Tuesday, May 25, 2010


Transplant Day +209

We received the results of Ethan's 5/17 chimerism test yesterday, and the news is not encouraging.  The percentage of donor cells overall has decreased again, including the marker that indicates the stability of the transplant.  While it is still possible that the transplant may stabilize, we are beginning the search for another bone marrow donor in case a second transplant becomes necessary.

The numbers aren't changing dramatically, but they are dropping fairly consistently.  At the moment, Ethan is still in that grey area, where his body seems to be producing enough enzyme to protect his neurological development, but he needs supplemental enzyme infusions to control physical symptoms and protect his internal organs and skeletal development.  However, if his chimerisms continue to drop, that will change and his body will stop producing enough enzyme.

In a conversation with Ethan's doctor, yesterday, she said that she wasn't optimistic that the transplanted graft would stabilize.  She said that it may still stabilize, but that given the consistency of the decline, she wanted to be ready to do a second transplant if we need to and was going to start the search for a new bone marrow donor.
While we received the chimerism results yesterday, we’re still waiting for results on his enzyme blood level and the amount of mucopolysaccarides in his urine.  Those results will tell us how much enzyme his body is producing now and the urine test will give some indication how much mucopolysaccaride waste is building up in his system. We’ll see what those results tell us and then will do another chimerism test in June and see what that tells us.
(For those who are interested, I’ve listed some of Ethan's test results to date at the end of this journal entry.)
Once we have the June test results, I think it’s likely that the four of us will go to the Hurler’s center at the University of Minnesota to discuss Ethan’s case and to explore either the question of long-term enzyme replacement or a second transplant. 
In addition to concerns about the transplant itself, we’re also starting to see some dangerous side effects of the medications that Ethan’s been on for so long.
The doctor’s have been using immosuppresent drugs, cyclosporine and mycrophenolate mofetil, to suppress certain parts of Ethan’s native immune response to allow the donor cells to engraft.  However, Ethan’s been on these drugs for so long now that we’re starting to have to deal with negative side effects.  Ethan’s been receiving nighttime IV fluids for months to help push more fluid through his kidneys to protect them against damage from the drugs.  Over the last month, we’ve also been seeing potentially dangerous levels of potassium in his blood. High levels of potassium can trigger cardiac arrest, so they’ve been giving him a particularly horrible looking medication called Kayexalate (sodium polystyrene sulfonate) to control it.  He’s got to take 52ml of this stuff.  He doesn’t like it and I can’t blame him a bit!
Last week, in light of the side effects Ethan’s having, they had us start to taper Ethan’s immunosuppressants with a goal of having him off of them by October.  This week, after receiving the latest chimerism results, they had us go back up to the full, therapeutic, dose, but took him off of cyclosporine and replaced it with Tacrolimius in an effort to reduce his potassium levels. They also want to see him again this Thursday for blood work. 
Outside of all of the medical stuff that’s going on, Ethan is still the same happy, outgoing kid that we know and love.  If anything, he’s become more expressive and outgoing over the last few months.  He still doesn’t talk much beyond “mama” and “ba” (dad), “dat” (that) and a few other word approximations. But he hears and understands quite a bit of what you say, and will do what you ask, or nod or shake his head.  He’s also started tapping people when he wants their attention.  He’ll come up and tap you on the leg or arm until you give him your attention and he can tell or show you what he wants to.
Ethan started back to daycare part-time in the middle of May and he’s settling in really well.  We started him off one class lower (by age) than he should be.  But that’s okay, because the adult to kid ratio is a bit better and he can settle into the routine, and we’ll probably move him up in the next month or so.  He’s doing well enough that we think we can move him into full-time day care in June so that Grandma Pat and Grandpa Bob can get some much needed rest.  Who knows maybe they’ll even take a few days and go to the coast or Seattle or something (hint, hint).  Ethan’s return to f/t daycare will also allow Sarah and I to stop telecommuting aside from Ethan’s enzyme treatments and checkups.
Caleb is doing really well, too.  He’s a wonderful five year old. He’s into dinosaurs and snakes and rocks and mud puddles.  He’s always a great big brother to Ethan (unless Ethan’s got his toys).  Caleb’s also a great artist in training.  He’s really taken to coloring, whether in coloring books or freehand.  He’s both creative and methodical, to the point where he tests the color of a crayon on the back of the page to make sure it’s just the shade that he’s looking for.   Caleb also went to his kindergarten orientation last week, so Sarah and I, at least, are excited about this upcoming milestone!  As you would expect, Caleb is both excited and scared.
So, at the moment, we’re all still taking it one day at a time. 
Thanks for checking in on us. 
-Todd
Test Results
Chimerisms
There are four genetic markers that they track in monitoring Ethan’s transplant.  Unfortunately, I can’t add tables in the journal, but here’s how they’ve tracked.  Numbers below are % donor cells.
CD3 (T-Cells) 11/25    88%
1/20       80
2/17       79
3/15       68
4/19       48
5/17       37

CD19 (B-Cells)
11/25     99%
1/20       93
2/17       84
3/15       77
4/19       88
5/17       89%

CD33 (myeloid)
11/25     95%
1/20       57
2/17       54
3/15       37
4/19       34
5/17       29

CD56 (NK Cells)
11/25     100%
1/20       93
2/17       80
3/15       72
4/19       73
5/17       64          
The CD3 and the CD19 markers, above, are the ones that are responsible for making the enzyme that Ethan’s missing.  As you can see they’re split, one’s at 37% and one’s at 89%.   Ethan’s last iduronidase level was 37%, so clearly it’s not as simple as taking an average of the two to determine the level, I’m not sure exactly how it works.
The CD33 and CD56 are the markers that indicate the stability of the bone marrow graft.  The doctors look at the CD33 marker in particular and are not happy that it’s been declining steadily and is now at 29%.  As I understand it, if that marker gets to around 10%, they will consider the transplant to have officially failed.

Mucopolysaccaride Waste (Urine test)
Normal Rnage: <30.0 mg/g
7/8/09                   406
12/3/09                58.7
4/5/10                   66.2

% Iduronidase blood levels (Ref. Range) 100-120%
Enzyme that Ethan’s body is producing
7/15/09                0
1/25/10                43
3/29/10                37

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