MS: Busting the Myths
February 9, 2022 | Life with MS, Treatments
My name is Anne Besley. I am a 51-year-old mum, wife, daughter, sister, friend and registered nurse and in a past life a registered nurse. I live in West Auckland. Originally hailing from Africa (born in Zambia, raised in South Africa) New Zealand is where I have had all of my adult life and I absolutely love it here. I was diagnosed with remitting relapsing MS (RRMS – Remitting Relapsing MS) in 2006. I have a great family, and many wonderful and special friends, all very supportive of me. I am truly honoured and blessed to know these people and have the family that I have. I feel like I have my very own cheerleading squad! I surround myself with positive, warm, caring people. I also believe that my positivity attracts positive people.
Tysabri was the 4th disease modifying drug (DMD) I had been on. In May 2019 I tested positive for the John Cunningham Virus (JCV) after 2 years of being negative. Tysabri is a great DMD, and of all the drugs is one of the drugs that has the highest chance of controlling remitting relapsing MS. However, it comes with some serious risks. After two years of being on Tysabri, I tested positive for the John Cunningham Virus (JCV) with a high viral loading, and was told I had a 1:333 chance of developing the almost always fatal brain infection Progressive Multifocal Leukoencephalopathy (PML), and this risk would climb with each infusion of Tysabri I had. I was unbelievably frightened.
Tysabri works by preventing the white blood cells responsible for attacking the myelin from breaching the Blood Brain Barrier. If you are negative for JCV, you have a 1:10,000 chance of contracting PML. If you are positive, your risk leaps up to 1:333 and each infusion you have that risk climbs. Eventually, my risk would become a 1:125 chance of contracting this infection.
The analogy my husband came up with to explain the risk to our friends was apt. If you swim in the ocean, you know that there are sharks out there. You know your risk is tiny, miniscule, maybe a 1:10,000 chance that a shark will attack you. But suddenly, something changes and this risk goes up; you see some fins and know that there are 333 sharks in the area. They are quite some way away, and they have some barriers preventing them from getting to you, but there is still a chance one could swim through. Will one of these sharks get past the barriers and bite you? And, will that bite prove fatal or will you be lucky enough to survive it? And how disabled would you be after the bite (PML causes quite profound disability)? This is what it was like for me when I was told I had suddenly seroconverted to JCV positive. Sometimes being a nurse is a good thing, but sometimes I truly think the saying ‘ignorance is bliss’ has a place!
Even though I was reassured by my neurologist that they would keep a close eye on me, I still could not reconcile with the fact that if I contracted PML, and even if it was caught very early, and in the best-case scenario, I didn’t end up too badly brain-damaged or disabled that I could no longer receive any of the other Disease Modifying Drugs to prevent the MS progressing except Copaxone. Copaxone was the second DMD I went on and proved to the be the least effective. This was a risk I was simply not willing to take, no matter how closely I was monitored.
I had a frank conversation with my neurologist about a procedure called HSCT (Haematopoietic Stem Cell Transplantation). As this is not a procedure performed by neurologists, my neurologist could not comment on it in depth. HSCT is a procedure that has been performed on blood and bone marrow cancers since the 1960’s. In the 90s this procedure was tested on mice with simulated MS with encouraging results. Since then, there have been numerous randomised controlled trials to test for the efficacy of HSCT concerning treating MS.
After some lengthy discussions with family, friends and my neurologist, I decided this was the way forward for me. My neurologist referred me to a haematologist so I could pose some questions to him relating directly to HSCT. If you are a person looking to have HSCT, I cannot recommend visiting a haematologist highly enough. I recommend a discussion with a haematologist who performs HSCT and Bone Marrow Transplants if possible. HSCT is in the domain of Haematology, not Neurology. There are questions about the procedure that needs to be directed at a haematologist who specialises in HSCT.
