Nikhil Autar

Tag: bone marrow transplant

  • Bone Marrow Transplants – The ENTIRE Process. How They Work. A Patient Guide and Story.

    Bone Marrow Transplants – The ENTIRE Process. How They Work. A Patient Guide and Story.

    Bone Marrow Transplants are scary. And they’re a unique procedure whose impacts can last longer than many regular organ transplants. But they also save lives. I’ve had 2 myself. Both were allogeneic transplants, the focus of this blog post, which is where you receive your cells from a donor. I’m a medical student and tumor vaccine researcher, but I wrote this out to outline the process for a fellow patient recently – so it’s in plain English – and it’s also more patient focused. I found, personally, that a fellow patients’ words just stuck more. So I thought I’d share it with you. This isn’t medical advice, and every patient is different – so ASK YOUR DOCTORS ABOUT YOU! But it’s hopefully a mixture of reliable information + experience. I hope it helps. Feel free to reach out (there’s a contact button on the website – or messsage me on my Facebook page where I’m most active – or Instagram).

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    Bone Marrow Transplants

    The bone marrow transplant procedure, in a nutshell, is basically getting someone else’s blood stem cells (haematopoiec stem cells is the technical name), located in their marrow, and infusing it into you, so it settles. They aim to get someone else’s immune cells in you, to kill off your cancer (your immune cells are made by your blood stem cells). And the major side effect, other than the dangerous infections you can get during the procedure and in the first 30 days due to, largely, chemo, is graft versus host disease, which can last a long time in others (but in small doses, is actually a good sign the process is working).

    How it works for the donor – it’s taken peripherally from the arm, after getting a medicine which makes those stem cells enter your circulating blood for a few weeks (click here to learn about that).

    On the recipient’s end, you receive it through an infusion into your veins, in most all cases. It eventually finds it way into your marrow and starts producing your donor’s blood cells (including white, immune cells), after a few weeks (it took 3 weeks for mine to engraft on both occasions, but it can vary).

     

     

    The idea is, though you and your donor are matched as well as you can be – there will always be slight differences between you and them, which makes them recognise cancerous cells and kill them off, where your immune system may have lost the ability to do. This is a good thing in that it’s how the BMT or SCT (stem cell transplant) is supposed to work. But it also is the cause of the major side effect, graft versus host disease, where your donor’s cells attack your own organs. I’ll get to that later, here’s how it all goes though.

     

    Prior to the transplant, you receive workup of some kind – often they want to ensure your underlying disease is under control. If it’s a blood cancer, often that will involve chemotherapy. Once they have the disease and any underlying conditions mostly under control, and they find a match, and coordinate timings (usually, you want to get the donor’s cells into you as soon as it’s taken from them), they begin the workup to the actual stem cell transplant process.

     

    Usually, a week or so before, they’ll begin immunosuppressive regimens and chemotherapy that are designed to kill off your current immune cells. In younger patients, they may also offer total body irradiation, which is a high dose of radiation given to your entire body (in younger people, marrow can be produced all over the body, so all areas are targeted, though they will provide shielding to your brain and lungs, in most cases). The idea is to kill off your old bone marrow’s cells and replace them with your donors’.

     

    I won’t lie, the BMT process and chemotherapy is tough. But it is lifesaving. Definitely listen to your doctors!

     

    During the next few weeks, like many chemos, you will have a lot of your immune cells and your blood cells obliterated. So you’ll be very susceptible to infections. It is very important to do everything you can to avoid infections in this time, from limiting visitors (especially sick ones), to cleaning and bathing regularly (even when you won’t feel like it) and following your doctors’/nurses’ orders. You also may experience other side effects such as nausea, gut pain (from your stomach lining cells dying off), fatigue and general unwellness. There are many chemotherapy specific side effects too that may occur, and you may also get other side effects – eg. with TBI (total body irradiation), you often get mucositis – inflammation of your mouth and throat – which can be extremely painful. I’ve personally experienced this myself and highly recommend you follow doctors’ suggestions and get ENG tubes if they think it’s appropriate and helpful, and getting pain teams to come in and help too. Having said that – my second transplant was a ‘reduced intensity chemotherapy’ regimen. I only had nausea and didn’t get an infection once, and it went quite smoothly compared to the first. Everyone’s different, every regime is different, and even in one person, at different time points, you can react differently.

