Friday, October 22, 2010

UMinn for Transplant

Yesterday evening, Sarah and I learned that our HMO had approved our request to have Ethan's second transplant done at the University of Minnesota Children's Hospital.  This is a big turn around for us as we had long thought that we would stay in Portland at Doernbecher's Children Hospital.  The decision brings with it at once more hope for a successful transplant and more uncertainty about our life in general.  

We have known for a long time that UMinn is generally regarded as the foremost Hurler's center in the country.  They do far more transplants there and are on the leading edge of research into new treatments and therapies.  Through Ethan's first transplant and in preparing for his second, we asked doctors here and doctors there if there was any difference in protocols and outcomes between here and there.  In response, we heard that the protocols are widely agreed upon and that there isn't enough data on outcomes to point to any meaningful difference.

Then a few weeks ago we got some new information from an unexpected source.  I was on the phone talking with Dr. Klane White at Seattle Children’s Hospital about that hospital's MPS team and the advantages and disadvantages of seeking Ethan's post-transplant Hurler's care there.  Dr. White is a unique individual in the Hurler's world.  He's an orthopedic surgeon whose daughter Susanah suffered from Hurler's, went through two transplants, and most unfortunately passed away at age 9.   Dr. White is also on the board of directors of the National MPS Society.  So, Dr. White's seen this disease from just about every angle.

After talking about the MPS team at Seattle, the conversation turned to Ethan's second transplant.  Dr. White told us frankly and explicitly what no one had told us before, that there may be general agreement on the transplant protocols, but there are a range of potential post transplant complications that are Hurler's-specific. Patients often need an experienced Hurler's transplant team to interpret what's going on and to respond effectively.  He also told us that from what he knew, the transplant outcomes at UMinn, while certainly not guaranteed, are the best in the country.

Sarah and I had long ago decided that we would push for a referral to one of the big MPS transplant centers if we got information that it would make a difference, and suddenly we did.  For us, there's no way that we couldn't act on that.  If Ethan dies from transplant complications, we need to know that we did everything we could, that we gave him the best chance. There's just no other way to look at it.

And yet, even though we're comfortable that it's the best decision we can make, I think we're all scared by the change.   At best, it will be a 3-4 month stay in Minneapolis.  At worst, if significant complications develop, it could turn into 6 months or longer.
We know that the four of us will go out together, that we'll continue to fight this disease as a family.   But Caleb is scared about changing schools, and we are scared about trying to juggle our jobs and responsibilities here in Oregon for an indeterminate length of time from Minnesota.

For Caleb, I know this change will be difficult and stressful, but, there may be a good side, too.  The Ronald McDonald House Twin Cities has a K-12 school program on the property for patients and their siblings.  I think it would be really good for Caleb to be able to spend some time with other kids who have brothers or sisters who have serious illnesses.

For Sarah and I, a lot of our uncertainty comes down to whether or not we end up having enough FMLA time to get us through the hospitalization period.  We're both extremely fortunate to have very good and supportive colleagues and organizations behind us, all of whom have done everything they can to provide as much support as possible.  And both organizations have been very helpful in working out telecommuting agreements.  However, we both used up a lot of regular leave and FMLA over the last year.  We think we will be able to make arrangements so that we'll have enough leave for a 3-4 month hospitalization.  But if it goes beyond that, we may need to make some very difficult decisions, both for our sake and for the sake of our employers.

Last time, we tried to telecommute from the hospital.  That worked okay because we had great help during the day, so that Sarah or I could go to another room and work.  I will say that it was pretty surreal at times going from a discussion with the doctors about Ethan's latest complication to a phone call from a colleague at work asking a question about something that seemed a million miles away.  But we knew then that about 20% of kids need a second transplant, so telecommuting allowed us to shepherd at least some of our leave up to this point.

This time, I've decided that I can't telecommute while he's in-patient.  I just can't keep those plates spinning at that point, and need to be focused entirely on Ethan.  So, I've worked it out with my office that I'll take about 9 weeks of leave, which will hopefully get us through the in-patient period, and then telecommute after that.  If Ethan is in the hospital longer than 9 weeks, then Sarah will take leave when mine runs out, and we'll go from there.

After he's released from the hospital, there will be a period of, I'm guessing, a couple of months, where we're checking in at the hospital 3-5 days a week, and he will almost certainly be readmitted at least once or twice due to complications, before it's all said and done.

