Day 18, Chimeras

Posted by Becky

Today's topic is what's happening in Leif's bone marrow right now, and what that means for his future treatment.

The doctors say that the blood Leif has at the moment is being made by both his own and the donor's stem cells. Over the 100 days post-transplant, they will be checking Leif's level of chimerism, meaning the ratio of new to old cells in his bone marrow. The goal is for Leif to have more than 95% donor cells by Day 100. If he has 100% donor cells, he'll have complete chimerism. If he has some percentage of his own and some of the donor's he'll have mixed chimerism. If he has all his own cells, that's a graft failure and we hope that doesn't happen. The term "chimerism" comes from a Greek mythological creature with the wings of an eagle and the heads of a lion, a goat, and a dragon. In genetics, a chimera is an animal that has different DNA in some of its cells than in others. Some male tortoiseshell cats are chimeras, and so are stem cell transplant recipients.


We do not expect Leif to look like this, regardless of his level of chimerism.


Leif's stem cells were beaten up by the chemotherapy and radiation, and the donor cells weren't. That should give the donor cells an advantage, as they duke it out for territory inside Leif's bones.
The doctors can test for chimerism via blood test or bone marrow biopsy. Leif will be getting bone marrow biopsies, to check for both chimerism and lymphoma. As Leif describes it, although the cancerous B-lymphocytes have been cleared out of his body, the factories - his stem cells - are still there. We want those to be replaced by the donor's healthy stem cells. The doctors have a number of ways of adjusting his treatment, to achieve the goal of complete chimerism.

Leif's been sleeping a lot (about 18-20 hours per day) since he got home, which is expected. He's been waking up to take his pills, shower, go for his all-important daily walk, and eat. Today we went for a drive; I went to the office supply store, grocery store, and L.L. Bean, and Leif stayed in the car and looked at the great outdoors. He should not go out in public for quite some time yet, except for his necessary hospital visits. We got him some new warm gloves; the circulation in his hands isn't what it used to be, and his hands have been getting really cold on his walks.

He has more energy today than he had yesterday, and we hope that trend will continue. As his energy increases, I expect him to become stir-crazy. One of the problems with being immune suppressed is that you can't feel it, the way you can feel being sick. It's hard to believe you should not be out and about, increasing your exposure to pathogens, when you basically feel fine. So one of my jobs is to keep Leif reined in a little bit. Wish me luck!

Day 17, Napping and drugs from fungi

Posted by Becky

Discharge from the hospital involves a lot of discussions and information transfer, so Leif was awake most of the morning and early afternoon. Right around the time he was cleared to leave, he was overcome with the need to nap, so we left the hospital about 5:30 yesterday afternoon. After a couple of pharmacy stops and a run by the store for orange juice to take his ciclosporin in, Leif was able to get home and eat some freshly home-made food, rather than the food made a day or two before that I bring him in the hospital. Other than eating, he's been taking full advantage of this opportunity for uninterrupted sleep.

When he got home, he got to see the gorgeous quilt made for him by Rhonda's craft group. It arrived a day or two before he was discharged, and since they discourage bringing your own bedding into the HSCU, I saved it as a welcome-home present. Not only is it beautiful, it's very Leify, with fern fronds and artichokes in the fabric patterns. 



Leif feeling the love while napping. Quilt made by Rhonda and her craft group, afghan made by my mom, futon from the Danish Literary Society.



His medication schedule is pretty intense these days. Since he's had issues with ciclosporin and nausea, he takes his 15 other pills about an hour earlier and lets them digest before taking the ciclosporin. Figuring out which pills weren't digested yet after he throws them all up is a game we don't like to play.

It is not surprising that ciclosporin (also spelled cyclosporin and cyclosporine) tastes awful. Under normal circumstances, people should not eat the stuff. It's made by a fungus, Beauveria nivea, and suppresses T-lymphocyte activity. The story of its discovery and development is interesting. Leif is on a large dose right now, and as time goes by he will decrease the amount he takes, which will allow his new T-lymphocytes to become more active as they get used to his body. The more active they are, the better they will fight infection, replace his "fired" bone marrow, and fight lymphoma cells; but if they get too active too soon, they will attack his body. At every clinic visit, the doctors will check Leif's ciclosporin blood levels and adjust his dose if necessary, to make sure his levels are in the proper range for the current phase of treatment.  

