Work-up Week Update

After yesterday’s post we got a lot of feedback, and today we have some new questions about the Reduced Intensity Conditioning and whether or not it will be right for Zoe. We’re working through those questions to be absolutely sure that we know what we’re getting into, and that the risks are acceptable. If we can’t do RIC, then we’ll return to our previous plan for full high-dose conditioning followed by a cord blood transplant.

Specifically what we’re trying to work out is whether or not the risks are too high to do a combination of RIC and cord blood. We’ve forwarded some questions for clarification along to the transplant team, and we’ll know more after meeting with them again tomorrow.

In the meantime, we’re half way through work-up week.

So far we’ve had several blood draws, EKG, Echo cardiogram, CT Scan of the brain, sinus, lungs, pelvis and abdomen, chest x ray, hearing test, crying capacity, and several meetings. Results have been positive for all her tests so far, with the exception of some low counts that have been a little low on and off for awhile (such as sodium).

We can say for sure that she has no disease or infection in her lungs, pelvis, and abdomen, that her hearing is fine, EKG is fine, and her heart is doing great. I expect we’ll see more results as the week goes on.

With regard to crying capacity, well, that was fun.

I don’t know if you’ve ever seen the movie Monsters, Inc., but the crying capacity is a little like the scene where the child is hooked up to a machine to extract her screams. No joke.

The nurse gets out a little pink plastic face mask with a tube that has an inflatable ring around the edge to maintain the seal and keep it comfortable, and then the mask is placed over the child’s face. It looks like a respirator or gas mask. We were told at the outset that 99% of children cry, but a deep sigh is still acceptable… right. I want to see the child that sighs into this little gizmo.

Zoe started off in her mom’s lap and the mask was placed over her face. She starts to cry, the machine hits 141, and the nurse takes the little mask off and says, “well the doctors usually want to see about 148, that’s about 100%, so 141 is 97% or so. That should be fine.”

Michelle says, “I’m pretty sure Zoe can do better than that.”

The nurse says,”Really…?”, I look at Michelle and ask, “Really?”. The nurse says, “Ok”, picks up Zoe and puts her in her lap this time. She holds the mask hovering over Zoe’s face, looks up at us a moment as if to say, “are you ready for this?”, then clamps it down nice and snug.

Zoe immediately gives a nice loud “WAAAH,” the machine flies up to 280, and Michelle says, “yeah!” like Zoe had just won a contest. We knew she could do it!

Zoe was calm again moments later, and we are now absolutely sure her lung capacity is what it should be.

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.

What I’m Reading Tonight

Today was a stressful day as the start of our transplant process. Duke’s team couldn’t have been better, but I think there was really no way around our being a little tense at the outset of this.

Among the topics discussed was the possibility of a Reduced Intensity Conditioning regimen. Originally we had thought this was ruled out, I brought it up specifically at our transplant Q&A, but it has come up again. Through discussions with Dr. M and closely following Maya G’s story, as well as some discussions with other parents via email, we continued to stir the pot a bit about the possibility of Zoe being a candidate for RIC.

As it happens, Zoe was a big topic of conversation in the PBMT team meeting, and one of the docs had recently heard Dr. Filipovich speak on the subject. Between our agitating and this coincidence, we’re now back to considering this procedure.

There is a lot to learn, and we have a big decision to make if she is a candidate. We’ll know more later in the week and I will cover the details, but in the meantime I am working through two journal articles on the subject for those hearty travelers who wish to follow along:

The Use of RIC in HLH and LCH Patients (2008 study)

RIC and ASCT in children with malignant and non-malignant diseases (2008)

Invigorating reading, let me tell you.

The Work-up

This week will begin Zoe’s transition to the care of Duke Medical Center, specifically the Duke Pediatric Bone Marrow Transplant unit, or PBMT. We have a total of 19 appointments this week, so we shouldn’t lack for activity.