Logistically, I think it will be okay.  Our biggest concern are our two dogs.  The reality is that with all of the demands on us, the dogs are a challenge at the best of times.  I'm not quite sure what we're going to do with them now.  Unfortunately, our dogs are humane society dogs and both of them have their own "issues".  Neither of them likes other dogs, one of them doesn't particularly like kids, and the other one is just generally neurotic.   Sarah's folks have offered to take them while we're gone, but they have an elderly dog of their own, and our dogs don't play too nicely with theirs.  I think we’re planning on trying them out with some supervised visits to see if maybe they might get used to each other, but if they can’t settle in together well, having them in the same house together for some period of months would be less than ideal. And most of the other "dog" people that we know who might take them, have dogs of their own already, so it's the same kinda thing.

Personally, I'd think our best option is to give the dogs to the humane society to see if they can be placed separately in new homes. But they're 12 and 11 years old, and between their age and their issues, I'm not hopeful that they would find new homes easily.

Aside from that, I think we'll be okay.  It looks like we're going to drive out--Oregon to Minnesota in the middle of winter should be an adventure in and of itself.   We were talking about a late December/early January admit with the team at Doernbecher.  I think UMinn will want to keep to that schedule, but we've got a teleconference scheduled with them on Monday and will know more then.

I also expect that one of us will fly to Minnesota with Ethan at some point in November for a full pre-transplant work up.  But again, we don't have any specifics on that yet.  

In other news...
Ethan's ear infection reoccurred, so we're keeping an eye on his ears.  And Ethan's been on steroids to combat the anemia.  The steroids have screwed with his sleep schedule, so we're taking turns sleeping with him in the guest bedroom.  The steroids have also caused him to pack on a lot of weight.  When he was admitted for the anemia two weeks ago he weighed 30.5 lbs, two days ago he weighed 34.8 lbs.  Time to break out the next size up of Caleb's old clothes!

But aside from that both boys are doing great.  We got down to Silver Falls State Park last weekend for an annual family get together, so they got to run around with their cousins.   Caleb's doing great in kindergarten and keeps bringing home "Viking Victory " cards from the teacher saying what a great job he did. Ethan's not talking too much more than he used to, but a few times a day he'll give us a word.  Yesterday, when I picked him up from daycare, I was greeted with a great "Daddy!" which was wonderful to hear.  And if you ask him if he wants a cookie, the "yes" that you'll get in response has become a lot more clear.  This morning’s word was “book.”  And about every other weekend, Caleb's got a birthday party to go to or a play date, so we're all having fun!

Caleb's outfit for the first day of school.  He picked it out himself.
(We tried to warn him!)

Friday, October 8, 2010

Hospital Wrap Up

During Ethan's nap yesterday, we got the word that we could head home.  

Here's what the docs are telling us.  Ethan has autoimmune hemolytic anemia.  That sometimes occurs when there are antibodies in the blood, those antibodies attach themselves to red blood cells and then the body's immune system attacks the antibodies and destroys the red blood cells they are attached to.  The loss of red blood cells cause the anemia.  And when the red blood cells are ripped up by the white blood cells they release bilirubin which impacts the liver and causes the jaundice.

The docs say that there are a couple of possible causes,  the antibodies may have developed in response to a virus.  Or they may have developed in response to the amoxycillan that Ethan was on a
couple of weeks ago to fight his ear infection.  They also say, that this was not related to his transplant  or to his Hurler's and that anybody might have developed this.   

If it was caused by a virus, then Ethan may go through this again if he gets whichever unknown virus again.  If it was cause by the amoxycillan, then he may get it again if he's given amoxycillan or
other penicillin bas drugs in that class.  The head hematologist we've been working with, tends to think that this was in response to a virus because Ethan had been off of the amoxycillan for 8 days or so before getting jaundiced.

But we don't really know the cause.  If it was in response to the amoxycillan, then there are a couple of things to consider.  First, penicillin based drugs are not typically part of the bmt drug protocols or typical responses to transplant infections or complications.  So, it's very unlikely that Ethan would be in a position where he might get one of these drugs and hen have to fight a reaction while he's weakened during transplant.  Second, unlike an allergic reaction which might become more severe over time, this reaction wouldn't be more severe.  So we may give him one of these drugs in the future both in response to a bacterial infection and to see if he develops a reaction and if that was in fact the base of all of this.