Leif's other immune suppressant drug is mycophenolate; it's also derived from a fungus, Penicillium brevicompactum. Mycophenolate suppresses both T-lymphocyte and B-lymphocyte activity.

Day 16, Leaving the Hospital

Posted by Becky

Leif's blood counts have continued come up nicely; his neutrophils today are 1490. They expect that to drop somewhat Friday, since Leif did not get a Neupogen shot Thursday. His hemoglobin is holding steady at 7.6, and his platelets shot up from 32 to 50 between Wednesday and Thursday. He's still on track for discharge from the hospital on Friday (today, technically, since I am posting this after midnight Eastern time). He has not had any headaches for a couple of days, and they are gradually reducing his pain medication with no ill effects so far. On Thursday he switched to a liquid version of ciclosporin, the medication that was making him so nauseated, and he's able to get that down and keep it down. It tastes awful, but he can't smell it, which seems to help.

It's a little daunting to go from 24-hour medical monitoring to being on our own just like that. But we have a lot of information about what to watch for, what precautions to take, etc., and Leif will be seeing someone from the transplant team weekly for the next few months.

Leif doesn't have any more hospital stays planned. It is relatively common for transplant patients to need to be readmitted to the hospital to be treated for infections or GVHD; if he does need to be readmitted, it will be to the transplant unit here at DHMC. We'll be staying at our Vermont apartment for at least 84 more days (until 100 days post-transplant) to be nearby for the weekly clinic visits.

My parents, aunt, and landladies helped out with some housecleaning assistance, and the apartment is super clean and dust-free, to reduce Leif's chance of contracting any infections. He won't be able to go out in public for a while or have many visitors - I'm not sure for how long, but like nearly everything else, I'm guessing it depends. I'll keep everybody updated as his restrictions ease. At first, he'll probably be too tired to get up to many shenanigans anyway. He's been sleeping about 20 hours per day here in the hospital.

Day 13

Posted by Becky

The doctors are still trying to track down the source of Leif's headaches. Based on his symptoms, they are not very concerned that it might be something serious, like bleeding in his brain or a tumor. It could definitely be a confluence of factors - a vicious cycle of tight muscles causing pain causing his muscles to tighten; plus clogged sinuses, low blood counts and mild dehydration (they run transplant patients a bit dry on purpose), lingering pain from his jaw, etc. etc. He has the same nurse he had yesterday, who is committed to staying on top of the pain with whatever drugs are necessary, while everybody continues to try treatments that will get at the source of the problem. They are going to try giving him fluids and blood today. Even mild things like taking a hot shower to unclog his sinuses, and massaging his feet, which also unclogged his sinuses (!), can help ramp things down and get him out of this vicious loop. They just sent in a massage therapist who's working on him now.

His white blood counts are continuing to come up. His neutrophils are 230 today, and his platelets are basically holding steady. His blood counts are likely to bounce around as opposed to rising steadily, but things are looking good.

I asked the doctors how Leif's liver looks, and they were all smiles and said it is doing great - no sign of veno-occlusive disease, and he's unlikely to get it now. Regarding acute Graft-vs-Host Disease, they say it's early for any sign of that to show up now, but it's at equal risk to occur any time during the next 100 days. They're going to talk with the Infectious Disease team today about what antibiotics he should go home with. If his blood counts continue to recover the way they have been, Leif could be discharged as soon as this Friday, Day 16! That is sooner than we were expecting, but we won't complain.

Transplant Day 12

Posted by Becky

Leif is doing well in the grand scheme of things; no infections, and today his neutrophil count is above zero again for the first time in four days. His platelet count also is up, from 21 to 34, without any transfusions.