    Other things they may do in your workup/the month before your transplant, is check your heart, and lungs, and, if you’re in that age category, your fertility. They’ll put a line in just before they begin treatment in hospital, this may be in your arms, or via ports they put into your neck. During the transplant, and the immediate transplant workup, they’ll watch over you, do bloods regularly, get scans when required, and treat things like infections. Infections are often the most dangerous thing you may face, but they’ll be sure to give you antibiotics, and other treatments, as required during this time frame.

    This is the TBI – total body irradiation process. This is usually done in younger patients, as they are more likely to have marrow that persists in other bones of your body (adults often only have it in their sternum and hip bones). Hence why they shoot radiation at your entire body (left of this photo is a machine which does this). The rice bags keep you still and provide some protection to important organs like your brain and lungs. And they keep you still. It lasted 30 minutes, and I had 5 sessions over a week at a special clinic the week before my transplant). Straight after you may get a burning sensation in the skin (this is resolved by creame in most cases). The other common side effect is mucositis, a sore throat, which can be very painful. So listen to your doctors if they recommend a feeding tube! I learned that the hard way!

     

     

    At some point, often 3 – 4 weeks after “Day 0,” where they infuse you with your donor’s cells, you’ll ‘engraft’ and have your donors’ cells start making cells in your blood. They’ll be monitoring for this. After this, a good number of people get acute graft versus host disease, which can affect any of your organs, and can be pretty severe. This occurs in the first 90 days usually, and can affect any of your organs – from your skin, to eyes, to liver, to gut. I personally had bad skin and liver and gut GVHD (in my first transplant, I had skin and liver aGVHD, and in the second, liver and gut aGVHD). Not everyone gets GVHD. It can be a good sign that you’re getting the ‘graft versus disease’ effect too (where your donor’s cells kill off/stop your cancer cells from returning), but too much GVHD can be bad too. Your doctors will treat you after you engraft with some medicines that suppress your immune system – often cyclosporine, but different doctors/patients use different treatments. If GVHD manifests and gets severe, they may add more or increase your dose. Or they may reduce them over time.

     

    You’re still not out of the woods after this time frame. You can get infections, still. And with GVHD – days can be critical when it comes to your outcomes, so make sure you tell them of anything you may experience. With different organs, you may experience different signs. Eg – with the skin, you may get rashes or feel like your skin is burning. With the gut, you may get diarrhoea, sometimes constipation. With the eyes, you may get burning or find it difficult to open your eyes (which may be due to skin GVHD affecting the skin around your eyes). It varies from person to person. It’s VERY important you see your doctors if something happens. But sometimes, you won’t feel anything. With my liver graft versus host, I didn’t feel a thing, but had very very high liver enzyme tests.

    I couldn’t find a clean, clear photo of my skin, so sorry for the captions. But this is chronic skin GVHD – I have quite severe chronic GVHD and it’s not too bad, other than the looks (I don’t mind the looks though – this is how I dealt with the social anxiety that comes to many post transplant, due to the change in looks). Acute skin GVHD can be more red and flared, and may occur anywhere. It may burn or itch. I know it’s hard, but try not to itch! But right now, as someone with chronic graft versus host disease, I can’t feel it, it isn’t painful, but it may make my skin less elastic, and does impede my joints a little bit. But I’m largely OK now!

     

    Usually, they’ll tell you to come into hospital as soon as possible if you get a fever or infection symptoms of any kind. With COVID-19 going on right now, clarify with your doctors if or when to come in. Many hospitals, including mine, will give you a card to get you into ED faster. Even after the pandemic ends (which may not be for years officially), it may be wise to wear a mask and avoid crowded areas too.