Ethan's done very well throughout this.  His energy was low on Tuesday when we came in, but he was anemic so ya got to give a kid a break.  He had two have units of O- blood overnight the first night,  with the transfusions they gave him benydril each time to reduce the risk of a histamine reaction, but that also conked him out.  Yesterday afternoon he had enzyme infusion, and as they normally do, they gave him benydril with that as well.  

Playtime after dinner.

After we both woke up from our late afternoon nap, we went over to the playroom where the Candlelighter's Children's Cancer Society (we were in the hematology/oncology ward) had brought in pizza for dinner. 

He got so much sleep on Wednesday from all of the benydril that he (and I) were both still awake with his primary care pediatrician came in just before 10p.  (Dr. Oltmans works up at Doernbecher every couple of weeks.)  It was good to see her, and as always in working with her, she translated a lot of the specialist talk down to a concerned parent level and she raised some questions that we both needed to follow up with the hematologists about.

In and amongst all of this, we've been battling diarrhea, AGAIN, for the last 10 days or so.  We went through a month of diarrhea when he had adenovirus in July and August.  So none of us are thrilled to be back to the multiple blown out diapers and multiple changes of clothes each day.

Ethan in all his glory!
The docs aren't sure what's causing the diarrhea.  They tend to think that it might be caused by the same mystery virus that brought on the anemia.  I think the diarrhea is graft vs host related.  We started tapering Ethan's first immunosuppressant drug in August.  Since then he's developed GVHD rash on his skin.  We started  tapering the last immunosuppressant a few weeks ago and to my mind the track of the diarrhea roughly corresponds to the lower level of immunosuppressants that had been keeping GVHD in check.   I will also say that the look of the diarrhea is similar to what we saw when he was dealing with GVHD immediately post transplant.  But y'all don't need or want me to go into much more detail about that.

They put Ethan on a  course of steroids to help fight the hemolytic anemia.  The steroids are supposed to help suppress his immune system so that his white blood cells stop fighting the red blood cell+antibody combination.   If they suppress his immune system, the steroids may also reduce the severity of his GVHD, so if that's what's causing the diarrhea, it should help make it better. 

The picture above, was taken during one of Ethan's many wardrobe changes.  It cracks me up, and I've got to save it to show to his prom date.  Beyond that, it's kind of an interesting picture because you can clearly see his hickman, his umbilical hernia and his knock-kneed stance.  The little muscle shirt thing he's got on is actually a rubber sleeve that they sometimes put on people's arms when they've got an IV in order to keep the line in place.  In this case, the nurses took the rubber sleeve and cut two arm holes in it.  We put it on him because he'd gotten some dirt under his port dressing a few days ago and had been scratching it even after we cleaned it and changed the dressing.  That little net thingy  did a great job of keeping him from messing with it or scratching.  But it just looks so wrong!

Anyway, we got home yesterday afternoon.  I went to bed right after dinner and slept straight through.  Sarah, Ethan and Caleb are at home today.  Ethan's got to go up to the hospital for blood work this morning to make sure that his red blood cell counts have stayed up and that his bilirubin numbers are still declining.  They expect that everything will still look good, so it should be a quick trip.  

Thanks for checking in on us.

All the best,
Todd, Sarah, Caleb and Ethan.

Tuesday, October 5, 2010

Autoimmune Hemolytic Anemia

Hi guys,

Well, Sarah and I were just saying how lucky we'd been that Ethan hadn't been admitted *overnight* for any major medical issues since he was discharged post transplant last year. Well, the fact that we were in the Doernbecher ER at the time, should have been warning enough not to tempt fate.

Late this afternoon, ethan's daycare provider call us to say that he appeared jaundiced. And sure enough when I got there 30 minutes later, he was a little yellow, and his eyes were a little yellow, and his lips were a little pale. So we talked with his docs and they said to bring him in so they could have a look.

You know what they say, just because you're paranoid doesn't mean they aren't out to get you? I guess we weren't too paranoid...

Ethan's been admitted to receive treatment for hemoplastic anemia, essentially he doesn't have enough red blood cells right now. There are a few things that could cause this, something to do with the transplant, may mean that his body isn't producing enough blood, or blood cells are getting torn up as his body attempts to fight antibodies that have built up in his system, or he might have a bacterial infection (c-diff), or he might be loosing blood somewhere.

