Day +38: Why we're still here

We are halfway through our eighth week at Children's, and more than six weeks post-transplant. In many respects Sam is doing very well. All evidence so far points to a successful transplant (good engraftment), and the HLH bio-markers the docs watch in Sam's blood are in a good place; no worries there. Though it's still relatively early, there are no signs of graft-versus-host disease.

Sam is feeling really good, too. He's alert and happy a lot, he's had only a single (and very brief) low-grade fever in the last 10 days*, and he seems not to have any discomfort. His blood pressures have come down a lot, which means he needs fewer meds (always a good thing), and he's being weaned off of steroids--also good news.

Alyson's first full day with Sam since she started work again this week. Sam was in fine form.

So the big picture looks good.

And yet we are still here, and will be until they can figure out why Sam's breathing rate is sometimes high and a bit labored. He is on oxygen, as he has been for more than a month, and has for 10 days or so been getting treated with nebulized albuterol. The albuterol helps control the symptoms but doesn't address the not-yet-identified source of the problem.

The number in white is Sam's respiration rate, which should be in the 30s or 40s. All the other vitals (green = heart rate; blue = blood oxygenation; pink = blood pressure) are good or very good.

Sam sounds clear in the stethoscope--has for weeks--and none of the testing they've done (multiple x-rays, CT scan, echocardiogram) has provided any clues. But the symptoms persist. The conventional wisdom is that he's still too weak to fight off the rhinovirus (common cold) he tested positive for on Day +1. Another theory: Sam's lungs were damaged by HLH back in June, and he hasn't yet recovered.

Sam gets a breathing treatment (albuterol) 4x/day.

Neither theory is very testable, so until they decide that this is actually a problem (and resort to more extreme diagnostic measures, such as a bronchoscopy), there's not much to do but try to treat the symptoms and wait for Sam to get stronger.

And that means not getting to go home.

* For a while he was crossing the (admittedly low) fever threshold of 99.5 °F / 37.5 °C every 24-48 hrs. That he's so much less prone to having a fever says good things about his recovery and lack of infection. It also bodes well for our discharge, whenever that day comes: the fewer times Sam crosses that fever threshold, the fewer times we'll have to bring Sam to the ER.

Day +29: A corner turned?

Lots of good things happening with Sam these days. First and foremost, they did a second, different test of the spinal fluid the took from Sam 10 days ago and found absolutely no evidence of inflammation. This, in addition to other factors, means that the docs are no longer worried that HLH is on the rebound--a huge relief for us. (One immediate implication: they've started to wean him from the steroids.)

I don't think Sam has had a fever in three or four days--that's the longest he's gone in weeks. His fevers have nearly always been brief and low-grade, but every time he goes above 99.5, they draw blood (to test for infection) and put him on a course of antibiotics. Fewer fevers means fewer meds and fewer reasons for nurses to take Sam's blood (which eventually forces him to get transfused).

Sam's oxygen saturation is better, his respiration isn't as elevated as it had been, and the congestion he's been fighting for weeks seems to have lifted. Maybe he's over the cold? He's also not holding on to fluids so much, perhaps in part because he's not getting so much fluid intravenously anymore (several of his meds are now administered orally). And he's not as hypertensive, which means he needs fewer BP-related meds.

Best of all, Sam is simply feeling better. A week ago, when we were still wondering if the HLH was back, one of our doctors told us that Sam's demeanor would be as important to their diagnosis as any lab result. In that respect, Sam has been killing it lately--he's been alert, social, and happy. The last five days have been his best in at least three weeks.

The docs will likely want another spinal tap in a week or two--unlike the body, whose state can be readily monitored through blood testing and other procedures, there are many fewer techniques for assessing the health of the central nervous system; extracting spinal fluid is one of them--but this was always part of the post-transplant protocol, not evidence of anything amiss with Sam.

More evidence that things are looking good: we are being trained on how to change Sam's dressing so that we can do it at home. Nothing's in ink yet, but if Sam continues on the current trajectory, I'll be surprised if we're not discharged before Halloween.

Day +25: Still reading tea leaves

Last week's tests of Sam's spinal fluid and bone marrow were not positive for HLH. That is, they showed no direct evidence of hemophagocytosis, the process whereby Sam's white blood cells attack his own body. This is good news, of course, but it doesn't seem to have been enough to convince our doctors that HLH isn't still sniffing around.

