Two Steps Forward, One Step Back

It seems like the nature of treatment that we are never able to quite get clear of things before we have a setback. We progress, things improve, and then something happens and we are back where we were a few months ago in terms of medications and precautions. It IS improvement in a big picture sense, but it’s bittersweet and stressful day to day.

Zoe is back on track now, and our worst fears have been put to rest. She does not have a recurrence of HLH, her graft came back at >98% again, the same as before and a clear sign that her transplant has taken and HLH is gone (forever we hope). The fear of a return of HLH was due to a rash that appeared very similar to an HLH rash, but the chimerism result reassures us that is not the explanation.

GvHD Rash before treatment

She does however have GvHD, which has required her to restart Tacrolimus and go on a short term run of Prednisolone, the old nasty steroid, again. Why she has GvHD was a big point of confusion to us given her chimerism results, so I will do my best to explain briefly.

Zoe has a new immune system, and that immune system is completely donor material. This is the result we want, since her old immune system was dysfunctional and susceptible to HLH. Her new immune system however has not yet come to terms with it’s new home, meaning her old body is still considered a threat to it to some degree. When left unsupressed, her new immune system attempts to fight her old body, causing the rashes and other GvHD symptoms.

We had gotten her off of almost all of her meds slowly over months of weaning, when the rashes started to appear. It seems that she is not quite ready to be off of them, so we have restarted the routine and we’ll see where she is in another 3 months or so.

There is a question of whether or not she will be ready to enter pre-school this fall, but I’ve been told by reliable sources — Zoe’s two teacher-grandparents — that she is too young to need to be in school anyway. Yes it was what we had planned and yes it would be helpful, particularly socially, but it’s not going to hold her back to wait another 6 months or year to be safe.

In the meantime, she is back to looking good and feeling good most days, which is a relief. We are going to finally be able to remove her port despite the complications of these past weeks, so that too is progress. At this point I’m wishing that we had started putting little patches on Zoe’s well-worn diaper bag for each medical scare, not unlike notches in a gunslinger’s holster or emblems on a jet fighter. She’d have them racked up by now.



Day +65: Line Breach

We’re still waiting on the chimerism results. It’s a test that they like to discuss, and since results were not expected until this afternoon, we won’t hear about them until Monday. Crossing fingers that we’re at 100%.

Dr. P was very enthusiastic this week about Zoe, he feels that she has been a great case, given how well she’s done with everything, and that by her first birthday, she will be completely normal again. Rockstar is the word he likes to use. Normal is still the word that sticks in my head though, that’s essentially what we’re striving for here — a normal life for our girl.

Thursday’s labs looked good. No chemistry issues other than a drop in glucose related to her reduction in TPN. They’re working on weaning her nutrition so that we can get her off IV meds, the hope is that we’ll be on oral only before long and get her tubes out. A heel stick (blood test) came back normal for the glucose, so no worries there at the moment. WBC was at 3.4, which is where she seems to settle pretty often. She may drop again and need GCSF on Monday, but we appear to be out of the phase of stressing quite as much about that count. No one at the hospital seems worried about it, they’re much more focused on her chemistry’s at this point it seems.

We had our first true snafu this morning. We were closing up her lines (flush with saline, lock with heparin) after her night’s TPN, and when the tube was unscrewed her “cap” came off, leaving her central line open directly into her chest. The “cap” as it’s called is the barrier between her bloodstream and the big bad germy world — having it off for even a few moments is a bit scary. We do cap changes regularly, but we wear masks and Maya has to stay out of the room entirely, the cap is off for a matter of moments only while Michelle and I essentially hold our breath, so anxious are we not to have anything enter that line.

So having the cap come off and go unnoticed as it bumped around in her nightie is, well, not ideal. We noticed it was off when it was time to hook up her Tacrolimus, so it was a matter of a few minutes that it was open. A quick call into the hospital revealed that it was not something we leave unexamined and go on about our day, so Zoe had an unexpected trip to the clinic this morning.

At the clinic they did a line culture, which they’ll test to see if anything is growing in the line that could cause infection, and gave her a dose of Vancomycin, a fairly hefty antibiotic given preventatively in the case of a line breach. Hopefully nothing more comes of it, so far she has no fever or other symptoms of sepsis. That’s what we’ll be watching her for this weekend.

Having something like that happen really brings home how tenuous all of this is at times. Any little infection in her line can really cause huge problems. All the more reasons to get those things out of her.