At the moment, the docs are looking at the antibody issue and the c-diff as the likely culprits. As I understand it, the antibody's are formed in response to drugs like the Amoxcycillan that he just had for his ear infections. I think what happens is that the antibodies attach to red blood cells and then the white blood cells attack the red cells because these antibodies are attached.

The C-diff is a bacteria that forms in his gut in the absence of other bacteria. They say that it is sometimes found in immune suppressed patients and sometimes develops in patients that are coming off antibiotics.

So, the deal is that they're running some tests and we should know more in the morning. In the meantime, they're going to give him some blood overnight. If all goes well, we may be here two days or so while they get things under control.

Coincidentallly, Ethan and I were actually scheduled to be up here tomorrow anyway for his enzyme, so our schedule hasn't changed that much!

By the way, a note about the new blog site. I'm hoping to stop posting to the caringbridge site and start posting here. This site has a few advantages over caringbridge: it'll be easier to upload pictures and video on a regular basis, and we can respond to comments on posts directly. So often, someone will leave an informative or supportive post, or will have a question about Ethan and we haven't been able to reply to that person very easily on Caringbridge. Hopefully, we'll be able to do so here.

I've transferred over all of the posts from the old site, but unfortunately, there's no way to transfer the guestbook comments. So we'll leave that site live so we can go back to those.

And finally, I think Sarah and I have figured out how to explain MPS to Caleb. We've been struggling with this for a year, how do you explain a complex, multi-system, degenerative genetic disorder to a five year old?

Here's what we figured out. Imagine your body is a house. Every time the trash can fills up, you take the full bag out and put it on the floor in that room. Before too long, the room would be full of trash bags, and you wouldn't be able to get around. That's a pretty good analogy for what's going on with our busy little guy.

Thanks for being there. We'll write more as we learn more about Ethan's condition.

-Todd, Sarah, Ethan, and Caleb

Friday, October 1, 2010

Wednesday, September 29, 2010

Ethan's chiimerisms are down to 13% donor. Dr. Nemecek is officially saying that the bone marrow engraftment has failed and we're going to a second transplant, probably in January. 

The initial donor search has been done. There are a good number of 6/6 adult donor matches and one 6/6 cord blood match. Six out of six is considered a perfect match. However there are an additional six markers that they will try to match. They are starting to call in adult donors to do a screen on that second set of markers. 

Ethan's first transplant was a reduced toxicity regime in an effort to reduce the chance of mortality from the regime itself. Reduced toxicity regimes don't seek to remove all of the host bone marrow, only enough to clear out enough space for the donor cells. This second transplant will be a full ablative, full toxicity regime. 

The risks are significant. Typical mortality on these transplants is 30%. But Ethan is a very strong little boy, and I'm hopeful and confident that his odds are better than that.

It's a long time between now and January, and there will be more to share and talk about over the coming months.

In the meantime, we will play and learn and enjoy.

Love to you all,
Todd, Sarah, Caleb and Ethan 

Friday, September 17, 2010

It’s been over a month and a half since we last updated Ethan’s journal. That’s probably the longest we’ve gone between updates. That certainly comes primarily from the fact that Ethan’s condition has been stable, but perhaps equally from the fact that we’re all settling into a routine and learning how to live with MPS.

Day to day, Ethan’s doing good. He’s strong and he’s happy and brings joy to our lives.

Ear Infection
Just yesterday afternoon, Ethan was diagnosed with severe ear infections in both ears and has been prescribed a course of antibiotics. 

Ethan does have ear tubes and it looks like they are working properly. We think that Ethan’s new hearing aids caused a build up of wax in his ear canals and kept the fluid from draining. 

Ethan hadn’t spiked a fever and he didn’t seem to be in pain, it was really just luck that we caught it. Yesterday morning, Sarah’s parents took Ethan in to get new ear molds fitted for his hearing aids since he appeared to be outgrowing the old ones. During that process, they did a pressure check on his ears and the results of that seemed off, so we took him into to his pediatrician for a check.

Ethan’s been going to speech therapy once or twice a week since mid-August. (Thanks very much to those who have helped and offered to help with picking up and dropping off Ethan for appointments.) 

