Checking In

After last week’s lower immune counts we had skipped the VP-16 dose for the week, so today Michelle is in the clinic “catching up” a bit.

Zoe’s vitals are back up nicely for the most part, with the exception of her sodium and ferritin. Her sodium has been hovering at a lower than expected count, 127 (where 133-142 is normal), and the doctors are not sure why. Michelle’s sodium intake is quite low, so we’re going to take their advice and up her Gatorade (and junk food?) intakes. More bouillon cubes please!

The ferritin count is trending back upward, a worrisome sign. Ferritin if you recall is one of the markers for disease activity, so we want to see that trending down or remaining static, particularly as we look to move ahead on the SCT soon. We do not want to see disease activity right on the verge of starting her transplant process. Hopefully we’ll know more next week, they’re doing another count today and she’s getting the VP-16, which should have an impact.

There is some concern that we might be seeing the beginning of drug resistance in that ferritin reading, and the feeling is that we will need to move forward soon on the SCT if that is the case.

Feeling a bit tenuous here. Low sodium can mean hospitalization, high ferritin could be a warning sign of a return of the active disease. Better immune counts are our silver lining at the moment. I really want to see her go into her transplant with all systems in top shape.

Vitals for the week:

  • WBC: 9.1 (5-19.5 normal, this is way up thankfully)
  • SEG Neutraphil: 1.456 (also way up, a positive sign)
  • Sodium 127 (133-142 normal)


A Visit to Duke Part 2: Questions for a Transplant Doctor

On Friday we met with Dr. P, one of the Duke Medical Center docs who will be treating Zoe once we confirm her need for a Stem Cell Transplant. Prior to the meeting, Michelle and I drew up a list of questions which we had not been able to answer for ourselves, or couldn’t answer definitively.

I’ve left a few questions we asked off for personal reasons, but for the most part this list is complete.

It’s a testament to how well Dr. P covered the bases that, by the time he was done, most of our questions were already answered.

How have things improved since HLH-2004? I notice some stories/cases online with poor outcomes. Can you tell us about what’s improved in recent years?

Much has improved. New medicines and a better understanding of when to be aggressive and when to ease back have improved survival rates for HLH patients. In addition increased awareness allows for faster diagnosis; faster diagnosis means less harm to the body and greater chance of surviving a transplant.

We’ve found that the stories posted online tend to be those families who have suffered poor outcomes, unfortunately, making the picture appear slightly more dire than it might be. Dr. P confirmed that that was his experience too, more families who have lost children take the time to memorialize them online (with good reason) than do survivors.

Statistics? Rates of survival with newer procedures, cord blood, 5/6 match, infants vs toddlers

As discussed, statistics are skewed by the rarity of HLH and the inclusion of patients who did not benefit from recent advances in treatment. Typically pegged at 70%, rates of survival are likely much higher now when the disease is diagnosed early.

Cord blood offers reduced risk of Acute Graft Versus Host Disease, one of the two main risks of the transplant; it’s the best possible treatment short of a sibling match.

A 5/6 HLA match is very good; A 6/6 match would potentially offer a few percentage points more average success rate, but is generally very rare.

Infants tend to have slightly better chances of survival due to resilience and size — the transplant material is higher saturation in a smaller body, and higher saturation is good.

Has duke done any hlh patients recently? did they make it?

Since 2000 all HLH transplant patients have survived. Some live with side effects of the treatment and transplant and some are back to near “normal”.

Can we do a low-intensity transplant?

No. These are typically used for older patients who are unlikely to survive a normal transplant/conditioning regimen due to other health problems.

Is total body radiation necessary in non-cancer patients?

No. Zoe will not receive total body radiation, thankfully.

This treatment is more typical in cancer-related transplants or where there is a need for a targeted “nuke” to a malignancy. Zoe has a disease that would not be likely to be treated with external radiation.

Which meds are typically given for the conditioning regimen? (Campath? vp-16?)