For the benefit of those following and potentially other parents wondering what to expect in each stage of this battle, I’m going to cover our schedule for the week. I’ll also be doing my best to document our time from here on in detail, including with pictures where appropriate.

There will be scary moments in the coming weeks and months, and there will be pictures that will not have Zoe at her best. We’re keeping this journal for a number of reasons: to manage our own emotions and to communicate with family and friends, but also to try and give a road map for others who may find themselves with a child fighting for life and not know where to begin with it all.

I’m trying to create what I would have wanted to find that first night, when I went home with the diagnosis and tried to cope by reading everything I could get my hands on.


Check-in at the PBMT clinic:

  • Vitals taken
  • First lab draw, 1/2 of the blood needed for pre-transplant lab work
  • Respiratory vital battery & nasal wash (to check for virus)
  • Medical history review

Meeting with PBMT coordinator for education session
Meeting with the PBMT Social Worker for evaluation



  • Vitals taken

Meeting with Dr. P, primary transplant doctor for discussion


  • Hearing test
  • Crying Vital Capacities — study of lung function
  • EKG (heart study)


Check-in at Pediatric Radiology:

  • Chest x-ray
  • CT scan of the brain, sinus, chest, abdomen and pelvis
  • Echo cardiogram (heart study)

NPO for today starting at 7am 😦



  • Vitals

Check-in at Pediatric Radiology:

  • Kidney function test (GFR): dye will be injected into Zoe’s central line, then a tube of blood will be drawn at 1 and 3 hour intervals
  • Remaining pre-transplant labs drawn

Meeting with PBMT coordinator during GFR wait
Meeting with PBMT team at large
Meeting with Family Support Program
Meeting with Insurance Coordinator


Meeting with PBMT coordinator: Consents and Paperwork
Check-in at Duke University Eye Center for eye exam
Check-in at PBMT clinic for pre-operative screening consult


After this week, assuming all goes well, we will have at least one additional day of meetings next week to review. At that point the admission date will be set to begin conditioning and the countdown to transplant.

Zoe’s Development

I’d like to note a few things about Zoe’s development, since that is one of the things that can be affected by this process. The two main threats to good physical and neurological development are the extended use of steroids, and histiocytes in the spinal fluid doing damage to the brain if not caught soon enough.

Infant development is hard to put a finger on, since different kids do things at different ages, but it seems the best way to track it is after a certain point if she is not going x then we should be concerned, but we shouldn’t expect her to do x right at an exact time. The guideline I see most commonly is 3 months — if she is more than 3 months past due for a developmental step, we should look into it. It doesn’t necessarily mean a long term problem, but that’s the point at which we should be more concerned.

Zoe is 4 months old now, and generally at this age she should be holding her head up, resting on her arms when on her belly, smiling and moving her legs. She could be starting to try and turn over as well, from what I read.

With that in mind, right now we feel very positive about where she is. Zoe holds her head up very well, upright or on her belly. She still has a ton of extra weight on her face, and I am sure that that impacts her somewhat, but she is easily able to track people around the room, so it doesn’t seem to be affecting her too much.

She does well on her belly, usually propped on one elbow and one hand, and can keep her head aloft for a decent amount of time like that. She grabs toys, turns them around to look at different sides, and bats at them sometimes to make them jingle. She also has taken to throwing her arm across her this past week or so, which may be the first steps toward rolling over. To be honest, I’m not sure she will be strong enough for that for awhile, she has put on a pretty decent amount of weight from the steroids, but we shall see.

In terms of neurological steps, I’m not sure how well we can judge that yet. She tracks people with her eyes and moves her head when they get to far to one side. She laughs, smiles in response to seeing people she knows, and frowns when she sees something she knows she doesn’t like (like her med syringes). She has also taken to making noises in response to us when we are making noises and talking close to her, but I could be reading too much into that. 🙂

As best I can tell, we haven’t seen any problems yet. We still have a long way to go, but I am much more optimistic now than a month ago that Zoe will make it through without anything that would hinder her from having a perfectly “normal” life.