This view of Sam's bone marrow from June shows hemophagocytosis in action. The large, Pac Man-like white cell is devouring cells that it's supposed to leave alone. This was proof-positive of HLH back in June. Last week's bone marrow biopsy didn't show this, but as Carl Sagan apparently said, "Absence of evidence is not evidence of absence."

Many of the other bio-markers the doctors look at for evidence of inflammation are also inconclusive. They could be evidence of something else--if not something benign, then at least something expected given Sam's post-transplant condition, side-effects of the meds he's on, etc. So, with every symptom, lab, or test result the winds seem to shift a little bit. Right now it seems like the doctors don't feel they have enough evidence to begin an all-out assault on the HLH (that might not really be there), but they have put Sam back on a pretty high dose of steroids (dexamethasone) in order to subdue any inflamed white cells that might be HLH.

We are not happy about this--the steroids weaken Sam's bones, contribute to hypertension, and probably impede Sam's ability to fight his cold--but I suppose it's better than a positive identification of HLH. If we do see definitive evidence of the disease, then we face a Sophie's Choice of sorts. We can treat with steroids and more chemo, which would effectively undo the transplant we just went through (because the brand new immune system we just gave Sam would be damaged, if not completely wiped out, by the chemo), and that would require him to endure some or all of this process all over again. Which, in turn, would subject him to more meds and their side-effects, make him vulnerable to infection, etc.

Or, we can bide our time and hope that Sam's immune system grows quickly enough on its own that it can knock out the disease, whatever there is of it, before it starts trying to eat him alive again. And that is a race that Sam might not win.

Needless to say, we're hoping that the soft evidence is not, in fact, disease-related and will fade as Sam gets stronger.  In the meantime, however, we're watching Sam very closely and crossing our fingers that the reason we don't see stronger evidence of HLH is because it isn't there.

The continued uncertainty is nerve-wracking, but there are some good signs. First and foremost, the transplant itself appears to be very much on track. The donor cells are very well engrafted and Sam's blood counts are coming up faster than expected. His white cell count continues to rise, as does his platelet count. This is exactly what we want and need to happen.

Sam has stopped vomiting, and the quick but sometimes extreme bouts of discomfort he was having last week have disappeared. We're not sure what was going on in either case, but it's nice that he's more comfortable than he'd been, and great to have his awake and alert time filled with curiosity and smiles rather than cries of pain.

Finally, from the "good-news-if-dodging-a-very-big-bullet-is-still-considered-good-news file"...

Last week one of the overnight nurses saw what she thought might be seizure-like activity when she noticed Sam's arm extended and trembling rhythmically. Seizures are a possible HLH symptom, so the docs ordered an EEG with video so they could monitor Sam's brain waves. Sam's head was wired up so that he looked like some sort of electric Einstein (or Medusa?), then watched for 12 hours overnight. The video showed three occasions where Sam's arm did the trembly thing, but there was nothing in his brain activity to suggest that it was abnormal. This was an enormous relief for obvious (and some not-so-obvious) reasons. Suffice it to say that we had a pretty shitty 24 hours waiting for those results to come back.

Now if we can just get Sam to kick his cold, we might actually be able to take him home.

Sam is a boy...

...who adores his mom.

Day +18: An HLH comeback?

Sam's recent labs indicate that there may be some HLH activity in his body. The signals are mixed, however.

On the less promising side, Sam's ferritin and soluble IL-2 levels are elevated--not abnormally high, but higher than expected given his condition. Both are bio-markers for HLH, so both are red flags. In addition, Sam's triglycerides are abnormally high. This, too, is indicative of some kind of inflammation, including--although not necessarily--HLH.

On the other hand, the docs say HLH activity this soon after transplant would be unusual. Moreover, Sam's platelet count is healthy and rising. HLH attacks platelets, so a healthy platelet level would be inconsistent with HLH activity. Sam also recently tested positive for a (readily treatable) bacterial infection, and the associated inflammation could account for at least part of the ferritin and soluble IL-2 values, if not the triglycerides.

In short, we have mixed signals and need more data. Tomorrow Sam is scheduled to get another spinal tap (to see if there's evidence of HLH in his central nervous system) and his second bone marrow biopsy. Results, which we hope to see late Monday or early Tuesday, will tell us a lot more about what's going on.

It's ironic to be rooting for a bacterial infection, but I guess that's where we are.