The speech therapy sessions help some, but--with due respect to the speech pathologists we work with--I think the speech training is rather like obedience school for one’s dog. If you’ve ever taken your dog to obedience school, then you know that the school trains your dog a little bit, but mostly trains you how to train your dog. That’s pretty much speech therapy. It’s about 1/3 about working through words and sounds with Ethan while we’re playing with him and about 2/3 about teaching Sarah and I how to teach him. We are seeing measured progress though. Ethan’s picking up a few more words and sounds over time. He’s got “Me” down pretty well (as in “give it to me!” and “me do!”, and he’s working on “mine” (which is a complete sentence on it’s own, isn’t it?). He’s working on a number of other word approximations and his pronunciation is getting clearer day by day. 

We’ve been working through a question about soft-orthotics. Ethan’s early intervention physical therapist recommended them, but his orthopedic doctor had never even mentioned them, and when asked said they didn’t think they would help much. That sent me off on a search to see if there were any orthopedic recommendations for Hurler’s and whether or not they would be worthwhile. The doctors seem skeptical and the physical therapist is strongly supportive. We were able to get a prescription for them, so I think we’ll give them a shot under the “what the hell, couldn’t hurt” medical philosophy.

Ethan’s transplant chimerisms continue their slow and steady decline. In July, he looked to be about 25% engrafted. The August test showed that he was about 20% engrafted. If his engraftment drops to 10% then we’ll do a second transplant. 

We have finally started tapering Ethan’s immunosuppresent drugs. The immunosuppresents help keep his body from rejecting the donor cells so that the donor cells can engraft. As he goes off of the immunosuppresents, there are three possible outcomes: 1) the chimerisms and the engraftment can crash entirely, 2) we’ll continue to see the same steady decline or 3) things might stabilize. He’s come off of the CellCept, and he’s on a long taper of tacrolimus that will continue into November. 

I think we all expect that Ethan’s chimerisms will decline pretty quickly once the immunosuppresants are removed. In that case, we’ll move to a second transplant within the next few months. But the risks associated with transplant are still huge, so no one’s going to rush into that if we don’t have to.

Living with Hurler’s
We’re now a couple of months past the first anniversary of Ethan’s diagnosis, and we’re approaching the first anniversary of his transplant. The last year has been incredibly difficult on all levels. On the transplant side Sarah and I and Ethan’s grandparents have been supporting and providing Ethan’s medical care, both at home and through multiple hospital stays. On the Hurler’s side we’ve had numerous medical assessments and tests on essentially every part and system of his body trying to determine the damage to his body and mind from this terrible disease. And personally, Sarah and I have been in a year long sprint to learn as much as we can about the care, treatment and long-term issues and prognosis for Hurler’s kids. 

Clearly, the transplant issues and concerns and time commitments will be with us for some time to come. However, some of the other pieces are becoming less frenetic and time consuming, at least for the time being. 

After a lot of reading of reference articles, medical papers, traveling to the MPS center at UMinn and the reading stories of countless other Hurler’s kids, I think Sarah and I are now reasonably comfortable with our knowledge of Hurler’s: how it has and will continue to impact Ethan’s life and the processes and standards of care that we and his doctors can provide. Hurler’s is such a rare and complex disease that we know that we will always have to be Ethan’s strongest advocate. We know that together with his primary care physician, part of our job will be to set an expectation of strong and aggressive treatment and to help put all of the pieces of Ethan’s health care puzzle together so that each of the various specialists can see beyond his individual conditions to consider and treat him holistically. 

We understand that we don’t have all of the answers and that that there will be a lot of maddening complications, vagaries and difficulties along the way; but, it doesn’t feel like we’re stumbling blindly along in the dark anymore. I wonder if we’ve now reach a predictable plateau, much like one of the “stages of grief”, that all families come to eventually. If stages of response to this kind of thing can be mapped, I sometimes wonder what lies ahead, but then again I’m not sure that I want to know.

Ethan’s Long-Term Prognosis
I’ll leave aside, here, any discussion of Ethan’s prognosis should he need to go through a second transplant. If and when we come to that, there willl be time to discuss it. Now that we’re through this first year of learning about the disease and Ethan’s current state of health, where are we? Assuming that Ethan’s current transplant holds or that a second transplant is successful, here’s what we think we know.

