It is the 8^th night in the hospital. At least it is the 8^th night for Lochlan. I came home after dinner in order to put Torren to bed, then lift some heavy weights and play with Torren in the morning before heading back to the hospital. Torren has clearly missed me and was very sweet to me when I got home. It’s easy to get so caught up in grief, that you forget about the other beautiful things in your life. So I think it was good for both of us that I spent a night with her at home.

Lochlan started the day with a huge breakfast of sausage, scrambled eggs, pancakes, and a banana (dexamethasone is a hell of an appetite stimulant). Lochlan was hilariously eating the breakfast sausage and while moaning said “they made this really good.” Becca went home for a few hours to check out some garage sales with Torren and Locke and I went right back to sleep after breakfast. We woke up to discover that Bop and Grammy were in the room and Nanna showed up shortly after. Locke did not want to wake up. Locke was also back in depressed mode. There were presents for him, but he didn’t want to open any, he just wanted more band aids (his weird coping mechanism) and to sleep. During this time, the doctor came in and he was set up with his newest drug: L-asparaginase. This drug had to be given through his IV for 2.5 hours and he had to have heart and blood pressure monitoring throughout the administration, so this obviously didn’t help his mood.

 So what’s so special about this drug compared to the others? First, if you look at the last letters of a drug, it can give you some super basic information about the type of drug. If it ends in -ase, it is a protein that has an enzymatic function (enzymes DO things, like take one type of molecule and break off a piece of it or add something to it). Other common endings you might see in cancer: -ib, these are small molecule inhibitors of enzymes, most commonly kinases that are hyperactive in cancers (e.g., erlotinib an EGFR inhibitor); -mab, these are antibodies (e.g., Trastuzumab a HER2 inhibiting antibody);  So L-asparaginase is a protein that was originally discovered in bacteria (commonly produced from e.coli the main poop bacteria that always finds its way into lettuce) and is an enzyme that breaks down the amino acid asparagine to produce another amino acid aspartic acid. All human proteins are made from 20 standard amino acids in a particular combination, depending upon the sequence dictated by that protein’s gene. Usually a protein contains nearly all of the different types of amino acids. So if a particular amino acid is completely unavailable, then there’s going to be massive problems in synthesizing proteins, and cells are going to start dying. In human biology 9 of the 20 amino acids are considered “essential” which means our cells cannot make these amino acids from scratch and have to obtain them from our diet: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. The remaining 11 amino acids are considered “non-essential” because some or all of the cells within our body can make them from other molecules in our bodies: alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine, and tyrosine. So if L-asparaginase breaks down asparagine to aspartic acid, both of which are non-essential amino acids, couldn’t the leukemia cells just make more asparagine? That’s the catch. MOST cells in the body can convert aspartic acid back to asparagine. However, because blood cells (including leukemias) are used to being exposed to high levels of asparagine in the blood stream from our diet, they do not need to express the enzyme necessary to make asparagine. So L-asparaginase is really effective at starving leukemia cells of asparagine, while the vast majority of cells throughout the rest of the body could care less because they’ll just continue making their own. This drug has a special modification to it that greatly extends the amount of time it stays in circulation (weeks) so it doesn’t need to be given frequently and can continue to starve the cancer cells until they die a miserable death. However, the biggest risk with this drug is that our immune systems are keen on detecting and building a resistance to foreign proteins. So there is always the chance that Locke’s body will begin to recognize the enzyme as foreign and produce antibodies to destroy it. So it is currently only scheduled to be given once.

Becca and Torren showed up around when the L-asparaginase was finished being given. Upon seeing his sister again, Lochlan went from depressed and wanting to sleep, to smiling, chatting, and opening presents. It was like a totally different kid. After she went back home with Grammy, he became a bit more lethargic and cuddlier, but he smiled and made a few jokes and seemed so much happier. I need to get this kid home to his sister. We still don’t have a return date, but it will be after Monday. He’s getting hit HARD on Monday (vincristine, daunorubicin, methotrexate, and dexamethasone) so I think they want to monitor him for a few days for blood transfusions, etc. So hopefully we have a week or less left in the hospital. For good news, his neutrophils were at 500! Neutrophils and platelets have been steadily climbing despite the chemo (although I expect everything to plummet next Tuesday/Wednesday). Total WBCs are realllllly low as expected and a couple days ago his circulating leukemia cells were around 2%. So getting super low.