There are many support groups on Social Media platforms like Facebook, and whilst these are informative, they are limited in that these are people who have had or are considering HSCT, but none of them is a haematologist. I was alarmed at the medical advice being given on some of these sites, and some of it was misinformation. The HSCT protocol for MS and other autoimmune disorders came out of the MIST trial, the first international large-scale randomised trial into autologous haematopoietic stem cell transplantation (HSCT) in remitting relapsing multiple sclerosis. A breakdown of the MIST trial can be read on the Neurology.org website.
HSCT is not performed in many countries yet and patients are travelling to countries where it is offered. When you return to your home country, you will need to support and follow up of medical practitioners who understand HSCT concerning the treatment of MS. It makes sense to me that you have the backup and support of a haematologist familiar with this procedure. HSCT is not a procedure to be taken lightly, it comes with some significant risks.
Many neurologists are still resistant to discuss this procedure, but you will still need the support of your neurologist post HSCT. I am very lucky my neurologist is a practitioner who is open to having this discussion, so I was referred to a haematologist to ask those important questions. If you find you have a neurologist who is resistant, find the evidence that HSCT is a procedure used to treat MS, and take that evidence to your neurologist and ask them to read the literature. When I say evidence though, I mean the scientific papers. They are not going to be swayed by here-say accounts, or by anything that isn’t backed by science. I will provide some links in the links chapter of this book. If the neurologist is still resistant, and you are determined to look into HSCT, then perhaps find a neurologist who is happy to have the conversation.
Before committing to HSCT, please do your homework, I cannot stress this enough. There is so much to know and understand and this is a decision not to be made lightly.
In the end, I decided to have HSCT. I felt I had no other options available to me. The drug Ocrevus (Ocrelizumab) was not yet available in New Zealand (it is now available for some people).
The research I did on HSCT showed me that this procedure has the best chance of putting the MS into remission, better than Tysabri and Ocrevus. But please don’t think that HSCT is a cure, it isn’t. HSCT aims to achieve remission that is all. It cannot cure MS or any other autoimmune disease.
Some people don’t respond to HSCT (non-responder), and certain things make this procedure less successful. If you have remitting relapsing MS, with a low EDSS, have not been on Disease-Modifying Drugs and have active MS, HSCT is much more likely to work well for you. The progressive forms of MS don’t respond as well, and the higher your EDSS, the more likely you are to have progressive MS and the less chance HSCT less of working well. Also, the more Disease Modifying Drugs you have been on the less likely it is to work for you. But, please note that some people who have progressive MS have responded very well and there are people with remitting relapsing MS who are non-responders.
Once I had made the decision, I was frightened, excited and daunted in equal measure. Frightened because this is not a procedure without significant risk. Excited at the prospect of getting a new immune system – how many times had I written on my Facebook status around Christmas time ‘All I want for Christmas is a new immune system’. I would need to travel overseas for this procedure and how was I going to raise the money for it? And where could I go? I may not fit the entry criteria: 50 or under (I was almost 50), have active MS (my MS was stable on the Tysabri so no recent lesions) and have an EDSS under 5.0 (mine was 2.5 thanks to the Tysabri) I had also been on 4 different Disease-Modifying Drugs, so that also went against me a little.
I chose India for several reasons; they charge the same as it costs for the Government in New Zealand to fund someone to have HSCT for cancer which is about $40,000NZD. With the exchange rate, I was charged $42,000 and this cost included my support person’s food and accommodation (they stay in isolation with you) and our transfers to and from the hospital. (India asks for you to take a support person and I must say that I could not have coped without my support person which was my husband Brett – your support person is not there to provide nursing support, but moral support for you). After filling in some forms, and speaking directly to the Haematologist in India, I was accepted for treatment at the Apollo Hospital in New Delhi.