He is not feeling great, though. He is still fighting the headache that started last week. It hasn't gone up the pain scale to 10 out of 10 again, because he's figured out that a dose of IV Dilaudid when it starts ramping up will keep it from getting out of hand. But, he still has the jaw pain that started after the first headache. He hasn't tapered the painkillers down as much as he'd hoped to by now. It is possible that the painkillers themselves are contributing to the muscle tension that is clearly contributing to the headache. He has severe tension in his neck and shoulders; I'm doing what I can with backrubs, and he's using tennis balls, heat, and stretching to try to soften up those muscles as much as he can.

The doctors are going to order an MRI to check again for causes on the inside of his head. This kind of pain is not typical for transplant patients, so they are having a lot of discussion about what might be causing it and how to treat it. His nurse today is also pondering the question, and she put together a pain management strategy with Leif to try to get ahead of the pain, rather than chasing it. Headaches are hard to diagnose and treat if there's no obvious cause for them, and this will need to be under control before they can send Leif home.

He also has neuropathy (a burning sensation) in his lower legs and feet, some numbness on one side of his mouth (a known ciclosporin side effect), sore abdominal muscles from throwing up, pain in his bones and leg muscles, and his usual spleen pain. The only spot that doesn't hurt is his butt, which continues to hold its own against infection. Except for his head, none of this pain is very bad on its own, but cumulatively, it's giving him a rough time. He's been going for at least one walk a day regardless. Keeping active is one of the most important things he can do right now, along with continuing to eat well, so that's where he's putting his limited energy.

The criteria for sending Leif home are that his neutrophils need to be up into the target range, all his IV medications will need to be switched to pills and of course his pain needs to be under control. That could happen as soon as the end of this week! He's entering the time frame when he's at highest risk of veno-occlusive (liver) disease, and he'll be at risk of acute Graft-vs-Host Disease starting soon and for the next three months. The team will continue monitoring him closely for any symptoms until Day 100; but they don't need to keep him in the hospital to do so, although they might need to re-admit him if anything flares up. As the doctors have warned us, this is a marathon, not a sprint.

Leif is fortifying his spirits with good food (lentil stew, greens, pizza delivery), good books (Moss Farm by Van Reid, Sunlight and Shadow by Mark Helprin), and his new UFO-style remote-controlled quadcopter, which can do loop-de-loops.

Day 6

Ugh. Last night was rough. I had my first migraine, and a horrible spell of nausea leading to projectile vomiting. In fact, I think I sprained whatever muscle it is that makes you vomit, and I also popped by jaw. Even now, my jaw feels like I took a roundhouse kick to the head. 

I don't usually rate my pain a "10" when I am not passing out from it, but this was almost unbelievable. If this is the sort of pain that most people with migraines go through, I am impressed that they carry on. I am sincerely hoping that this was a random one-time thing for me. It was so bad that I could not see out of my left eye. So of course, they whisked me down for a CT scan, because headaches like this are usually caused by bleeding in the brain or a brain tumor. My CT scan came back negative, thankfully. I literally was half-blinded by pain, and nothing else. They gave me dilaudid, which eventually brought it down to an "8", which on hyperboleandahalf's pain scale is "I might actually be dying, please help."

This was a lot better, but still not great. After two more doses of dilaudid, it was down to a "3", which, while painful, I can tolerate. I was able to fall back asleep and slept until they took bloodwork at 4am. Other than being woken by the nurses and doctors every few hours, I have slept all day, and got up at about 3pm to take my walk and do my exercises. I still felt fragile and everything was hard, but it is really important to do every day, so I do it no matter how I feel.

I got back from my walk and fell asleep for about an hour, carefully ate some dinner, and am posting this before I go back to sleep. I can see out of my left eye again, but there are some weird after-images when I close my eyes. No one know what caused this and we all hope that is just random unconnected with my bone marrow transplant. 

It occurred to me that I had used a decongestant nasal spray that I have not used during this treatment, and perhaps it reacted with one of the drugs that I am currently on. I am sure not going to test this theory by trying it again. There is a limit even to my scientific curiosity. 