Well it’s super late, I need to go to bed in my own bed (which is now our cats’ bed). Once again, thank you everyone for everything. Everything is helpful, even simple kind words of support. Our friends from Indianapolis also designed and have put together a special Lochlan T-shirt drive. The shirts are super awesome, I can’t wait to get mine. There’s a picture in this update. The website is here: https://www.customink.com/fundraising/lochlan-the-lion-hearted. Keep the lion themed items coming! The lion is his spirit animal! Lion-hearted is his Viking name!

Love

Kevin and Rebecca

It is the 7^th night in the hospital. It’s hard to believe that tomorrow marks a week from when we checked into the hospital. The crazy thing is that I’ve been in a hospital for a whole week and I still have a cough. That’s my attempt at a joke following the devastating post I made yesterday. I thought it was funny when I told it to Becca, but I think there’s a good chance it isn’t carrying a lot of comedic weight in this medium. But seriously, the germs that the kids picked up that started this whole fiasco were crazy potent. And the air in this hospital is so dry. Because we came in with germs, we’re not allowed to get our own water or leave this room much (Locke isn’t allowed to leave except for medical procedures) because we are considered a threat to the safety of the other kids. I totally get it, but it’s just another layer of suckiness to this experience. They told us we won’t ever be cleared to walk around the hall.

Nothing really new to report regarding Lochlan’s diagnosis/prognosis. I’d say that the day was not as terrible as most of the other days. Lochlan was still sad and wanted to leave, but there were no breakdowns. Lochlan was still resistant to taking his oral medications, but no worse than normal and sometimes slightly better. Lochlan was super tired because the drugs are wiping him out so he was very cuddly all day. He had to get a blood transfusion because his hemoglobin levels dropped today (hemoglobin is the molecule that transports oxygen from your lung to the rest of your body and transports carbon dioxide from your body to your lungs so you can exhale and increase global warming. Sorry I don’t mean to make light of climate change, but cynical humor helps me cope. But seriously, if we could get all politicians to stop yammering about nothing all the time, might we make some improvements to the climate? Food for thought…)

I think I mentioned previously that Lochlan has been wanting to go to Grammy’s house so that he can play with the light up cars that she has (Magic track). The hospital actually had some magic track, which kept Lochlan entertained yesterday, but he was upset because they didn’t actually have the light up cars. Well mom pulled through today and got him his own set. We set it up to go under and around his bed and I set up all of his other toys as race spectators. I’d say he had legitimate fun for at least an hour. That was a win.

Also realizing that we have ourselves been on bed rest for the past week, Becca and I took some time to get some exercise. It felt good to just drown myself in some Wardruna and sweat for 30-40 minutes. I think we will do a better job of self-care over the next week.

Thank you all again for the love, support, care packages, food, and just everything. It has been so much help in so many ways. Lochlan has loved all of his presents. Tomorrow we get our first meal from the food train, so I’m pretty excited for that. Lochlan starts a new drug tomorrow (L-asparaginase) which carries a low risk of allergic response. I’ll go more into what this drug is for and what it does tomorrow. For now I need to assemble my luxurious couch bed and then meditate. Thank you again and we love you.

Kevin and Rebecca

This is the 6^th night in the hospital. Let’s start with the good stuff. Lochlan slept until 8:30 am! AND he wasn’t snoring, so that congestion seems to be completely gone. Great job antibiotics. He will, however, be staying on antibiotics for the foreseeable future because he has almost no functional immune system. I wonder if they can give a healthy fecal transplant once he’s healthy. Probably not, but someone must be doing research related to that. Also good news is that Lochlan’s platelets and neutrophils have been climbing since we started chemotherapy on Monday. For reference Lochlan had ~65,000 platelets per cubic millimeter before starting chemo (healthy is > 150,000) and is now at 115,000 per cubic millimeter. For neutrophils (the cells essential for fighting bacterial infections, which are some of the most lethal infections to the immune compromised patient) Lochlan had 0 per cubic millimeter for the first four days we were here. That count was up to 30 yesterday and 100 today. Healthy is >1,000 per cubic millimeter, so we’re not even remotely close. The reason why his platelets and various immune cells are so low is because the cancerous cells have essentially taken up the entire bone marrow and the bone marrow is where the immune cells originate. So once the cancer cells are being killed, there’s more space for the normal cells to grow. Our doctor described chemotherapy as sort of being like Round-Up, cancer cells are the weeds, and normal bone marrow cells are the flowers or grass. So seeing these numbers start to climb right away suggests that there were still some normal cells still in the bone marrow that had a little breathing room to begin functioning a little more properly. They also did a CBC and the immature cells are no longer detectable in his circulation. Which is also a good sign that things are heading in the right direction.