We still have not yet seen results from the first chimerism (aka engraftment analysis) test, so we don't yet know how much of Sam's blood is his own and how much comes from the donor. Doctors are confident, however, that we will see continued evidence of good engraftment. Sam's donor was perfectly matched, and his blood counts would not be rebounding so quickly if the engraftment wasn't going according to plan.

In the meantime, here's Alyson and Rufus serenading Sam. Background melody provided by the mobile overlooking Sam's bed. Security courtesy of Mr. Shark.

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Day +15: An unforgettable day

Our room is in the Blood and Marrow Transplant section of a floor dedicated to Hematology & Oncology patients. The BMT unit's 10 or so rooms are behind two sets of magnetized double doors, and visitation is restricted because BMT patients are, by definition, in a fragile state due to their deeply impaired immune systems. Their admissions last weeks or months at a time, and they're here because they have serious, life-threatening conditions that require serious, life-threatening measures. Any way you slice it, it's pretty sobering stuff.

Patients are confined to their rooms except for procedures that have to be done elsewhere (surgery, MRI, CT scan, etc.), so the only people we see around the unit are staff and people that I presume are patients' family. We've never actually met anybody*, however, so we know nothing of the other patients except that they have recently undergone or are about to undergo a transplant procedure intended to cure/relieve/address some kind of blood- or cancer-related condition. We acknowledge one another in the halls, but only briefly and in an obligatory sort of way that suggests courtesy and empathy if not genuine interest. Anything more than that is more than we have the energy to muster. I've got my own horror show to watch. I don't need to know anything about yours. 

It has not been unusual for us to hear crying or screaming through the walls, but since we've never seen any of the other patients, we can't visualize who's making the sounds, or why. (In one case, we learned that the patient had an ostomy that required regular and, apparently, extremely painful attention.)

A couple of days ago we heard noises (cries? shrieks? wails? I haven't found the right word) that were unusually anguished and emotional, and occasionally punctuated by the sounds of impact--a body against a wall? fists on a table? After a few moments I realized that the sounds were coming not from the patient (a little girl, I think, based on the voice we've heard before), but from someone else--someone who soon began to scream "Oh my god. Oh my god." 

Within a few seconds, staff were flying down the halls from every direction into their room. Something was going--or had already gone--horribly, horribly wrong. We--Alyson, me, Alyson's mom, our social worker--traded alarmed glances but didn't speak. The nurse seemed to try to carry on as usual, but it was impossible to ignore the anguish and the commotion 10 feet away even though we could see nothing but flashes of humanity rushing past our door.

When I realized that Alyson and I were both starting to tremble and wither emotionally from the sounds--sounds that I imagined were coming from the mother of a child who was either dead or dying in front of her mother's eyes--I grabbed her and fled down the hall. We eventually made our way to a quiet exam room and closed the door until we received word that it was safe to return. There we sat in a long, quiet embrace, trying very hard to stop hearing that voice, and to stop imagining what might have been happening.

It sounds--and certainly felt--selfish to think about our own well-being when it was abundantly clear that our neighbor was actually experiencing something horrible; we simply wanted not to observe the horror. But under the circumstances, where we spend all day every day trying not to obsess over the possible significance of every vital sign, symptom, and test result, it was hard not to wonder if whatever was happening next door could also happen to us. Could Sam's condition turn south in a single moment like that? And if it did, how we'd react. Is that what I will sound like if Sam dies?**

We have since learned that the patient had a seizure--presumably unexpectedly--but is fine. She has been moved to the ICU, her old room now occupied by another patient. We've recovered from the shock and alarm, though we won't soon forget it. There's no question that the mother won't either.

Sam slept through it.

* You might expect people to want to bond with one another, to commiserate and empathize. After all, we spend hours, days, and weeks here enduring very similar kinds of hell. The hospital does arrange social gatherings for families, presumably for that very purpose (Sunday night pizza in the Ronald McDonald Family Room), but we've never attended. And if our own observations are worth anything, not many parents do.

** I no longer spend much time wondering if Sam will die. I don't know if we will escape from this entirely unscathed, but death now seems pretty unlikely. I used to, however, and I did sometimes fixate on what my precise reaction, both emotional and physical, would look like. Would I cry out? Run? Grab Alyson and collapse into a sobbing heap? I suppose there's no way to know what I will do, but if that little girl dies, I have a pretty good idea what her mother will do.