Other than last night, the transplant is going well. Dr. Meehan, the lead oncologist, pronounced my lymphoma gone, although he is always careful to say that it is still a long and dangerous road before I am actually healthy again. Infection, host-donor graft disease, liver or kidney failure, and relapse are the most likely difficulties ahead. So far my numbers look really good, and I have not had any problems with any of the treatment drugs. Good thing I was never a binge drinker, since my liver is under a lot of strain with all these drugs. I have to take about 35 pills a day plus about 8 drugs through my central line. I can't wait until my donor's stem cells move into my bone marrow, take over, and start pumping out white blood cells. Go donor cells! Go!!!

Leif

Day 2, waiting and watching

Posted by Becky

What happens now? Now we wait. Although Day 0 was a major milestone, it's not a big clinical event, in the sense that there's not going to be a lot for the doctors to do or learn immediately; real news about how the transplant went is still weeks and months away.

Leif's blood counts are expected to go down for at least three more days. They're looking decent at the moment, decreasing pretty slowly. The infusion of stem cells hiked his blood counts, since they're a blood product. As they go down, he'll again be at a high risk for infection. The good news is that his bottom looks better than it's looked since he got to DHMC. The surgeon and transplant specialist are both quite pleased at how it looks, and it's continued to heal noticeably over the past week. There is still a small area of hardness (induration is the technical term), indicating infected tissue (cellulitis), about the diameter of a nickel or dime. Just over a week ago it was much bigger, so he's come a long way. We'd love to see it completely gone before Leif's neutrophil count drops below 500. Go, little neutrophils, go!

During the time that his blood counts are low, Leif will be once again be at high risk for infection. The nurses are watching him closely for any signs of fever, etc.

At about Day 16-17, the doctors hope to see signs that the cells have engrafted, in other words, that the transplant "took." At that point, Leif's blood counts should start to come back, and in addition to monitoring for infection, they will monitor for signs of graft-vs-host disease (GVHD), veno-occlusive disease, and all the other stuff we've been warned about. They will manage symptoms and monitor his levels of immune suppressant drugs. They will also be monitoring for signs of lymphoma. If they see signs of evil B-cells, depending on the timing, there are a variety of things they can do, from backing further off the immune suppressants, to more chemotherapy, even another transplant. As I mentioned before, Leif's champion donor collected so many cells, there are enough stored in the freezer for an entire other transplant plus (if I understood the conversation correctly - I wasn't taking notes) infusions of filtered T-cells.

Because Leif got a mini-transplant, the plan is to taper down his immune suppressant drugs relatively quickly; the donor cells have a big job to do, and the doctors want to give them as much rein as possible without endangering Leif too much with side effects. However, he will remain on some level of immune suppressant drugs for 9-24 months. It all depends on how things go.

Stepping back from the big picture to the details of today, this was a better day than yesterday. Yesterday Leif still had a lot of nausea and headache, wasn't able to eat or drink much, and had increasingly bad pain in his muscles, then bones throughout the day and overnight. He didn't have fever-type chills and his temperature was fine, but he felt chilly and generally miserable. So the doctors did two things:

First, at his request, they switched one of his immune suppresants, ciclosporin, from a pill to an IV. Leif is pretty sure that was the culprit in making him nauseated. He will need to switch back to the pill form before he goes home, but getting enough food is important too. Switching to an IV and back will help provide information about whether the nausea was being caused by the ciclosporin or something else.

Second, they told Leif to be less aggressive in tapering down his pain medication. His morphine dose has been quite high since he had that bad pain in his bottom and those infected nodules during the last hospital visit. The doctors want to protect his liver as much as possible, so they recommended that he start tapering off the morphine. Since the infections were clearing up so nicely and he was feeling so good, Leif felt OK decreasing his dose by about 15 mg per day for the last 3 days. Although his "pain sites" continued to feel fine at that level of painkiller, the doctors think that his muscle/bone pain, chilliness, and possibly the nausea are withdrawal symptoms. So, they've gone back up to nearly his original dose, and will taper by 15 mg every three days. That helped - Leif was able to go for a good walk today, cleaned his plate at dinnertime, and seems to be pain and nausea free this evening. I say "seems to be" because he slept poorly last night since he felt so badly, and he's asleep at the moment.