Busulfan, Cyclophosphamide, and ATG.

Some patients get Campath as an alternative to ATG. Both use animals (gerbils? in campath, horses or rabbits in ATG) to incubate antibodies to help prevent transplant rejection. Both tend to involve some level of allergic reaction, but are nevertheless necessary. The allergic reaction is expected and treated as part of the conditioning process.

Zoe had a slight allergic reaction to vp-16 that was mitigated with benadryl, will she need something else if she cannot take high doses of that?

She is unlikely to need VP-16/Etoposide at all once the transplant process has begun.

Side effects — puberty, growth, physical disability, relapses?

Side effects are common and vary widely. Slowed puberty and slightly reduced growth are common. These are not as great as feared, however. The puberty issue can be resolved via monitoring and possibly some intervention if she is delayed, and the growth reduction is typically relatively minor. The example Dr. P gave was the cumulative effect of the treatment and her medications might cost Zoe ~2 inches in growth vs what her height might have been without. Her build/weight should be about what it would have been otherwise.

Her risk of cancer is elevated, something on the order of 2-3% higher. That means if she has a 12 percent chance of breast cancer in her life, she will now have closer to a 15% chance.

Neurological problems stemming from her treatment are possible, but are not as severe or likely as we feared. Examples given were trouble with higher math in high school or above, or need to utilize redundant study methods (taking notes and taping a lecture, for example, to help retention).

Severe disability overall is unlikely in a child like Zoe who does not have other underlying problems.

SCT should be curative, relapses of the kind a Leukemia patient might endure are unlikely.

Will Zoe need growth hormone or estrogen?

Very unlikely to need growth hormone. Might need estrogen if puberty is slow to start.

A lot of the poor-outcome stories I’ve read involve VOD — have any methods evolved in the past couple of years to mitigate the high chance of it, or is it still ~40%?

The risk of some VOD is still there, but new treatments using Defibrotide reduce the overall risk of death. So yes, methods have evolved and it is not nearly the risk it used to be.

Overall risk of getting VOD is closer to 10%, not the 30% sometimes seen in older literature, and the rate at Duke specifically has been only 5%.

We understand Zoe is a 5/6 match to the cord blood, a 3/6 match to Maya — are there any other donor options that could offer a higher match rate we should consider? Is a 5/6 match going to give her her best chance vs a ‘perfect’ match?

A cord blood 5/6 match is her best bet short of a better sibling match. No other donor options could offer a higher match. A perfect match would offer only a couple percentage points advantage.

What do we expect zoe’s physical condition to be at different phases — first 2 weeks, can we move her, hold her, can she nurse etc? after a month? after the 50 days?

The most difficult phase will be the first 2 weeks. We will be able to hold her and nurse her if she is willing, but she may not be willing for a period of time if she has mouth sores or poor appetite. She will be on IV nutrition regardless. Her condition should improve greatly by the end of the 45-50 day inpatient stay if she is on track.

Do parents room in with children? Is it best for there to be one person for the duration or can we rotate?

Yes one parent rooms in, and in fact a caregiver must be with her at all times. We can rotate caregivers.

Isolation: who can visit, family, room restrictions, can we bring in food, computers, etc.

Risk of infection is the driving force here, and the entire PBMT ward is in an “airlock” of sorts. Positive pressure, it’s called. When someone leaves, air only moves out of the ward, never in.

Visits are strictly limited to healthy people. Shoes must be wrapped, hands washed. Food is allowed (but no leftovers), as are computers and outside conveniences.

In the outpatient apartment, does she have to stay inside all the time? Does she have to stay inside for the year or is it only busy locations we have to avoid?

By the time the ~45 days have passed, if we are able to move to an outpatient status, she will be able to go outside and do most things. She will need to avoid busy places.

How soon should we move ahead? We understand that catching the disease early is very important to survival.

We have already gained control over the disease itself. The next step is to confirm the need for the transplant and then ensure Zoe is in the best possible condition to start. This should all happen in coming month or two.