Life expectancy. The oldest Hurler’s patient that I know of just became a senior in high school. He received his transplant when he was 3, so that would have been about 1996. Though research leads me to believe that there are some Hurler’s kids who have lived into their 20s. There have been a number of advances in Hurler’s treatment since then and hopefully there will continue to be more. It is entirely possible that with advances in medical technology that Ethan might live into his 30s or 40s or even beyond. But the current harsh reality is that many Hurler’s kids who survive transplant die before age 20 often from a combination of damage to internal organs that Hurler’s does both before and after transplant.

Orthopedic Issues. After a successful transplant, orthopedic issues will be the single largest area of concern and medical interventions over the course of Ethan’s life. He currently has spinal kyphosis on his back, pectus excavatum on his front, joint extension issues in his elbows, knees and angles, and hip issues. It’s also likely that he’ll develop carpel tunnel syndrome sooner or later. He is likely to go through orthotics, braces, and multiple surgeries his wrists, hips and spine. 

Neurological Issues. Assuming a successful transplant outcome, Ethan should do okay neurologically. Without a successful transplant, the GAG waste products will build up in his brain and Ethan will regress, forgetting skills that he already knows, until he is in a vegetative state. 

Cardiac Issues. Cardiac issues centered around the heart valves are a primary systemic issue with Hurler’s disease. Ethan had an echocardiogram last year and a follow up last month and both showed he has normal heart function. However, Ethan will always be at risk for developing potentially fatal heart irregularities and will need to monitored at least yearly. 

Vision Issues. At this point, Ethan suffers from mild corneal clouding. That may worsen over time, in which case he’ll need a cornea transplant in one or both eyes. 

Hearing Issues. Ethan current suffers from mild to moderate hearing loss in the mid to upper ranges, respectively. His hearing will not improve over time and I expect it will get at least slightly worse as he gets older.

None of the above is offered in order to solicit pity either for Ethan or for us. We know there are so many families fighting other types of MPS/ML, and other lysosomal metabolic disorders like MPS, for which no treatments currently exist. Those families walk an extremely difficult path and our unwavering love and support goes out to them. 

They say that a receiving an MPS diagnosis is a life changing experience. That has certainly been true for us. Fighting this disease will continue to be a significant part of our lives for--hopefully--decades to come. I included this summary because I wanted to give you an update on the results of all of the assessments that Ethan has been through, and because I wanted to help our friends and family understand the fight that we’re engaged that has become a such significant part of our lives.

Thanks for your love and support over the last year. It does make a difference.

Todd, Sarah, Caleb and Ethan 

Friday, July 30, 2010

Minnesota Trip Recovery Day +3

Our trip to Minnesota was a quick and tiring whirlwind, but overall helpful and worthwhile.  We learned a little more about evaluating the need for a second transplant, and got some good news and good recommendations about Ethan’s mental development and treatment needs.  We also made some decisions about where to do the second transplant if it’s needed and about Ethan’s long-term hurler’s care.  We’re also wondering if there’s anyone in the area who can help shuttle Ethan to/from some upcoming speech therapy appointments? (See the end of this post for details.)

We arrived in Minneapolis late afternoon on Saturday, and checked into the Ronald McDonald House a couple of blocks from UMinn.  On Monday morning we met with Dr. Orchard, head of the metabolic disorders transplant unit at the University of Minnesota Children’s Hospital.  We reviewed Ethan’s history and Dr. Orchard examined Ethan.  Dr. Orchard noted the range of issues that we’re already aware of slight corneal clouding, spinal kyphosis, various orthopedic issues, but didn’t highlight any area as being out of the norm or requiring immediate intervention.

On the transplant side, we discussed the current state of Ethan’s chimerisms (20-25% engrafted) and the implications for his neurological development and a possible second transplant.  

In previous posts, I’ve talked about the fact that it’s impossible to measure the amount of enzyme in Ethan’s brain.  I’ve also talked briefly about the fact that there is an attenuated version of Ethan’s disease called MPS 1 - Scheie and that people who suffer from Scheie have greatly reduced levels of enzyme in their bodies but do not suffer any neurological deterioration.   All of which raises the question of how much enzyme Ethan’s body needs to produce naturally in order to avoid neurological deterioration?

