We just got back the results from the NGS genomic test for Sam, and for the first time since June, there’s no detectable leukemia in Sam’s body. It’s a great milestone, and an important one as we head towards a stem cell transplant in March. But miles to go. 
We’re really, really happy about it, of course, but also trying to manage our psychologies — that word “detectable” is a tricky one, and leukemia is very very sneaky. 
As you’ll recall from previous posts, NGS has a resolution of about 1 part per million; and we’ve got something like 150M white blood cells in our body (and 300B overall, mostly red cells). When Sam and Kathy went to the ER in June, his NGS showed 900k leukemic cells per million (!); after a couple of weeks of chemo, around 7k, then after another month of induction, it was about 70 cells per million. After 8 weeks of consolidation treatment on high dose methotrexate it was back up to 4.5k, which caused us to head down the path of blinatumomab as a way to try to get Sam to as close to zero on the NGS before a transplant. That’s the #1 factor that correlates with a durable cancer-free future after transplant.
So it’s extremely encouraging that we’re at zero! The blina has been sort of miraculous and there appear to be very few side effects. Sam’s feeling really good, his hair’s growing back, and it’s generally been very manageable in ways that the chemo definitely was not. 
(The one thing that you do watch for on targeted therapies like blina and CAR-T is something called lineage switch, where the nature of the leukemia turns from ALL to AML, but that doesn’t appear to be happening for Sam at this point.)
In retrospect, because of the specific nature of Sam’s mutation (KMT2A-r), it feels like this blina-to-transplant path was always the one we would get to, as it combines the targeted nature of blina with the thorough eradication nature of a transplant. And in fact as Kathy has been looking and looking for the kids & teens with KMT2A-r ALL (there are very few — maybe 5-10/year in the states, but we’re really not sure, and they’re difficult to find), we’re starting to find families who have had similar experiences. We are also becoming amateur research oncologists — reading as many papers as we can find, at least (which has honestly been rough on my Facebook and Instagram ads — they are really, really trying to sell me medical scrubs in a variety of new colors — just about the only ads I see anymore) — and Kathy’s found some new papers from a group in Poland that suggests that KMT2A is resistant to methotrexate and maybe 6-MP (which is another of the core chemotherapies that Sam’s been on). 
This is one of our emergent learnings — we (humans) are very clearly on the precipice of some massive, foundational changes in how we treat disease. Sometimes called precision medicine, sometimes called individualized medicine. But in so many ways it’s clear we’re moving from mass population symptom & protocol-based treatments towards understanding more fundamental mechanisms of action that mean medical care may well vary from person to person even if they’re showing the same overall symptoms. In our case, it now seems pretty clear that because of KMT2A instead of doing methotrexate for the consolidation phase, we should have just gone to blina.
There are reasons we didn’t — Sam’s initial response to the St Judes TOTAL-17 standard protocol for ALL was really encouraging, and so we stayed on it.
We aren’t overly worked up about this — it was a reasonable path to go down. And we think we’re in a very good place right now that was sort of inevitable. We do wish we could have spared Sam the time in the hospital and on the HDMX — they were rough weeks. But hard to know, really.
What’s (maybe academically)  interesting is that there are starting to be specific mutations that are in the ALL protocol but treated differently — most notably something called the Philadelphia chromosome translation. Because it’s found in a reasonably large (maybe 30%?) portion of adolescents with leukemia and is also resistant to chemo (in some analogous ways to KMT2A-r) is, the treatment diverges from the standard protocol. It seems pretty clear now that as we learn more about KMT2A and other mutations that we’ll have more specific pathways for each. 
But we’re still in a somewhat awkward transition phase between traditional medicine and this new individualized approach. Which means that most physicians weren’t trained in school on it and are learning on the cutting edge. 
This is mostly really great! As I said: a miracle. But also requires a lot of reading & listening & checking & double checking & etc etc. I’m beyond grateful that Kathy & I are both (kind of) equipped to read & ask questions of some of the world’s experts on this stuff. And we know that once we get our own patient #1 healthy again, we’ll be spending a lot of time on helping get the field moved forward so that other families don’t have to be MIT & Stanford trained & connected to navigate the best path for themselves. 
So we’re making progress, and very optimistic! Given the positive news, this is probably a more measured post than you might expect, so just a note on that: Kathy & I are trying hard to manage our emotions & psychologies in a pretty narrow band around neutral — trying to avoid getting ourselves too up or too down on any given development. Because as good as any result is, there will be reversals and complications. And we know that the transplant is going to be rough sledding during the 4-6 weeks in the hospital and the 9-12 months rebuilding Sam’s immune system — no matter what.
And we also know that Sam is a very even-keeled kind of human. He does best when he just puts his head down and works through it all. He’s more interested, honestly, in the day-to-day of being 17, gaming & Snapchat & discord, figuring out school, and who he wants to be. Thank god for that, and it helps us all too — we note the medical progress, but mostly we talk about the non-medical side of life, and we’d ask that of all of you when you interact with Sam, too. 
Phew! That’s a lot more than I meant to write. We’re really happy & hopeful, and today Sam will get home with his 2nd bag of blina for the next 26 days, and we’ll figure out a lot about transplant between now & then. 
So here’s to blina & here’s to Sam. Next steps.