A Visit to Duke Part 1: Surviving the Transplant

On Friday we traveled to Durham to visit Duke Medical Center and meet with part of the team there who will likely be handling Zoe’s Stem Cell Transplant. Overall it was a great visit, very positive and we gained a good deal of insight into the process.

Because of the wide-ranging nature of what we discussed, I’d like to break it up some and cover what’s going on with more than one post.

First, the SCT itself and what we now know we can expect.


Let’s talk a little about statistics. Briefly. Not my favorite subject either, believe me.

I have previously discussed the mortality rates for children going through a Stem Cell Transplant (SCT) based on both the research I’ve done and on the numbers I was given from Duke originally. As expected though, context helps put those numbers in perspective, and the outlook is not nearly as poor as we might have feared.

The problem is sample size — in this case, the amount of children who have had the procedure at Duke. The sample size for HLH is very small, and as such even one poor outcome skews the result vastly. Only 8-20 children are estimated to develop HLH per year, making it hard to get a clear picture.

I could say that 50% of the cars on my block are blue, for example, and that might be a true statement. But if there are only 2 cars on my block (2 in the sample), does that 50% begin to seem like a misleading number? In some cases, it might.

In the case of the SCT procedures done at Duke on patients with HLH, the number is 14. Of those, 5 did not survive long term. What we now know however is that there are a lot of factors that make that number less frightening.

  • All of the patients who did not survive long-term had their procedure prior to the year 2000
  • Since 2000, many things have changed with regard to medicines and procedures, reducing the risks
  • All of the HLH patients at Duke since 2000 have survived
  • All of the patients who did not survive have factors that distinguish their cases from that of Zoe or perhaps other more recent HLH babies.

Of the patients that did not survive:

  • One died in 1991, prior to both the HLH-94 and HLH-2004 protocols — his treatment was simply not as effective because not as much was understood about the disease, and he lost a long fight
  • One died of a fungal infection — since the time of that patient’s death, a medication called Vfend has become a standard part of treatment, and would likely have saved that child had they had that medication at the time. Zoe takes Vfend 2x a day.
  • Two died due to viral infections they had at the time of their transplant — that means they went into the procedure in poor health, likely because they had no other choice

My notes are incomplete on the 5th, but the overall point of the discussion at the time was that there were clear reasons that each child did not make it. It was not simply a matter of Russian roulette — these children were not at their best or were lacking medicines that, had they been born today, could have saved their lives.

Gives you new respect for medical research.

With this information in mind, the 70% survival rate begins to seem like a problematic number. The real number is likely much higher. The risks are still very much present, but we are no longer going into this feeling like our chances of losing Zoe are so high as to be soul crushing.


The two risks most on the mind of Dr. P are Graft Versus Host Disease and infection (bacterial, viral, etc). The risk of GVH is mitigated somewhat by the type of material to be used in Zoe’s transplant, cord blood. Cord blood procedures are understood to have a lower risk of Acute GVH vs. donated marrow procedures. The risk is there, but lessened.

The risk I had most been fearing was that of VOD, a specific complication of the transplant procedure. I have been living in fear of it due to the fact that several of the HLH children whose stories are public on the web did not survive it. I was greatly relieved to hear that Duke has access to a medication that takes much of the danger of that off the table. It is not FDA approved, however it is available to some hospitals on a “compassionate” basis. Duke is among the hospitals testing it, and they hope to see its FDA approval so that it will be in use more widely. Regardless, Dr. P felt confident that VOD would not be as risky for Zoe as it has for other children in the past.

So. 99% of patients survive the conditioning regimen. 90-95% of patients achieve a graft of the transplanted cells. Slowly, slowly, our fears are being replaced by facts.

Zoe will begin her procedure in the best health we can hope for while still fighting the disease — no known infections, good overall health and, by the time of the procedure, good counts (we hope). Risk of bacterial infection greatly reduced. Risk of GVH reduced. Risk of VOD greatly reduced.