    Depending on your donor and your status, you may also get exposed to viruses that may put your graft (your transplanted cells) at risk. Your doctor will likely have you on prophylactic, preventative, antivirals, antibacterials, and maybe antivirals too to prevent this. And they’ll likely check your levels of various medicines, and monitor for these viruses too. This is why it’s really important to see your doctors and get your blood tests as much as they want you to. Hopefully, this will go from weekly appointments to fortnightly, to monthly, to 3 monthly, to yearly. And then comes long term monitoring.

     

    You also generally feel tired. I did after both transplants for months. Some of the medications you may be put on have annoying or frustrating side effects – eg. prednisone is a steroid medication (not the muscle building type unfortunately), which can make you angry, make it hard to sleep, and make you gain weight. But it’s also lifesaving. It’s important to keep in touch with your doctors to monitor this.

    The way cancer changed me used to really impact my mental health. To the point where, even though it was harmful for my health, I didn’t want to go out because of how it affected my looks. This is me years afterwards, but straight after chemo, on 100mg of prednisone, I had the classic “chipmunk face.” But I got over that after a while. This is how. I hope it helps those of you who may suffer from this out too. 

     

    After 3 months, you may also develop chronic graft versus host disease (cGVHD), which may manifest all over your body, and may get severe too. it’s important, once you get signs of anything weird, to tell your doctors about this so they can treat it, again. And treatment may last longer or be chronic, as the name implies. I still have some, 8 years out. But again, everyone’s different in this. I’ll make a post about this later – but there are many organs it can impact, from your skin, to eyes, to lungs and in rare cases, even heart. It’s important to get on top of this early. But the good news is, in many patients, it either ‘fizzles out’ or ‘plateuas.’ But without treatment, it can worsen, even after you’ve got it under control. So stay connected to your doctors and listen to their advice!

     

    That’s the transplant process, in summary. I know it’s a lot of information. But the main thing, is it a marathon. But it is also curative – it was one of the first curative options we had for any cancer. Though it can be dangerous, it has a good chance of fixing many diseases. Your doctors wouldn’t be doing this to you if they didn’t think it could help.

     

    I hope it makes sense. Let me know if you have any more questions. And sign up, do email me at info at nikhilautar dot (com) with any questions, and stay in touch!

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  • Bone Marrow Transplants. They Seem Scary…. But They’re Really Not. And They’ve Saved Me. Twice.

    2 years ago, to this day, I received a bone marrow transplant.

    It was the hardest thing I’ve gone through, as a cancer patient.

    I spent weeks stuck in a bed, subsisting on unsolid food, barely drinking and in intense pain – even with morphine!

    And for months after it, I was fed into a spin-cycle of maladies, starting with my skin feeling like it was burning for days on end without relief, followed by months of sickness and huge shifts in weight and ending with the a relapse and the knowledge that I’d have to go through it all again in my second transplant.

    But it saved my life.

    And I’m eternally grateful for it and for my donor.

    One thing that may astound you is the fact that the transplant took only thirty minutes, didn’t involve any pain – it was just a minor, drip-like infusion!

    Even DONATING bone marrow doesn’t mean having a needle put into your bones these days – at any point!

    Bone marrow transplants are the cure to variety of illnesses – not just blood cancers/disorders which I speak about mainly on this post.

    It has cured AIDs, which has only happened twice, EVER.

    And it’s the only way possible for a mammal to change blood types.

    Personally, I’ve had 3.

    Click here to skip to a particular section of this post:

    How it works

    Finding a Match

    How YOU can become a donor

    What happens to the donor

    What happens to the patient

    How It Works:

    So how does it work?

     

     

    Basically, a bone marrow transplant, also known as a haematopoietic stem cell transplant, replaces your old bone marrow with someone else’s. You can also use your own cells for this, but for this post, I’ll only talk about allogeneic transplants, ones you get from other people, rather than autologous ones which you get from yourself.

    Bone marrow is the soft, spongy tissue inside your bones which make your blood. It’s usually filled with haematopoietic stem cells – cells which rapidly divide over and over again and transform with the aid of certain hormones and chemical messengers produced by your body to eventually become your blood cells.