On a lighter note, being back in Durham has given us a chance to revisit what we liked about the Triangle when we lived here. On Wednesday Maya and I went to (what used to be) Exploris, now known as Marble Kids Museum, and after about 2.5 hours of all-out-play-frenzy, took in an IMAX movie. Great fun. It’s a little strange to be a tourist in a place you used to live on the one hand, but on the other, we know some of the best spots already and can make the best of our free time.

Next week could be a big one. We’re hoping to hear back great news on the chimerism, get her off TPN, and potentially schedule a date to get her lines out. If we can move her Tacrolimus to oral, she will be free finally, having spent now 5+ of her 7+ months with tubes in her chest.

We’ll have to have a party. 🙂

Day +30: Chimerism

I had a post written up covering the last couple days while we were waiting for results, but now that I have them, those details seem less important somehow.

First the Chimerism test results, then I’ll try to explain them.

Zoe’s test came back at “Greater than 98%”, which is as high a reading as this particular test offers. That’s good news. The best news, really.

Also important is the line on the report that reads, “no recipient cells detected”. This means that she has none of her old immune system left whatsoever. In short, Zoe’s test results were the best she could get on this test, and the best news we’ve had… well, ever, I suppose.

What does all of this mean?

Zoe “has” (we can’t say she’s cured yet but we’re well on our way) a hereditary condition/disease called HLH which caused her immune system to malfunction and attack her body, as if her body were an infection. The inflammation from this attack caused persistent fevers, enlarged organs, and without treatment and subsequent cure would have resulted in her death in a matter of weeks.

To cure Familial HLH Zoe had to get a new immune system via either a stem cell transplant or bone marrow transplant, otherwise the disease would continue to re-activate. Eventually the drugs used to control it would become ineffective, leaving her defenseless.

In order to get a new immune system, the old one has to be wiped out via a series of drugs (chemotherapy) that destroy the old bone marrow (which produces the white and other blood cells), so that a new one could be transfused. When a transplant takes place, there is a chance that both the old cells and the new cells will co-exist for a time, until either the new cells establish “dominance” as it were, or the old cells reject the new ones.

This rejection is the greatest risk for these kids. If it occurs, they have to go through the process of transplant again until they can establish a new functioning immune system. They can live with a mixed immune system, however, so long as the “dominant” portion are the new cells. Specifically, the old lymphocytes must be destroyed, if they continue to be produced in the marrow they could potentially begin attacking the body again.

This mix of old and new is called Chimerism. The word comes from the Chimera, a creature of Greek myth composed of multiple types of creatures. The test itself tells us what percentage of the old system still exists, and what percentage is new. We want as much as possible to be new, and in Zoe’s case, it appears that it is all new. She doesn’t appear to have any Chimerism, she simply has an entirely new immune system.

I am told that kids can do just fine with as little as 20% new cells, again assuming that the trouble-making lymphocytes are gone and that portion of the immune system is governed by the new cells. We had been optimistic, hoping for results greater than 50%, with room for growth toward that 100%. As time goes on after transplant, it’s expected in kids with a mix of old and new that one of the systems will continue to establish itself, and that they could eventually end up with 100% new cells, despite starting off with 50 or 75% at day +30. This is all part of the process.

Dr. P mentioned that he had been privately expecting and hoping for a 90/10 split for Zoe, due to the reduced intensity regimen and the fact that it can sometimes only partially wipe out the old cells. He would have been happy with that result. He was very pleased indeed with this result. Zoe’s RIC was on the harsher end of RIC, but I now firmly believe we got the best of both worlds.

Zoe was able to receive a lighter dose of the chemotherapy, potentially preserving her fertility and protecting her from the harsher side effects, while still seeing the “right” amount of destruction to her old immune system, leaving her able to accept the new cells successfully.

We will be eternally grateful to Duke University Health for the successful transplant, and to Wake Forest University Medical Center for her early diagnosis and life saving treatment. I now know which basketball team I’ll be rooting for for the rest of my life.

We don’t yet know all the ramifications of this for us or for Zoe. We know we will still need to maintain long term care for her, protect her from infection this next year through isolation, and watch her for GVH. Nothing in medicine is 100%, there is still a chance that there could be GVH or other issues, but we believe the chance much lower than it would be with a more mixed Chimerism.

Our next goal is to reach 60 days, after which the risks to Zoe for infection or GVH should be drastically lower than they will be these next 30 days. The worst is now firmly behind us and I hope that very soon we will be able to say that Zoe is cured. After this year has passed, our family should be able to return to our “new normal”.