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”.

Day 0: Transplant Day

Last night I spent a lot of time talking to Maya about today, trying to prepare her. We knew that it would be necessary for her to wear a mask during her time here, and I wasn’t sure how that would go. So before bedtime, I took out the masks and gave her one, then put one on myself. I helped her get hers on, and she really didn’t fuss about it at all. She seemed to understand something was going on, and she was very attentive.

I explained to her that tomorrow we were going to go to visit baby Zoe for her new birthday, and she would be getting a new immune system. I told her that when people get colds or other things that make them sick, their immune system helps them get better, but that Zoe’s immune system couldn’t help her get better and so she needed a new one. Maya took all of that in very intently, and then asked if she could keep the mask to sleep with. We finished up our stories and said goodnight.

Maya during Zoe's Transplant

It always takes a little time to get her down to sleep, especially since we’re away from home. I went back in to check on her a little later, and she had all of her stuffed animals lined up on the bed, and she was making all of their boo boos better, one by one.

Earlier in the evening I had shown her how to kiss her finger, then touch the place where an animal had a boo boo, and told her it would feel better now, but I hadn’t given it much thought at the time. Coming into her room and finding her ministering to all of her toys was really touching. She had her mask on and was kissing her finger, then touching each one.

We all headed in to the hospital mid-morning, transplant was expected to be around 11:30-12. When we arrived, Zoe was all dressed up in her special dress ready for transplant day. The previous evening had gone reasonably well, she’s been improving slowly since our really bad days yesterday and Monday. A little bit of spitting up, but she was willing to nurse, and that seemed to make her feel much better.

Cord Blood Unit

Zoe’s transplant started at 12:30, and ran until around 1:15. Her procedure is┬ácalled a Hematopoietic Stem Cell Transplant, or HSCT. She received a unit of stem cells obtained from donated umbilical cord blood from the bank here at Duke University Hospital. The HLA typing for her unit was a 5/6 match, 6/6 being a perfect match, 4/6 or 5/6 being typical for transplants. She also received pre-meds of Tylenol and Benadryl to help manage any fever or allergic reactions.

They say that transplants are really uneventful most of the time, and thankfully that was our experience as well. It took about 45 minutes, and we all sat around talking, taking turns holding Zoe’s hand, and playing fun songs. Zoe’s blood pressure went up as expected, but she didn’t get any fevers or allergic reactions, which can happen.

The transplant itself is more of a transfusion in terms of what people usually think of as a transplant. Most of us think of a kidney or other organ and an operating room when we think transplant, but Zoe received hers in her hospital bed where we’ve been this past week.

Zoe during transplant

Her mood was pretty good, all things considered. Not a lot of smiles, but she remained awake the whole time despite the Benadryl, and wasn’t fussy or upset. We understand from the team here that kids often have a bit of a transplant honeymoon for a few days where they feel ok, then they may have some pains or fevers, and it can go up and down a bit until she has recovered.


From here on we’ll be watching cell counts every day. We expect she will remain at “<0.1” for awhile, but we want to see white cells grow. You’ll probably hear “Grow cells grow!” a lot from us.

As you probably noticed, we’ve been counting down the days from -23 to today, Day 0. Tomorrow is Day 1, and we’ll count up from here. Our goal is to see her cells graft and grow, counts to begin going back up, and then around Day 30 we’ll do a test to see what percentage of her cells are hers and what percent are donor cells. Assuming everything is going well, we’ll be looking toward Day 100 at that point, when we can return home.

It’s a long process. First Zoe’s life had to be saved from the active HLH, which thankfully happened quickly. Now she has had her conditioning and transplant. Next, her new immune system has to grow and we have to keep her healthy. After approximately a year, one year from today, she should be healthy enough to resume a normal life. Thankfully she is young and won’t miss the malls or crowded restaurants or school that she can’t go to but would miss if she were older.

For our family, it’s another step along the way toward being whole again.


Work-up Week is Over


Long week, but very satisfying in some ways because we now know everything about Zoe from head to toe. No more worrying about what we don’t know, now we only worry about what we do.

She’s been poked, prodded, scanned, zapped, scream-extracted, sound-tested, irradiated (twice!) and suffered no end of cheek pinches. The only thing that bothers her is her blood pressure cuff though, she’s a fantastic baby, calm through most everything.

In terms of test results, Zoe is overall in great condition. Sometimes it just seems amazing that she needs a new immune system, the rest of her is in pretty fine shape.