Now all I had to do was raise the money. I set up a crowd-funding page. This was a very difficult thing to do, I loathed asking for money from people. Each time I accepted a donation I felt uneasy, but I was so grateful for the help given to me. I was lucky enough to be called by a reporter for the online news site Stuff.co.nz who ran a story on me. So many people donated to me, I was beyond humbled. I asked a few of my friends to help me with fundraising ideas. These lovely ladies kept my sanity and came up with some amazing ideas and fundraising prizes. A very good family friend Kirsty and her mum Marjory set up a fabulous quiz night. They wouldn’t allow me to help in any way. Kirsty wrote the whole quiz herself. She is an amazing lady whose attention to detail can’t be faulted. Some friends and some strangers donated the most amazing prizes for the live and silent auctions. The night raised a massive $10,000! I was also eligible to access my KiwiSaver fund on both requirements because the Tysabri had threatened my life and without treatment, it was a sure slide into permanent disability. With all of the help I had, I was able to raise enough for the treatment, the flights for myself and Brett my husband, medical insurance and a small buffer in the event I needed to stay longer. All of this was done in an unbelievable 9 weeks!
We flew out on the 19th of October 2019. It was not a moment too soon because by this stage I had been off the Tysabri for almost four months, and the MS was firing some warning signs at me. We arrived in New Delhi a day later and transferred straight to the Hospital. I was booked in there under Dr Gaurav Kharya who is the Clinical Lead and Senior Consultant Haematologist for the Centre for Bone Marrow Transplant and Cellular Therapy at the Indraprastha Apollo Hospital. We arrived in New Delhi and were met by a representative who got us through the busy airport quickly. I highly recommend to anyone flying overseas for this procedure to get wheelchair assist at the airports, both ways, even if you usually walk well. It saved my legs in those massive airports and got me through lines so much more quickly.
It is expected you will be there a month. The first two weeks is where everything happens (pre-tests, stem cell liberation, stem cell harvest, chemo, and stem cell re-infusion) the last two weeks are for observation, and to correct any issues arising from your bone marrow being ablated.
On the day we arrived, the pre-tests started in the afternoon. I went for a lung function test and an ECHO of the heart and over the next few days an MRI, a CT scan, a Kidney X-Ray, not to mention blood and urine tests. I was examined by a neurologist. Once it was determined I was fit enough for the procedure and met the criteria, we had an in-depth consultation with the Dr Kharya (who all his patients call Gr G) and his team where all of the risks were discussed, the benefits vs risks, what to expect, and was invited to ask any questions. I must tell you it was confronting signing the consent form after reading the risks.
The following day I was given a drug called G-CSF which liberates the stem cells from the bone marrow in the blood. I was given this drug for 4 days, and the side effect of this drug for me was bone aches.
I was then moved from the ward to the Bone Marrow Transplant (BMT) Unit into isolation. The very next day was the stem cell harvest. The eagle-eyed Dr G noticed the great big veins in both of my arms and asked if I was happy for them to be used instead of a vein in my neck. There is less risk of infection using the arm veins. The downside is I had to lie with my arms straight and still by my side for 7 hours and was not allowed to move them. The way the stems cells are harvested is with a machine that collects your blood from one vein, the blood is spun down with a centrifuge and the stem cells are separated and collected in a bag, and the blood is returned to you in the other vein. After 7 hours my precious stem cells were collected, and blood bank came up to collect them, preserve them and cryo-freeze them.
That afternoon I had a PICC (peripherally inserted central catheter) line inserted into a vein in my upper arm just below my axilla (armpit) and this would remain for the rest of my stay. It is used to administer the chemo, to give IV fluids, take blood for blood tests, administer IV antibiotics and medications and blood products if needed.
Dr G follows the non-myeloablative protocol using a combination of cyclophosphamide and ATG. The chemo started the evening of the stem cell harvest. I remember the symptoms of nausea and weakness coming on within just a couple of hours of the chemo commencing but I was given lots of anti-nausea medication. Cyclophosphamide is excreted by the kidneys, and they flush you with an enormous volume of IV fluids to flush it out. This drug aims to suppress the immune system, and it works by eliminating the T and B white cells. These are the white blood cells implicated in attacking the myelin in MS.
The next three days saw me have more cyclophosphamide, many more bags of IV fluids (these did not stop for about 8 days) and the introduction of the drug ATG. (Anti-thymocyte globulin) is an infusion of horse or rabbit-derived antibodies against human T cells, a big culprit in attacking the myelin sheath. Dr G uses rabbit ATG, because it stays in the body for at ;east a month and will kill any rogue T cells if there were any in the stem cells when these are given back to you.