    When a disease process affects these stem cells, they cause a malfunction in your blood cells which has a wide range of complications as your blood is responsible for delivering oxygen and nutrients to your body, and also your immunity, amongst other functions. If that disease involves a change in the actual DNA sequence of the stem cells and divide so it begins to take over the normal stem cells (in other words, if the disease is a cancer) and chemotherapy is not an effective cure for it, then a stem cell transplant can become the best curative option.

    Now here, I wanna make it clear what I mean by “Bone marrow transplant” in this post. I’m referring specifically to Allogeneic bone marrow transplants – one received from SOMEONE ELSE. It’s possible to have an Autologous BMT too – in a procedure where your own blood stem cells are collected, so that they may be injected back into you after treatment. This is usually done to get very high doses, or treatments that would otherwise have killed off your vital bone marrow for good, into a patient, without killing them. The collected cells are stored and injected back into the patient after treatment has taken effect and remnants of the drugs have left the body.

    What an allogeneic stem cell transplant does is get someone else’s bone marrow, blood producing cells into you. Not only does that allow for, if required, the same high doses of chemotherapy and other treatments to be given, it also gets someone else’s white cells (white cells are blood cells, made in the bone marrow) into you – their immune system. And this had the added effect of them attacking your cancer cells, where your old immune system couldn’t (often, cancers have special mechanisms by which they can evade your immune system), or of getting a new immune system in there to replace the old one.

    The Procedure:

    An allogeneic transplant involves, on the patient end, first, some chemotherapy and radiation to the entire body (blood production, though often limited to bigger bones like your sternum or hip bone in adults, can occur in any bone in the body) to ablate, or kill off, your old, diseased stem cells. Less intense chemotherapy regimes can also be given, in diseases with lower agressiveness or in patients who can’t take as much of a battering (my second transplant, due to all the drugs and radiation I’d had previously, was done using a “reduced intensity chemotherapy” regime. Many older patients are now able to get bone marrow transplants where they weren’t before due to these regimes).

    The major side effect of this step is that your blood production halts, or stops outright, meaning you will be much more likely to bleed and bruise in that period and be very susceptible to infections – which are even more life threatening as you don’t have white cells to kill them off. Many of the drugs also have side effects of chemos (they often are chemos), and the radiation itself can cause severe mouth ulcers in some. This in itself makes the procedure very risky.

    After this is accomplished, you inject your donor’s stem cells into your body in order to replace it. The donor’s stem cells take around 3 weeks to engraft, or take residence and begin working, in your bone marrow and from then on your donor’s stem cells become your own. Which means that from now on, you’re producing YOUR DONOR’S blood cells instead of your own.

    The intent is not only for his (or your donor’s) cells to take over and start making proper blood cells again, but also to stop your old stem cells from coming back. You see, when his cells take over, his immune system does too. This is what is trying to be achieved in the whole procedure actually, a change in the immune system – as his immune system, being different to yours, will, hopefully, kill off any old stem cells of yours (including your cancerous ones) that remain. This is called the Graft Versus Disease effect (GVD).

    The problem is, there is also a good chance that his immune system will also find your body’s other organs to be foreign to it and it will attack them too. This is called Graft Versus Host Disease (GVHD). And it is a big reason why it’s seen as even riskier than even chemotherapy and radiation.

    In order to reduce the impacts of GVHD you are given some immunosuppresive drugs, which, as the name suggests, suppresses the immune system. When given early, it also prevents your old cells from coming back from the radiation and chemotherapy to cause rejection.

    Examples of these are methotrexate, and cyclophosphamide, given before transplants to reduce both the risk of acute GVHD and the chances of your immune system from rejecting the donor’s stem cells, cyclosporine in the long term to manage chronic GVHD (GVHD that presents 6 months to years after a transplant) and prednisone, a corticosteroid, to manage acute GVHD (GVHD that presents after engraftment. Prednisone can also be given long term to manage cGVHD, and many of these drugs are used at different points).