We met with an oncology nutrition expert yesterday. She's personally a vegetarian, so she was able to come up with a lot of Leif-friendly guidance and recommendations.

We're in the path of Nor'easter Nemo, so I am planning to stay at the hospital until Sunday. I bought some groceries based on Leif's requests. One of the things I bought, Marmite, turns out to be on the Do Not Eat list, so I will  be returning it and reading the "little blue booklet" again. Oops. I can return the unopened package to the co-op, so no harm done.

Day 0

Today is Day 0, and it is pretty anticlimactic, which is what we like. I had total body irradiation this morning which made me a bit nauseated. I seem to be more sensitive to it than when I started. For those of you that are interested, the dose was 2 grays. I asked for metal sunglasses like they have in tanning booths to help protect my eyes, but they did not have any, and the doctor said that the low dose might cause cataracts in the future, but no serious eye damage. Still, who wants to speed up cataracts. 

I also have had a headache for most of the day. I don't think that this is from the radiation, but perhaps some allergies flaring up? Or not enough liquids? Hard to say. I asked for some aspirin, but it conflicts with one of my other drugs, so they gave me 15 mg of quick release morphine instead. I am not sure that morphine is doing much for me these days. I may have become acclimated to the dosages that I have been getting. It did not even get rid of my headache.

The stem cells themselves went without a hitch. Day 0 starts the counting for the 100 days. I do not have to be in the hospital for that time, but I have to be close by, because after I am released, I will have blood draws 2 or even 3 times a week. They test for donor-host disease, which means that either the donor's white blood cells, or my white blood cells have decided that the other one is the enemy and should be destroyed. I hope that does not happen. If it does occur, they can give me drugs to suppress the immune response, but that raises the chances of infections. The test is fairly sophisticated and can only be done here - neither Waldo County Hospital, nor Midcoast Hospital, nor any other hospital in Maine can do them. If all goes well, after the hundred days, I will only have to come in once a month, but I will probably drive down for that.

Now we wait for the donor stem cells to move into my bone marrow and begin producing blood cells. This is called grafting, and can take 4 to 6 weeks. It is a relatively dangerous time as far as infection risk, so I am being as careful as possible. The good news is that my own neutrophils have not dropped to 0 yet. They are at 570, with 3-5 thousand being normal, and below 500 being officially neutropenic. We will see what they are tomorrow. I am sure that I lost a lot during the radiation, and the chemo will continue to drop my count for another 5 days. 

Leif

Transplant Day 0

Posted by Becky

Leif got his total body radiation early this morning, but he cleverly managed to sneak in a short walk beforehand. I say he was clever, because the radiation made him feel nauseated; afterwards, all he wanted to do was nap. After previous radiation sessions, the nausea wore off after a short nap, but this time the nap didn't cut it, and he needed to take some anti-nausea pills as well, and didn't have an appetite for lunch.

One of the pre-medications they give prior to stem cell infusion is Benedryl, which makes Leif feel bad, so he didn't get a break from feeling cruddy before getting the cells. He's still feeling rather nauseated and headachey; the nurses are giving him some painkillers and more anti-nausea drugs. They got the cells started at around 2:25, right when Leif's mom called to wish him well - great timing, Rhonda!

Leif's anonymous donor continues to be awesome; they collected 14 million cells, and Leif only needs 5 million today. The remainder will be frozen in case he needs more in the future. The cells came from somewhere close enough that no preservative was necessary, which is nice; if people react to the transfusion, it is generally to the preservative and not the cells.

Day -1 Countdown to transplant.

Yesterday, I got my new ports which will accept the stem cells. My existing port is too small for the cells to go through. While stem cells are only about 8.2 microns* (+/- 1.1 microns), which is about the size of red blood cells, they stick to the side of the tubes and so they need a relatively larger tube.

