slowly falling out and so we gave him a grade 2, which he didn’t mind too much as we had intentionally kept his hair quite short since starting chemo in March.

The chemo had the desired effect on his bone marrow and his neutrophil count was sufficient for him to start the 4th cycle of the new combination on the 16th July 2012.  This time we gave him more anti-sickness from the start of treatment and woke him during the night as well so that when he woke up he was still covered by the medicine.  This worked much better for him and he felt much better than previously and even ate breakfast normally.  He didn’t suffer with pain this time but his hair is now almost gone, which he is not particularly pleased about, although luckily none of his friends have paid any attention to this.

On the 11th June Gareth and I had a meeting in Tuebingen with Dr Peter Lang.  The centre in Tuebingen have been treating children with Halpoidentical transplant for 15 years, but only much more recently with this regime for Neuroblastoma. 

Dr Lange talked through the treatment and the risks and side effects involved; Ryan will be admitted to hospital on arrival and start a regime of drugs, Anti-Thymocyte Globulin, Melphalan, ThioTEPA and Fludarabine designed to destroy his bone marrow. He will receive these drugs over a period of 11 days then there will one day’s break before he receives Gareth’s stem cells.

The stem cells will have been collected from Gareth in the couple days prior to Ryan receiving them, they will be prepared in the laboratory and T & B cells will be removed but Natural Killer cells will remain. 

The new stem cells will take approximately 12-15 days to graft in Ryan’s bone marrow and it will take approx 2-3 weeks from this time for count recovery.  Ryan would remain in the transplant unit for a minimum of 6-8 weeks after transplant.  All of these timescales are approximate and an average based on previous patients, the timescales could be much longer should there be complications such as infection.

In the period after Ryan has received the high dose chemotherapy and before the new stem cells he will be at great risk of infection, which can be fatal, as his immune system will have been totally destroyed.  For this reason he will be in isolation.  Gareth and I will be allowed to visit him but there are strict rules to follow for example all of Ryan’s clothes have to be washed at 60 degrees and tumble dryed on high to kill any bacteria, he has to follow a ‘clean’ diet – which means his diet will be very limited, any toys or items taken into the room must be new, the packaging to be removed just before entering the room, or if not new must to thoroughly cleaned with an alcohol wipe.  The rules are extreme but are there for Ryan’s protection.  We remember from last time that after a period of time the rules become second nature but that doesn’t make them any easier to explain to Ryan.

In this period he will also have mucusitis, this is a condition caused by the chemotherapy destroying the lining of the mouth and stomach – this happens because chemotherapy targets rapidly renewing cells – cancer cells – but cannot differentiate between the normal rapidly growing cells such as those in the mouth and gut.  Mucusitis of this severity is horrendous, Ryan will be very poorly and during this time we expect Ryan to need a continuous infusion of morphine due to the pain that this will cause.  The morphine in itself also causes problems effecting breathing, blood pressure and gut function.  Ryan will obviously not be able to eat during this period and will receive IV nutrition, TPN, to give him essential fluid and nutrients and to try and counteract the weight loss although in our experience we know that Ryan will lose a lot of weight. Weight that he unfortunately cannot afford to lose.  He will receive a multitude of preventative drugs during this period to try and protect Ryan from infection; he will receive anti-fungal medication, anti-viral medication and anti-biotics.  There are so many drugs to give that they are non-stop, throughout the day and night, it is very hard to keep track of what drugs he is having and when they are due.  I always like to know what Ryan is being given and why and when it’s due, it is something that I can control but in this situation before I remember losing that control.

The chemotherapy can also cause temporary, but life threatening, damage to his heart, liver and renal function.  It can also affect hormone production, thyroid function and growth later in life, in addition to infertility.  Another risk of the transplant is Graft Verus Host Disease (GVHD) This is a condition caused by the donor stem cells attacking the organs of the host. This can effect the skin, liver and gut.  If acute it will be seen on the first week after transplant but chronic cases can appear as late as 100 days after transplant.  Statistics so far show that 4% of patients experience grade 3-4 GVHD and 20% suffer with Grade 2 GVHD.  To try and counteract GVHD Ryan will be given an immune suppressant for 30-40 days after transplant.  I have written the above based on the notes I made during our meeting but cannot be 100% sure of my facts at this point in time.

We hope and pray that Ryan’s pain will be controlled, that the care that he receives is first class and that he does not get any complications.  Ryan will be admitted for treatment on the 4th September, 2 days after his 6th birthday.

In the next few weeks he will undergo a series of tests and investigations.

Treatment update 7th June 2012

On the 3rd May we finally heard that Ryan bone marrow trephines were clear – there we no neuroblastoma cells present in the sample taken for analysis – a fantastic result as there was always the worry that during radiotherapy, which only targeted the tumour, the disease could have been progressing elsewhere.

On the 16th May Ryan had an MIBG scan at Bristol Children’s Hospital; this involves him being injected with a radioactive dye the day before the scan and then lying under a scanner without moving for approximately an hour.  There are 4 or 5 images taken and each one takes 10 minutes so he can stretch briefly between images but it is still a long time. 