I honestly don’t remember too much about these following three days. The whole procedure was a blur, a veritable chemo blur. I did get some side effects after starting the ATG and Cyclophosphamide, some blood in the urine which they swiftly dealt with, and a rash from the ATG, again swiftly dealt with. I do remember on day two and three having to dig very deeply because the chemo had made me feel so very ill. I was unable to eat anything. My taste changed to a nasty metallic taste.
After the chemo regime was completed, my blood was tested again, and I had zero detectable leukocytes (white blood cells). Mission accomplished! That afternoon, they defrosted my precious stem cells and transfused them back to me. The whole team gathered again, and quietly said a prayer for me. I am not a religious person by any means, but I was very humbled. It was done in silence, and very respectfully.
I had been warned that reinfusion could cause issues, as the preservative can cause reactions. Again, I was flushed with a huge amount of IV fluids and encouraged to drink lots of oral fluids. I was also warned I would taste a weird taste, and that this would come through my skin pores. It tasted like an odd citrus taste, and this was the smell that my husband said he could smell. I also developed a heavy feeling in my chest, which was quite uncomfortable, but soon passed after they had finished giving me back the stem cells. When you think about the process of receiving the stem cells back, it is quite humbling. These cells are not delivered directly to the bone marrow but are given via the bloodstream and they know exactly where to go! ‘Homing in’ usually happens within the first hour, sometimes as quickly as twenty to thirty minutes. When you think about it, this is quite amazing!
Now we had to wait to see what, if any side effects would need rectifying post-chemo. You are very closely monitored for infection. At the slightest indication of a rise in temperature, I was given IV antibiotics on top of the ones I was already receiving, and IV paracetamol to bring down the fever, and blood cultures were drawn to make sure the spike was not an infection. None of the temperature spikes was related to infection, and after a while, it was safe to determine that I was having engraftment fevers. These are good fevers, in that it indicates the stem cells were beginning to make new red and white blood cells and platelets. I was given a granulation infusion from a donor with the same blood group as me. Granulocytes are a category of white blood cell (comprising of eosinophils, basophils, and mast cells) that would give me some immunity, but not the autoreactive T and B white blood cells, which are leukocytes.
Over the next two weeks, I was given several platelet transfusions as my platelets were very low and I received potassium infusions. I had to drink electrolyte drinks. I forced myself to eat. This was hard as I still felt quite nauseated, and had that metallic taste in my mouth. 5 days before we were due to fly home, I developed serum sickness, a reaction to the drug ATG. Serum Sickness is similar to an allergy. The joint and muscle pain were quite unbelievable, my husband had to almost lift me in and out of bed. I found these joint and muscle pains crippling and they lasted for some weeks. When the Serum Sickness started, I developed a high fever and a few hours later the tell-tale rash. I was given medications to combat the side effects, and most importantly steroids.
This has been an experience I will never forget, and I am glad I did it. Has it worked? It is far too early to say. I only received my stem cells back on the 30th October, so feel commenting right now would be premature. I think I could only judge in 6-12 months to say. I have to have 2 follow up MRI’s of the brain and spinal cord to see if there is any change on the MRI and ensure there has been no progression.
I may still suffer further relapses or progression. HSCT is not a cure. This procedure can’t heal the damage already done, and I may still suffer issues and symptoms from the damage to the myelin from previous attacks. But I am accepting of this. All I want to achieve is a permanent remission.
Many people who have had HSCT do report an improvement. I am not counting on that, but if there is an improvement that would be most excellent! The new exciting medical term is ‘Stem cells’ and it is associated with some kind of magic. I can’t speak for any other procedures using stem cells, but it is the chemotherapy that is the backbone of HSCT for autoimmune illnesses. It is the ablation of the bone marrow targeting the autoreactive T and B white blood cells that halts the MS. The stem cells don’t go to the myelin sheath and heal it, these stem cells are to repopulate the ablated bone marrow after the chemo and give you a new immune system.