    GVHD can be life threatening, if not managed well. GVHD is a big reason why a transplant is seen as a very risky procedure. And though acute GVHD is more dangerous, chronic GVHD can have long impacts into the future.

    But it’s not all bad news. Actually, the presence of GVHD and having a more severe version of it is correlated to a higher cure rate because the GVD will also be stronger. It’s a balancing act. You don’t want too much severe GVHD but a little bit is good as it indicates a good level of GVD (graft versus disease) as well.

    And if you catch GVHD fast, and do as recommended by transplant hospitals, and rush to emergency, or call up your doctor immediately to initiate treatment in the critical periods (up to 3 months after a transplant, or when you feel classic symptoms of GVHD like fevers, gut pain/diarrhoea, skin prickling/redness/rashes or eye dryness. It can affect many other organs in different ways too) – it is often gotten on top of!

    Finding a match:

    When you’re being matched to your donor, it’s very preferable to have a complete HLA match. Basically your HLA is how your body recognises and differentiates your own cells from that of other foreign cells. You inherit your own ‘HLA settings’ from your parents, half from your mum and half from your dad and there are many HLA subtypes people can have, making it very unlikely for two random people to be matched to each-other.

    Usually there are 6 main subtypes they look at when they’re trying to find a donor to match for you (they can go to 8 or 10 or more as well – I was a perfect 10/10 match for HLA with my donor). You have a 1/4 chance of any sibling being a match for you. In fact, transplants from siblings get lower amounts of GVHD, so they’re seen as less risky (by the way – even being a 10/10 will result in GVD and GVHD occuring, as there will always be little differences between your donor’s immune system and your own). But outside of your immediate siblings, the chances are very low due to the sheer number of possible HLA subtypes combinations that there are. But they do happen.

    That’s where the bone marrow donor registries come in.

    How you can become a bone marrow donor:

    Bone marrow donor registries are usually done by country. It’s basically a huge database of people’s HLA combinations.

    The process of actually joining the registry varies from country to country but NOT ONE involves too much pain! NOT ONCE will you have to get a sample taken from your bone marrow! What they need is a tissue typing test – a test which checks which HLA subtypes you happen to have.

    In the United States, this involves simply buying a $5 test simply taking a swab of the inside of the your mouth and sending it away. In Australia, it involves a 20mL sample of blood, and has to be done while giving a blood donation (which takes less than 10 minutes and is no more painful than a blood test by the way) – and you have to ask and fill out a form in order to do it. This is done to ensure that everyone on the registry will be willing to actually give the donation. In the US a lot of people opt out of actually becoming a bone marrow donor in fear of the procedure, so finding a match doesn’t equate to finding a donor, which it usually does in countries using Australia’s approach.

    With the help of my doctors, I was extremely lucky to find 5 matches, from around the world, and have had 2 bone marrow transplant from them.

    Only 60% of people can find one.

    So we need you to join up on the registry. Especially if you’re from an Asian or Indian or Middle Eastern background. It is more preferable to find someone who’s similar to you – whether it be by race, gender or age, and these races in particular have critically lower rates of people joining the registry.

    Find out how, if you live in Australia, by clicking the link below:

    http://www.abmdr.org.au/dynamic_menus.php?id=1&menuid=2…1

    And if you live elsewhere, click here:

    http://bethematch.org/Home.aspx

    The procedure for the donor:

    The actual procedure rarely ever actually requires harvesting of actual bone marrow either (95% of the time it doesn’t and a good portion of the other 5% choose to go through the surgery process because they have access to general anesthetic through that pathway). The donor has to go through a series of subcutaneous injections, small injections under the skin – usually into the belly or arm, of a hormone which increases the activity of stem cells and causes them to enter the blood more. From there, blood is collected from the donor from one arm, siphoned through a machine which separates the stem cells from the regular blood, and the regular blood is injected back into the patient’s other arm.

    There is a chance that you’ll need to have surgery to remove actual bone marrow from your bones as well. Though it is unlikely nowadays, the procedure is done under general anesthetic meaning you won’t feel pain from the operation, and is very safe too.