We talked to Dr. Orchard about this, and his response was somewhat helpful.  He said that the level of enzyme in Ethan’s body is not necessarily the same as the amount in his brain (seeblood brain barrier). Hurler’s syndrome is caused by mutations on the gene that is responsible for the production of the alpha-L-iduronidase enzyme.  According to Dr. Orchard, there are different types of mutations that can occur on the gene, and while the mutations will result in Hurler’s syndrome, the variations can result in different severity of symptoms and different levels of enzyme production in the brain in a mixed-chimerism patient like Ethan. 

That basically means that in the short-term we look primarily at Ethan’s transplant outcomes to guess whether or not he’s getting enough enzyme in the brain.  We assume that if his engraftment is strong and his body is producing a reasonable amount of enzyme (as measured in his body) then he’s probably getting enough in his brain.  

In the long-term, we use scheduled neurcognitive development testing to assess Ethan’s development.  If his development is progressing, we assume that he’s producing sufficient enzyme, if he’s not developing or starts to regress, then he’s not producing enough. 

With all of this as background, Dr. Orchard agreed with Ethan’s Oregon transplant team that in the short-term the chimerism numbers will drive the decision about whether and when to do a second transplant.  In other words, if his chimerisms get to about 10%, we’ll do a second transplant.

We talked about where to do the second transplant if it’s needed.  UMinn is one of the three main Hurler’s centers in the country.  They’ve transplanted 113 kids and tracked outcomes for many more, they clearly have a wealth of experience to call on. Having said that, the transplant timeline can range from 2-6 months or even longer, and the prospect being that far away from family and support networks for that long is extremely daunting. 

It’s also true that UMinn has a full range of specialists from anesthesiologists to developmental and orthopedic specialists to work with patients. At the same time, we have a very good transplant hospital 20 minutes from our home.  When it comes right down to it, the transplant protocols are the same, and in the event that complications arise, the responses and interventions are the same. It’s true that the nursing staff and others at UMinn would be better attuned to working with the needs of Hurler’s kids as opposed to lukemia patients.  But overall the type and quality of care and the transplant outcomes aren’t significantly different and, in our situation and opinion, don’t merit the risks and difficulties of pursuing transplant so far from home. 

Sarah here: 
On the brain front, there is some really good news as well as a new challenge for us.  We met with several folks from the Neuro-Psych department at UMCH over the course of two days.  The first day Todd and I answered a lot of questions from one of their department about our perceptions of Ethan’s development and how he adapts to everyday situations.  Things like when did he first sit unassisted, crawl, and walk.  Also things like can he follow simple directions and how many words does he say or sign. (For those of you familiar with this field, we were completing the Vineland survey.)  During this entire time, Ethan and Caleb played in the room around us.  Caleb had his new dinosaur skeleton (a T-Rex) from the Minnesota Science Museum, so he was pretty occupied, and Ethan was Ethan—following his brother around, climbing on the chairs or our lap and babbling at us.

On Tuesday, Ethan and I walked back to the clinic and had a couple hours with two more folks—a graduate fellow and a grad student—who worked Ethan through the Mullen survey.  Lots of sorting shapes, pointing to objects to identify them and their uses, stringing beads on a shoelace, stacking blocks, pointing to pictures in books, kicking balls and going up and down stairs, and many other things to get a feel for his gross and fine motor skills, his cognitive development, and his receptive and expressive communication skills.  We took some diaper-changing breaks and a snack break, and Ethan was pretty tuckered out by the time we were done.  He pretty much fell asleep on my lap while the graduate fellow and Dr. Shapiro reviewed the results with me.

The fantastic news is that Ethan’s cognitive development is right on a par with a normal average to above-average 2 year old!  And his fine motor skills were average, which is a significant improvement from his score a year ago when he was tested for Early Intervention services.  He is somewhat delayed in his gross motor skills, which may be related to his orthopedic issues (the kyphosis and his knock knees and pronated feet.)  The real area of challenge is in his expressive communication.  Though Ethan makes himself fairly well understood by pointing and taking you to where he wants to go, that is starting to not be enough for him to express all he can understand.  Basically, his expressive abilities are falling way behind his thinking abilities.  Dr. Shapiro recommended that we immediately get him into speech and language services 2-3 times per week to help catch him up in his expressive communication, so we’re getting started setting that up.