The three main test results we were still waiting for are back, her brain and sinus CT and her kidney function.

The brain scan was completely clear. No swelling, no “gaps”, no shrinkage, and it’s centered (which is something that had never occurred to me to wonder about). This is great, great news. I was deathly afraid that her prolonged exposure to steroids was having an effect, or the intrathecal medication (into her spinal fluid) may have had an effect on the brain, but it has not so far.

The sinus scan came back with a little cloudiness on her right cavity, which to be honest was no surprise. My side of the family has a grand tradition of sinus problems during pollen season, and Zoe has been sneezing and sniffling in recent weeks at the same time the rest of us were. They prescribed a bit of antibiotic which should clear it right up.

The kidney function test is called a GFR, and involved putting a radioactive but non-harmful chemical into her blood stream. Her blood is then drawn at 1 and 3 hour intervals (on the dot! they’re very intense about this). This allows us to know how much of the chemical is being processed through the kidneys and therefore how efficiently they’re functioning.

Zoe’s first GFR came back at 49, which is about half of what they wanted to see. There is a strong feeling from Dr. P that that number may not be quite accurate, but none of us will be surprised if it’s close. She has been on Cyclosporine for a long time now, and a higher dose than is sometimes necessary we’re told. That can reduce kidney function temporarily. She also has had high blood pressure for quite some time we think which is directly related to kidney function. We have fits because the only test she really fights is the blood pressure, she has chubby little arms and doesn’t like the squeezing, and between the struggling and the crying it’s hard to know if it’s ever right. From time to time we get one when she’s asleep, and it’s usually just fine then, if slightly elevated.

Regardless, the test came back low so we’re doing another one on Monday. We’ll know for sure then. If it truly is low, it won’t change our trajectory but it will mean possible adjustments to meds in some situations to ensure we’re not doing permanent kidney damage. From what I understand, what we’re seeing is likely temporary as a result of her meds and her kidneys should should make a nearly full recovery in time.

The rest of her tests for the week showed her to be a healthy little baby, with the exception of her immune system (HLH) and the kidney issue. Again, shew.

Next week we have the GFR again on Monday, a bone marrow aspiration and lumbar puncture on Tuesday. After that we have about a week off, then we begin her conditioning and countdown to the transplant.


More on Reduced Intensity Conditioning, Cord Blood, and HLH

A lot more information today. Some days it feels like we’re drowning in medical data and decisions. Michelle and I have been working through the options and doing our best to understand each path using our own research and what we learn from parents who have gone through this, which we then speak to our doctors about and clarify until we feel able to make a decision.

With regard to RIC, we’ve been going back and forth about using that or ablative/high-dose conditioning. One route is the more conservative route that has more successful cases behind it, but greater future danger for Zoe’s health and development. The other is much more modern approach with less patient data to point to, but can result in a very clean, relatively safe cure for Zoe’s condition.

We have pushed Dr. P and our nurse coordinator pretty hard for answers to every possible angle of this in the past few days. We’ve presented other cases of RIC/HLH/Cord Blood patients with very similar protocols but which were not successes and asked them to help us understand what will be different for Zoe. We’ve pressed them for examples of successes with this combination of factors. We’ve asked for numbers on Duke’s track record with this combination as well.

At this point we feel fully satisfied that, for Zoe’s case, for her current condition and the team of people treating her, RIC is the way we should proceed. It’s a tough decision, but this is the direction that feels right.

In recent years there have been a number of advances that will assist Zoe. The team at Duke was the first to do an unrelated cord blood transplant, and they do more than any other institution. That helps our confidence level as well.

Their process includes several additional medications to the standard protocol that help raise the chances of a successful graft, one of the concerns when using RIC with cord blood and likely a factor in the failure to graft in some patients in the past. They know now to continue GVHD medications longer than was once felt necessary, with past cases at various institutions proving clearly that stopping too early can cause the graft to fail.

What we’re seeing is that HLH is a relatively young disease and that, while the treatment phase is well established with the HLH-2004 protocol, the cure phase is still being perfected. This leaves a lot of fear and doubt, and the old saying that if you ask 5 doctors you’ll get 5 answers doesn’t help very much when it starts to ring true.

In the end we have to look at where Zoe is right now, and where medicine is right now, and do our best to make the right decision. Hopefully we have.

Reduced Intensity Conditioning & HLH

We’ve decided to go forward with the Reduced Intensity Conditioning (RIC) for Zoe. As I mentioned yesterday, it came up again in conversation with Dr. M, and after a long meeting at Duke where we discussed both the RIC and the “normal” or Ablative conditioning, we felt pretty strongly that this was the right approach.

