It’s been awhile since our last update — and it’s been eventful, so this is kind of a long one. 

Our warrior has been finishing up his semester, going to his high school football games, high school soccer games, eating Mongolian BBQ with friends, watching the World Cup with his BFF Alec and his family (Alec’s dad is from France), playing Mario Kart with us, playing Overwatch, and going out to dinner with Zack ❤️

We’ll get to those in a minute but wanted to update you on his treatment path.

Overall takeaway: the Total-17 Trial from St Jude’s that Sam’s been on has worked well to reduce his leukemia to a more manageable level, but it hasn’t reduced his leukemia to zero and we’ve reached a point of diminishing returns, so we’re moving to the next set of tools in the toolbox — we’re heading towards a stem cell transplant in March or April. 

We were hopeful that the trial would work, but for some reasons that we’ll share below, we weren’t sure that it would. And so while it’s disappointing, we’re at a place in his treatment that we kind of expected to get to. This is clearly a significant development in the journey to get Sam healthy, but lots of tools remain available to us, we’re in unbelievably smart & thoughtful & talented care (both at Stanford and networked across the country), Sam is robust and happy, and we’re optimistic.

And: we think it’s very likely that we’ll be able to get down to LA as a family for an annual event with lots of friends who are important to all of us! Some things to figure, and appears that we are more ambitious than most families are at this point, but we’re gonna get it.

Anyhow, here’s a little more detail: at present, the most sensitive tests for checking residual leukemia (called Minimal Residual Disease, or MRD) is a genetic sequencing technique called, creatively Next Generation Sequencing, or NGS) — it’s sensitive to 1 cell per million, while more traditional tests called flow cytometry had sensitivity of 1/10,000. While that sounds sensitive, it isn’t that sensitive, as humans have somewhere on the order of 25 trillion red blood cells, 147 million platelets, and 45 million lymphocytes. White blood cells only life for a couple of weeks, so you can do the math to figure out how many lymphocytes your body creates every second. It’s a lot!

The docs do this NGS test periodically by taking a marrow sample from Sam’s hip with a long needle — not a fun procedure, but necessary — and results take about 2 weeks to come back. When Sam was first admitted, his leukemia cells were something like 900k per million (not good!). A couple of weeks after starting chemo, that was down to ~5,000, and about 6 weeks later it was down to ~70 per million. So we were encouraged. After finishing the second phase of chemo, we got another biopsy, and got the results back a couple of weeks ago — they’re back around 4k per million. 

Now: this is still very, very low. He’s technically in remission by almost every definition, which rely on the older flow cytometry — and it’s on this resolution (1/10,000 rather than the 1/1M of NGS) that basically every protocol is based on. But Stanford and a few other institutions now are measuring at this finer resolution, and so while he’s clinically in remission, we know that his cancer has been increasing (again, in low numbers, but unmanaged, low numbers of cancer cells can turn into high numbers very, very fast).

This isn’t wholly surprising to us because Sam’s specific mutation is something called KMT2A rearrangement — for some unknown reason, some of the sequence of Sam’s chromosomes are swapped with each other. Really important: If you do a google search for this term, you’ll see lots of words like “dismal prognosis” that are scary — but if you start to dig in, you’ll see two things: (1) the populations of humans with this rearrangement are nearly all infants, and (2) the overall numbers are really, really small. That means that the articles and prognoses are not particularly useful really in any way — infants have a lot more things going on as their cells are incredibly plastic and fast growing. This mutation is also found in Acute Myeloid Leukemia (AML) and AML also presents more challenges to treatment in kids, than B cell ALL (Sam’s type of leukemia) does so don’t read KMT2A mutation in AML patients either. 

As near as we can figure, and we have been looking at this a lot, something like 5-10 teenagers in the US are diagnosed with Sam’s mutation per year. And that’s across all the health centers and protocols, so it’s very very difficult to figure out actual numbers and where they are. This rarity isn’t bad or good on its own — it just means that there is virtually no meaningful data on populations that get this, let alone strong, healthy kids like Sam. So we’re relying on the long experience of oncologists across the country to figure out the plan.

Because KMT2A is epigenetic (affecting the genes at a fundamental level), it has wide ranging effects on everything in your body, and tends to be more prone to relapse than some other forms of leukemia. 

Long story short: we now know that we need to take a new tactic to eradicate his leukemia. We’ve spent the last couple of weeks sorting out the best path — chemotherapy, immunotherapy, transplant, etc. And we’ve come to the conclusion that a stem cell transplant (sometimes called a bone marrow transplant) is the course of action that’s best to get Sam healthy.

We’re still learning about the process and implications, but at a high level, we’re spending the next couple of months working to get Sam into as close to zero NGS as possible (it should be very close) using something called Blinatumomab (nickname: “blina” (short i sound) and fun fact, the “mab” means monoclonal antibodies — a class of therapeutics that has been in the news a lot lately as a treatment for Covid — Kathy can actually explain the science!). 

Then around the beginning of March, we’ll go through a 10 day sequence of chemo and radiation to eradicate Sam’s current immune system, then he’ll receive stem cells that will create a new immune system from scratch (he’ll even have to get all his immunizations again! ) baput this time without the leukemia. He’ll be inpatient at LPCH for 4-6 weeks — so all of March and maybe part of April) — so they can do the eradication, transplant, and start building his immune system to a point where we can go home. His immune system will develop over the following year or so, getting stronger each month. We’ll test NGS at monthly intervals. And the plan is for Sam to attend his 2nd semester of senior year at Paly in person.

Phew. That’s a lot. We’re on a course now, focused on day to day. 

One thing I forgot to mention is that we’re in patient on the stem cell ward now, while we get the blina started — we’re hoping to get Sam home late on Christmas Eve, and looks like that schedule will hold, since he’s responding well so far. Then hoping that he & I can drive down to LA on Wednesday 12/28 (Kathy & Zack are flying down).

So that’s the story so far. We anticipate it’ll be a challenging few months, especially during the extended hospital stay. We’ll undoubtedly want to ask everyone for help throughout — I honestly can’t even express how grateful we are every day for all of you following along, calling, helping, thinking about Sam and us all — it’s been essential, and wonderful. 

But with a community of care and thoughtfulness and smarts like this, we feel very able to tackle the next phase in 2023 and get Sam healthy again. 2022 has been very challenging, but with some wonderful moments, too, and possible because of the friendship and support of all of you.

So: deep breath. Next play.