This was so completely refreshing.  I think she is the first doctor who has said…this is what you need to do...go do it and do it now.  This is the difference there is between working with doctors who know their field and working with doctors who know Hurler’s patients in that field.  Dr. Shapiro has seen 50-80 Hurler’s patients, so she knows the effects of this specific disease in her realm of expertise and can say definitively…this is what you need to do.  What a revelation!  And a relief!

Todd again:
As you can see the neurocognitive testing that we had to fight for, turned out to be one of the most worthwhile and informative parts of the trip.  I had been wondering if we’d invested too much time and energy in fighting for that.  Receiving such positive and useful information from that testing reconfirmed for me that no issues are small or unimportant and that we need to keep fighting wherever we can for more and better access to services and information.

It was very helpful to see and work with some of the specialists at UMinn.  Through that we realized that while the transplant can be done here in Oregon, we will probably want to work with UMinn or another Hurler’s center for Ethan’s post transplant Hurler’s care.  Centers like UMinn, Cincinnati and Duke have experts a range of experts who specialize in Hurler’s issues, understand how treatment and disease progression has changed with the advent of enzyme replacement therapy, and understand and conduct the latest research and clinical trends.

For example, we’ve got one orthopedic surgeon that we we’ve worked with through Kaiser Permanente in Oregon.  At UMinn they have orthopedic specialists who work primarily with leg and mobility issues, specialists who work with arm and carpal tunnel issues and specialists who work with spine issues.  Similarly, as Sarah discussed, it was very helpful and informative to have neurocognitive specialists who can see through the hearing, vision and motor skills issues to accurately assess Ethan’s mental development. 

What that means for us, is that once Ethan is through transplant issues, we’ll likely start traveling to UMinn or another center for yearly evaluations.  The staff there will schedule a full range of examinations with all of the specialists he needs to see, and most of his surgeries would likely be done there.

For now, our health insurance benefit levels through Kaiser Permanente are so good, that we’ll stay with them until the transplant issues resolve.  Then we’ll likely switch to Blue Cross or another provider that will allow us to get treatment out of network without having to go through interminable appeals. 

It also means that we’ll likely be spending some time each year in another city getting medical treatment.  The amount of time will vary year by year depending on what surgeries he needs.  This is pretty common thing for MPS families. 

Finally, I wanted to add a note about the Ronald McDonald House where we stayed while we were there.

Before Ethan was diagnosed, I never knew what the Ronald McDonald House Charities were.  After his diagnosis, I started reading about families who stay at RMH while their kids are receiving out-patient treatment away from home.

Even though we were only in Minnesota for a few days, I wanted us to stay there so we could check it out in case we went back for transplant or future treatments.  I’m so glad we did.  I can not say enough about the facilities and services that RMH provides.  

The RMH Twin Cities house is a four building complex that can house 48 patients and their families.  The facility is set up to provide a comfortable, supportive home away from home for kids and their families who are working with life threatening illnesses.  Patient and family stays can range from a few days, as in our case, to 100 days or even a year. 

The house has comfortable rooms, 10+ fully equipped kitchens, play rooms and play grounds, game rooms, small and large living room and communal room nooks, exercise rooms and laundry rooms.  The staff and volunteers arrange all kinds of activities to help engage and support the kids and families.  At various points in the short time we were there, they set up a space for kids to have fun driving electric cars, had visits from therapy animals, had various community groups and volunteers come in and cook dinners for the residents, etc..

If you never knew what Ronald McDonald House Charities were about, please know that they provide a truly essential service for families in critical need.  So, the next time you or your kids are grabbing a burger at McD’s, be sure to drop a $20 in to the RMH collection box.

I suspect that we’ll be spending a fair amount of time at RMH in future visits.  It’s a wonderful relief knowing that such a great resource is there.

One last note, and a request for help.  Sarah and I would like to ask if there’s anyone in the area who can volunteer to take Ethan to one or two of his weekly speech therapy visits? Sarah and I are trying to save our sick and vacation leave in case we need to take significant time off to care for Ethan during a second transplant.  Sarah’s parents have been and continue to be a huge help with everything, but they have their own demands on their time and deserve some down time, too. 

If you think you might be able to pick Ethan up from daycare and drive him to and from his speech therapy visits occasionally, please let us know, it would be a huge help.