Let’s back up a moment.

In our first meeting with Duke, we asked about the potential for a RIC process after doing a bit of research, but we didn’t have any cases to look at which were similar enough to Zoe’s to know if it was something that would work with HLH. At that time the idea was dismissed for the most part, since it’s not how they have done things with HLH patients, and they have had a good track record with their process.

Since then, we’ve spoken with or read about a few different cases where HLH patients took this approach, so we decided to bring it up again for consideration. This time the response was extremely positive, in fact Dr. P felt that it was the best approach having spoken to colleagues and done additional research since we first discussed it.

We’ve rewritten the plan entirely at this point.

About RIC

Reduced Intensity Conditioning is a process traditionally used for patients who cannot handle the standard ablative (high dose) conditioning in advance of a Bone Marrow or Stem Cell Transplant. It often involves an entirely different set of medications designed to achieve the same goal, but with less damage to the body.

The goal of the conditioning is to prepare the bone marrow for the new cell material, either donated bone marrow or stem cells. If the transplanted material does not take or “graft”, then the process has to be repeated or restarted.

Different diseases require different levels of conditioning. Some require the high dose or ablative conditioning to ensure that the disease is wiped out in the body before beginning. Others, such as immune disorders or non-malignant diseases, might require less intense conditioning since there is not something that has to be eliminated, rather the bone marrow is being prepared for new cell material. Partial elimination might be enough in these cases.

In short, ablative conditioning completely wipes out the bone marrow. RIC can either partially wipe it out, leaving some material but making enough room for the new transplant material, or completely wipe it out, giving the same results of the ablative therapy without the additional risks.

Advantages and Disadvantages

The advantages of RIC are numerous. For starters, all of the disadvantages of normal high-dose conditioning are reduced or eliminated.

  • The patient has less increased risk of future malignancy
  • Higher chance of remaining fertile
  • Reduced damage to the organs
  • Less chance of growth retardation and/or puberty delay

Disadvantages are few.

  • Chance of needing to repeat or restart the transplant procedure if graft fails
  • Longer conditioning process
  • Chance of relapse with some conditions or diseases

So why not do RIC? Well, a patient may not qualify for it due to their disease, or they may prefer to take a more conservative approach. RIC is newer and less tested, and the process is still being refined. Traditional conditioning is well tested and established, and it is a more sure approach in terms of the graft.


RIC has a relatively short history with HLH so far, due in part to the relative immaturity of HLH research. There are studies, and in some transplant hospitals they do RIC with HLH, but keep in mind that there are very few HLH patients in any given year. This makes it hard to accumulate results.

What sporadic results there are have been fairly positive, as best I can tell. Outcomes seem to be as good or better than ablative conditioning, and Dr. P confirmed our impressions in our discussion. Dangers still exist with any transplant: Graft Versus Host Disease and risk of infection are the two biggest and are no less dangerous on RIC.

Most of the existing studies I was able to find do not use cord blood stem cells as the transplant material however, making the specific combination of Unrelated Cord Blood, RIC and HLH exceedingly rare.

Zoe will be the first HLH case treated with RIC at Duke. They have treated numerous other conditions with RIC however, and the process is very similar. The medications are all well tested and established. The precautions are all in place for GVHD and infection as they would be in any transplant situation, and the team at Duke is great.

What does this mean for Zoe?

Zoe is in about as strong a position as any child could be going into a transplant with HLH. Her organs are in good shape, she has no fever, no other known infections. If there were ever going to be a successful case to do RIC with a cord blood transplant in an HLH patient, we like to think that Zoe is it.

This is a more modern treatment and gives her the greatest chance of walking away from this unscathed. I strongly suspect that HLH will be treated with RIC increasingly, given what I’ve been reading about the results. There just doesn’t seem to be a significant downside.

Worst case scenario related to RIC, she doesn’t graft and we have to start over with conditioning and a new transplant. Obviously GVHD and infection present other worst cases unrelated to the conditioning process.

This means we’ll be starting Zoe on Campath in a couple weeks in the outpatient clinic. After a week of that, she’ll have a week off, then we start the heavier chemo medications and Zoe will be admitted.

Our optimism is now at it’s highest point since we began this journey. We still have a hard path ahead, but we feel better than ever that we’re getting the best treatment we can for Zoe and that our advocacy is working in her favor.