Reasons for hope indeed.

Other Factors

There are a lot of questions we’ve been asking ourselves.

What can we do to help Zoe survive this?

Is she getting the right treatment?

Is Duke the best possible hospital for her transplant?

We want her to have every chance, so we regularly beat ourselves up trying to be sure we’re not making mistakes. The answers are hard to come by though.

What we know is this: we are doing everything we can for Zoe within our power. We are researching everything as best we can and challenging Zoe’s doctors (nicely! :)) when we aren’t sure of something, to be sure they are and be sure we understand why they are.

And, we now know that Duke is as good if not the best at pediatric transplants in the US. They do more unrelated (cord blood, marrow) pediatric BMT and SCT procedures than anyone in the country from what I understand. We feel we are in the best hands for the procedure that Zoe is going to have.

Ups and Downs

One thing we’ve come to understand about this disease from reading others’ stories is, you must be prepared for the ups and downs. It causes a lot of havok, and can generate swings in the body’s natural function.

We have been fairly lucky so far with Zoe, she has weathered it well all things considered. Here’s hoping that will continue.

Last week Zoe’s immune count marker (SEG Neutrophil) was up to 2.0 or 2000, this week it’s back down to .2, or 200. Not a good swing for us.

So this week we’re back in huddle mode, windows closed, no going outside for her to enjoy the beautiful weather until she has rebounded again. Dr. W felt it was likely due to the chemotherapy regimen, but we are wondering if she is not also struggling with her first pollen season.

In retrospect, it was probably a bad week to spend much time out, pollen in our region is still fairly heavy.

Vitals this week:

  • WBC: 3.1 (5.0+ is normal)
  • RBC: 2.83 (3.1+)
  • Hemo: 8.6 (9.5+)
  • SEG Neutrophil: .2 (1.0+)
  • Platelets: 250 (150+)

Rolling with the punches here.

Hopefully next week will be back to where we were last. We’ll have more to report about the outlook for her Stem Cell Transplant soon.

Right in the Middle

So, where are we?

First, a few updates. Zoe had a good day on Friday for her VP-16 dose. No adverse reactions this time, they gave her Benadryl at the start and did a 3hour drip instead of 2 or 4, and it worked out just fine.

Michelle was able to meet with Dr. W and the good new news is that Zoe’s immune system has made a sufficient recovery to put her out of immediate danger of infection from normal day-to-day life.

We are allowed outside. We are allowed to eat in (uncrowded) restaurants. It’s like Life 2.0.

The pertinent number, the one that gave us this new freedom, is her SEG Neutrophil count. Hers is 2.1, where 1.0-9.0 is considered normal. Great, great news.

Other vitals:

  • WBC: 6.2 (way up)
  • RBC: 2.73
  • Hemo: 8.3
  • Platelets: 447k

Where does that leave us?

Well, right in the middle I would say. We’re now mostly clear of the danger from the onset of the disease, and with continuing treatment we should stay clear for a little while. The fevers are gone, the organ enlargement is gone, the histiocytes in her spinal fluid are gone, and her platelets are well clear of the danger of internal bleeding now.

Once we have confirmation about the genetic testing, we will know more about the Stem Cell Tranplant, but we’re working on the assumption that she will need one to be cured. We have a huge decision ahead, depending on test results, as I’ve mentioned previously. It’s a little scary, but we feel considerably better than we did a few weeks ago. We know more now, and we’ve had more conversations with our doctors to answer questions we didn’t even know we had back when Zoe was sicker.

Our next step is to meet with the doctors at Duke, ask our long list of questions, and try to come to a firm decision about the transplant. That should happen late next week, and we hope to get news on the remaining genetic tests “soon”.

In the meantime we’ll be keeping up with Zoe’s meds, checking in twice weekly with the hospital, and hoping for continued improvement.

And I’m (not so) secretly hoping the chipmunk cheeks take a hike too.