    The procedure for the patient:

    The actual transplant is a bit of an anticlimax. The stem cells, collected in a bag, are infused into you, just like a saline drip, except with blood. In some cases, or in cases where a complete match wasn’t found, you can get a reaction to the actual cells.

    What is dangerous during the procedure is the chemotherapy and radiation which kills off your original stem cells.

    As with any systemic chemotherapy, your fast-growing cells are killed off. This includes not only your bone marrow, but also things like your hair and the lining of your gastro-intestinal tract. This leads to very low blood counts and hence tiredness, very low immunity and higher chances of bleeding, as well as abdominal pain and diarrhoea or constipation. There are a range of other side effects too such as nausea and taste changes which aren’t pleasant to say the least – but all of these can usually be controlled with medications.

    The low immunity in particular is of huge concern. Your neutrophils, the white blood cells at the front-line when fighting infections, plummet to 0 and not only do you become more susceptible to infections, you also become very weak at fighting them. In fact, it’s the leading cause of death in not only bone marrow transplants, but also in chemotherapies and even in hospitals. Hence it is important to stay away from other people who may have infections during a transplant, and also important for appropriate hygiene measures to be taken, such as always sanitising your hands before allowing others (including doctors and nurses) to touch you and being placed in a room where the air is always being filtered.

    Often, despite these measures, you can still get infections from your own body – it’s something you can’t help. These usually manifest as fevers or shakes or coughs and the like and are treated very aggressively, as your body has little to no capability of fighting them. Don’t worry though – medications can take the place of your immune system while it’s weakened – so infections are mostly controlled if caught early.

    The total body irradiation is another factor which comes with a range of side effects. The procedure itself is a little daunting at first, involving being beamed with radiation for 20 minutes whilst being placed in a box and held still by rice bags, but after a few times (it’s done once a day on a 5-7 day cycle), you get used to it.

    Again, it will cause your blood counts to drop and subsequently cause the cascade of side effects that come from that but it also causes skin irritation and in particular, mucusitis – or pain in your mouth and throat which, in my transplant, was the worse symptom. I found intense pain on swallowing – even if it was water or my own saliva and hence spent almost 3 weeks eating little more than less than a tub of gravy or custard and little sips of water. A morphine pump wouldn’t even help with the pain, and the sad thing is, 85% of patients who go through total body irradiation get this. But there’s a way around this too – a nasogastric tube which allows for food and water to be pumped into your body rather than forcing you to swallow it through a very sore throat.

    There are also other ways of doing transplants which don’t involve the radiation aspect of it – and my second transplant is an example of it. It was a transplant whose pre-conditioning only involved chemotherapy(and that too a less intense variety of it) protocol known as RIC (Reduced Intensity Chemotherapy).

    Bone marrow transplants are complicated, often risky procedures. They’re hard and often scary, and unfortunately necessary for some. But they give a second chance for people facing cancers, and other blood related or autoimmune diseases, at life.

    I can never be thankful enough to my 2 donors for what they’ve given me – a total stranger – to them. And they haven’t asked for anything back from me.

    They’re angels.

    I hope for a day where no-one has to go through the things I went through during my bone marrow transplant. ‘Til that day comes though, be sure to join your country’s bone marrow registry and become an angel yourself.

     

    To join the registry:

    USA

    www.bethematch.org

    Britain/UK: https://www.nhsbt.nhs.uk/british-bone-marrow-registry/how-can-i-help/

    Australia: www.abmdr.org.au

    Brazil: http://www2.inca.gov.br/wps/wcm/connect/orientacoes/site/home/informacoes_sobre_doacao_de_medula_ossea

    Canada: https://blood.ca/en/stem-cell/onematch-information-new-registrants

    India: http://mdrindia.org

    Those from other nations (though this is aimed at professionals, you can search for your nation, and find organisations that have and contribute to registries there):

    https://share.wmda.info/display/WMDAREG/Database;jsessionid=269E92F9EA24171227BF11FE71508EDA