Before you commit to travelling overseas for HSCT, understand that there is a 6-12 month recovery period, and from what I have read and from the people I have spoken to for personal accounts, they assure me it is more like a 12 month recovery period. You need to be prepared for this. You are in this for the long game. It isn’t just a simple case of popping overseas for a quick procedure. Your bone marrow will be ablated and then ‘regrown’, and this recovery phase must not be underestimated. These 12 months are commonly known as the HSCT rollercoaster phase. I have been home for less than 10 short weeks, and am seeing this already. There are 3 months where you need to be on a neutropenic diet, which needs pre-planning and thought. You can’t eat any fresh fruit and vegetable, and you can only eat fresh dairy that is pasteurised. You can’t eat left-overs, all food must be freshly prepared for each meal. Takeaway meals are off the table for months. Depending on the centre you go to for treatment, they may or may not require you to be re-immunised. This procedure may wipe out all previous immunity and vaccinations.
You will need to think about possible complications post-treatment. Do you have a haematologist who can look after you, and what does your GP know about the procedure? Will there be someone available to take you to the doctor if you need to visit? Will there be someone at home to help you out for a while. I was very lucky in that I bounced back quite quickly in terms of energy, but others I know who have had this weren’t so lucky for a couple of months or more. I have had two lots of antibiotics since returning home; my daughter came home from school with a cold, and despite best efforts (wearing N95 masks, hand washing, staying in different rooms as much as possible, etc) I developed the beginnings of a chest infection, and then a sinus infection with an awful cough.
The centre where you go from treatment will want to know about follow up blood tests, neurology visits, and MRI results. They will send you home with a schedule most likely. I have to see my neurologist at 1, 3, 6, 9 and 12 months for an assessment. They have asked for 2 full MRIs (brain and spinal cord) at 6 and 12 months and regular blood tests. They rely on you to get these reports done so they can track your progress.
A lot of preparation needs to go into this, and robust research and support is an absolute must.
The care I received in India was absolutely excellent. I don’t think there was anything I could have thrown at Dr G and his team that they couldn’t sort out. As a nurse (and my husband is an anaesthetic technician) I was so happy with the level of care I received.
2 years on I am very happy that I went for HSCT – it has been an absolute game changer for me – I can walk so much better, I no longer suffer from the bone-crushing fatigue so common in MS, my pain is under much better control, and so many of my symptoms have improved…! I do feel it needs to be made available in NZ as it was very stressful to have to fundraise all of that money and head overseas to have this life changing procedure. We already do it here for blood and bone marrow cancers, so with funding the service should be extended. I am no longer drawing on the monthly cost of the DMD’s I was on – these costs amount to thousands of dollars per person per year. I am back at work and a tax payer again. The stress on my then 25-year-old daughter was immense – she understood that HSCT is a risky procedure and it was horrible for her to have to wonder for a month how I was. I also flew back to NZ during a measles outbreak which terrified me as my immune system had been ablated and 1 month after the World Health Organisation announced there was global pandemic (Covid). This procedure has so much robust scientific evidence supporting it as the best procedure for my form of MS (RRMS), and it often has positive outcomes for the progressive forms of MS too.
My wonderful Mum has since started a petition to try and get aHSCT available here in New Zealand for MS patients. Please take a moment to sign this petition.
If you want to make contact with me to chat about India, please don’t hesitate to send me an email – devsmum04@gmail.com.
Thank you.
Photos:
My hair…..going, going gone! Stem Cell Harvest
My precious Stem Cells
The harsh realities of chemo
Stem Cell re-infusion The wonderful BMT Team.
(Dr G is hiding in the back – he is wearing glasses)
Studies and trials for Autologous HSCT:
https://clinicaltrials.gov/ct2/show/NCT03342638
https://jamanetwork.com/journals/jamaneurology/article-abstract/788580
https://www.sciencedirect.com/science/article/abs/pii/S1474442209700171
https://www.mathec.com/wp-content/uploads/2019/07/JAMA-MS-2019.pdf