The surgery to put in my ports went poorly though. I was told that I would be put under. When I got down to surgery, I was told that I would not be put under, but would be given pain meds and anti-anxiety meds such that I would not feel anything and would not really care. I was fine with this, since it is what they did when they put in my original port, and all I felt was a little bit of pressure. However, this time, it did not work. They tripled the dose, but to no effect. Luckily the area was locally numbed, so it did not hurt much, but I could definitely feel it, and was definitely stressed. I need to talk to someone about the fact that all they did was increase the dose of a medication that was not working.

Anyway, I survived, and in the scheme of things it is pretty minor. If that is the most pain that I go through before the end, I will be a lucky guy. The new port was pretty sore yesterday, but today it is much better. They also pulled my PICC line, which went into my arm, so everything goes through the new central line in my chest. I really have more holes in my chest than a person should.

Tomorrow is my stem cell transplant. Below is a chart on how the stem cells turn into all the other blood cells in the body. It is sort of amazing to me that I have to replace all my blood cells just to stop the cancerous B cells. The chemotherapy effects all the blood cells, and it is the red blood cells, the neutrophils, and the platelets that I keep track of when I talk about my numbers going up or down.

As a random factoid, NK in the NK cell stands for Natural Killer, because it is so good at wiping out infectious material. The T cells and the B cells are actually NKT cells and NKB cells, but the NK is dropped for ease.

It is too bad that there is no way to leave the lower types of cells alone and only target the upper types of cells. Eventually, I suppose they will have some way of doing that. I am lucky that I live in a time when they at least have stem cell treatment now, so that there is a chance of fighting off this disease. Just 10 years ago this was a much more dangerous disease.

As far as I can understand, my job now is to avoid getting an infection, and to avoid host-donor disease. Host-donor disease is when either the host or the donor cells reject the other. There are various medicines that help with that, but they lower your immune system and increase risk of infection. I think I am pretty laid back, so I hope that my cells are too, and have no problem with these foreign cells moving in and taking over the job of blood cell production. I am basically firing my bone marrow stem cells for incompetency and outsourcing to immigrants. Does this make me a bad person? :)

Day -4. Countdown to transplant.

Back in the hospital, room 121, phone number: (603) 650 - 2121. I am on day -4 of the stem cell transplant, so I am getting my first chemo pre-treatment. I will have 3 of those and then a day off. On day 0 I get Total Body Irradiation (TBI) of 2 grays, (for those of you that are interested in radiation doses), and in the afternoon I get my stem cells. I will talk more about the whole stem cell treatment in a later post.

So, today was move-in day. We did not have a room assigned until this morning, so we had breakfast, and I hooked up to my Vanco, and had the rest of my medications. 10 pills. It is ridiculous. After the Vanco (which drips into my PICC line) was done, I had a little nap and then got up and packed. It is a little funny because I was not that excited about leaving the hospital last week, and today I had a hard time not dragging my heels on going back. But packing is simple - a few clothes, a few books, my toothbrush and my computer cover 90% of everything that I bring.

I am in the Hematology Special Care Unit (HSCU, pronounced hiss-scue), This is in the same area of the hospital that I have been in previously, but it is all behind glass partitions and the air even more filtered, and is slightly pressurized. The large vents in my room mean that I can not fly my toy helicopter in here. The drafts are too much for it, and it gets sucked up to the intake vent on the ceiling, or gets caught in the whirling draft caused by the blower vents and slams into the wall. The best place to fly is up on the 5th floor in the east wing anyway, so it will just prompt me to take more walks.

Anyway, the HSCU nurses are segregated from the rest of the nurses. They have a lot more training. So I know all the other nurses on the floor, but none of the HSCU nurses yet. My doctor, the resident, said that he thinks the HSCU nurses are the nicest, which is hard to believe after the amazing kindness of the other nurses.

I spent about an hour re-arranging the furniture the way I like it, moving everything in the room around. I sort of expected some resistance from the nurse, but she just smiled about it, recognizing me as a professional patient, who is no longer intimidated by all the "hospital" stuff. The chemo was only 30 minutes. Barely anything at all compared to what I am used to. Hopefully my counts will not drop too much during this time and my bottom will continue to heal.

Leif