Then on the 17th June back in Exeter hospital Ryan had an MRI scan.  The MRI scan is very noisy and you have to wear head phones whilst inside the machine and so Ryan choose one of his favourite CD’s.  The scan took just over an hour in total and several times Ryan was required to hold his breath for what felt to me like an awfully long time!  He did really well and didn’t move.



On the 21st May we learnt that Ryan’s MIBG scan was clear – there were no neuroblastoma cells taking up the radioactive dye.  This meant that the tumour had died but did not give us any detail.  We still needed to know how big the residual tumour was and if Ryan would need surgery.



On Thursday 24th May we had the astonishing news that there was no sign of the tumour visible on the MRI scan.  The tumour had gone, there was no need for surgery.  This was a result better than we had ever hoped for and meant that Ryan had achieved a full remission – there was no evidence of disease in his body or bone marrow.


Unfortunately this doesn’t mean that he is cured, after all we have been lucky enough to have been in this position before, twice.  This doesn’t mean that there are no cancer cells but just means that to the best of the technology available there is no visible sign of cancer. Unfortunately neuroblastoma has the ability to remain dormant in the body only to be triggered, months or years later, to grow again.  It only takes one cells to be left behind.  And so our decision to take Ryan to Tubingen for a haplo-identical transplant is not changed.  We have a meeting with the consultant a the clinic in Germany on Monday 11th June to discuss the treatment in detail.

We are hoping that this treatment will give Ryan a new immune system, one that is capable of identifying and destroying any remaining cancer cells and one that is strong, unlike his own very weak bone marrow.

On the 31st May Ryan had a synacthen test.  Ryan was injected with a synthetic form of the hormone released by the pituitary gland and then blood taken at regular intervals to see if his body could respond appropriately by producing cortisone.  Unfortunately Ryan failed to respond and so he continues to need hydrocortisone 3 times daily. 

Ryan has tolerated the chemotherapy regime well, with manageable diarrhoea.  However his bone marrow has not recovered following the 2nd cycle of chemo, meaning he is dependant on blood products, and so the 3rd cycle was delayed by one week.  But looking at his blood counts today it isn’t even looking promising for next week either.

Treatment update 30th April 2012

Ryan completed his radiotherapy on 5th April, the day of his stem cell harvest.  However the effects of radiotherapy will continue for a further three weeks.  The main side effects are a cough caused by irritation to the lungs, a sore throat, red sore skin and tiredness.  We have been very fortunate, Ryan has a mild cough in the evenings but nothing that is bothering him.

As radiotherapy can cause inflammation at the site of the tumour and we could not afford for the tumour to swell even 1 mm due to it pressing on Ryan’s spinal cord, Ryan was started on Dexamethasone, a steroid, to prevent inflammation.  This did it’s job but one of the side effects, apart from increased appetite which we did not complain about, was that it can cause the body to stop producing cortisone, a steroid hormone released by the adrenal gland. It can then take weeks or even months for the body to adjust and start producing the hormone again itself.  Unfortunately Ryan has suffered this side effect and his adrenal gland has stopped producing cortisone and so he needs to have cortisone 3 times a day. If he was to become unwell with an illness or has an accident his body would normally release higher levels of cortisone to enable him to effectively mount a response but in that situation without being able to produce his own cortisone Ryan could become seriously ill.  We therefore have to carry a syringe and vial of cortisone so that we can give him an injection should be become very unwell.  Just one more thing to worry about eh!

On the 16th April he started a combination of temozolomide and irinotecan.  This involves 5 days of chemotherapy; one chemo is oral and means Ryan has to swallow 5 capsules each morning on an empty stomach and then one hour later has to be connected to the other chemo which is an hour infusion.  The most common side effect of this treatment is severe diarrhoea, sickness, nausea, low blood counts and hair loss.  To date Ryan is tolerating the treatment well.  The treatment cycle is 21 days and so next week Ryan starts the 2nd cycle of treatment.

Ryan is receiving chemotherapy as a precaution as we do not know the effect of the radiotherapy on the tumour, he cannot have an MRI until the inflammation has gone which they anticipated to be 6 weeks after the end of radiotherapy.  The other reason is if, in the period of radiotherapy, Ryan has developed disease elsewhere in his body the chemotherapy should slow it’s progression.  He is due to be re-staged in mid May and we hope and pray that we get some good results.

In the background Ryan’s lead consultant in Bristol has been in contact with consultants in London and has also spoken to the Consultant in Tubingen, where the halo-identical transplant would take place.  He has now had the opportunity to discuss some of the questions that he had regarding the treatment and, although he still has some things he wishes to clarify, has confirmed that he is happy to support us if we choose to take Ryan down this route.  He commented that the approach in Germany seems to be the only systematic approach being looked at, and that very importantly, does not suggest that patients are being harmed by the therapy.  This is very reassuring as although we could have taken Ryan to Germany independently we much prefer to do this with the knowledge and support of our UK consultants behind us.

We are currently awaiting results of the bone marrow trephines (a cylindrical core of bone) taken on 13th April.  Unfortunately the bone marrow aspirates (the fluid part of the marrow) which were sent to Vienna were not able to be processed due to a problem with the storage of the samples.


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