Also good news is that Lochlan went another day without having a fever and he ate really well for breakfast and dinner. That had to feel good. He was however still really tired and clearly depressed for most of the day. But he was really wanting to play with these particular cars that he usually plays with at Grammy’s house and the HDCH had them! Well at least had the right track, they didn’t have the light up cars like Grammy has. BUT it did get him out of bed and distracted enough to play with a child life helper while mom and dad went to get coffee and walk around to discuss what the plan was for the next few days. We both have spent most of the past 5 days in bed or in a chair and need to start thinking about getting exercise to boost our spirits.

Lochlan and I also got to have a dudes’ day for the second half of the day/night. Many of you are familiar with these events from when Lochlan was an infant and we got to spend a whole day together every week. This usually involved me spoiling him and taking pictures of it and posting it on FB. We haven’t had many of them since I obtained my PhD because Becca was staying at home with our now two kids. So it was good to hang out, watch a movie, play video games, and eat pizza (well he ate pizza, I ate sandwich meat and a luna bar since I can’t eat dairy).

Today was also the first real day that I ventured out of Lochlan’s room on my own. I went to pick up a stuffed lion that a friend of mine (Erin Williams) got for Lochlan. I met her at work (which is across the street and connected by bridges), which also meant that I ran into several of you. I realized I wasn’t handling this as well as I had hoped once I started talking about what was going on…

So what’s going on… we got the cytogenetics back today… So what cytogenetics is, is an analysis of the gross chromosomal abnormalities in the cancer cells. It’s used to tell if there are too many or too few of particular chromosomes (you should have two and only two of every chromosome other than the X and Y chromosomes where males should have 1 X and 1 Y and females should have 2 X) and whether any of the chromosomes broke and maybe fused to other chromosomes. While most cancers are known to gain or lose whole chromosomes or selectively delete or gain certain chromosome sections, leukemias frequently have chromosomes that break and then are fused to other chromosomes in a process known as translocation. Like Frankenstein, but less cool and more scary. The following is super generalized: The loss or gain of particular parts of chromosomes in tumor cells will give them a proliferative advantage due to loss of genes that inhibit proliferation or the gain of additional copies of genes that promote proliferation. The mixing and matching of chromosome sections in translocation events, however, often lead to different genes being fused together into something new, with a major effect being large changes in gene expression that support increased proliferation and/or prevent cell death. While the translocation events are likely random, the fusions that frequently result in a particular type of leukemia tend to be recurrent (only translocations that provide a growth advantage and lead to leukemia are going to be observed and documented). This means that many patients with leukemias will have similar translocations between different chromosomes. This information can then be combined with information regarding how well a patient with a given translocation responds to therapy and survives. So some translocations carry good prognoses for example: t(12;21). But some translocations carry not-so-good prognoses, for example: t(4;11)… Lochlan has t(4;11)… So Lochlan has a leukemia that is driven by a translocation that makes it more difficult to cure.

So this is shitty news. However, I don’t have a number about how shitty. Science is great at population stuff, but provides very little information for a given individual. What’s even more difficult calculation wise, is that this translocation is fairly rare for someone his age (something like 2% of ALLs for kids between 1 and 10). So there’s not a TON of information regarding prognosis in his age group. It’s common in infants with ALL (~50%) where it confers a poor prognosis, it’s uncommon in adults (~10%) where it also confers a poor prognosis. But in these populations, it usually presents with other bad features like high white blood cell counts and spine involvement, which Lochlan doesn’t have.

So the current plan is to hit this fucker as hard as we can up front. The doctors are doubling Lochlan’s dosage of dexamethasone and adding daunorubicin, a topoisomerase II inhibitor. Topoisomerases cause breaks in DNA in order to relieve tension in the DNA during replication. Daunorubicin binds DNA, then allows topoisomerase II to break the DNA, but prevents the repair of the DNA. The cell will sense major DNA damage and trigger cell death. The goal is to go into complete remission within the month.

However, this also means extra side effects. We can now expect significant reductions in his normal white blood cells as well as hair loss. If Lochlan survives this, he will also have to be monitored for the rest of his life for signs of heart damage, as this can be a late presenting side effect of daunorubicin. It also means that we will be staying in the hospital past next week Monday as had been originally planned. This sucks. We’ll get through it one day at a time, but it’s significantly more difficult emotionally and scary now.