Days +136 to +138: Update

Thank you to all for your concern about Ezra. We really appreciate all the messages of support - they keep us going. After spending yesterday at the hospital with Ezra getting a full workup, it ends up that he has parainfluenza virus. This is a common virus that causes respiratory illness and cold-like symptoms in people with normal immune systems. In immune deficient patients, it can cause pneumonia, a very bad thing. Ezra's chest x-ray yesterday was thankfully clear and it better stay that way. 

His cough is worse, but not terrible. Ezra actually had parainfluenza virus after his first transplant and managed to recover well from it. Our only choice is to hope and believe that the same will happen this time. There is nothing that can be given to help him fight off the virus. We just have to remain vigilant for any signs of worsening symptoms.

We suspect that he picked up the virus from the hospital because he has not been anywhere else. No matter how many precautions we take, it seems these viruses still find their way to him. The hospital is the worst place for him and yet we have no choice but to bring him there twice a week until his cells are stronger.

Ezra's liver numbers have unfortunately increased. An ultrasound is scheduled for Friday. The doctor thinks that the elevated levels may be from the virus, but we will see what happens on Friday and go from there. We are praying there is nothing more sinister lurking inside.

On a positive note, Ezra never ceases to amaze us. He did so well with all the poking and prodding and manages to find the fun in everything. Whether it's an impromptu puppet show behind the lead vest in the x-ray room or making a game of jumping from square to square in the hallway, Ezra always makes the best out of crappy situations. He also lectured us last night about the Big Bang Theory, atoms and why Uranus rotates differently from other planets. It seems the more isolated he is, the more he wants to know about the universe beyond. 

Thank you for all the prayers and well wishes. Ezra continues to need them and we will continue to keep you updated.

Days +122 to +135: Dealing with the Costs and the Benefits

For the past two weeks, we have been dealing with some of the downsides of Ezra's post-transplant treatment. First, last week his hemoglobin dropped significantly in just three days. It ends up that he now has iron deficiency anemia. The doctors think that the tremendous amount of blood tests that are done twice a week combined with the two months post-transplant when he wasn't eating much have left his iron stores depleted. The plan is to cut back on the bloodwork a bit for now and to try to up his dietary intake of iron. If this plan doesn't work, he will receive iron by IV to boost his stores.

Then on Friday, his liver enzyme levels skyrocketed. They have been elevated since he has been on the steroids, but never this high. If the levels do not come down by Tuesday, then he will have a liver ultrasound at the end of the week. Hyper IgM patients are highly susceptible to liver disease. This combined with two transplants puts Ezra at high risk for liver problems, so this latest issue makes us shudder. It could be any number of things or it could be nothing. We are praying the results are just an anomaly and all will be back to "normal" this week. 

Ezra's white blood cell count and his lymphocyte counts (which include T cells) also dropped this week. They are at the lowest level they have been since he was discharged. The doctors are not too concerned yet. They think that it may, once again, have to do with the steroids, even though he is now at a low steroid dose, and his counts should be increasing instead of decreasing. All we can do for now is wait and hope things turn around soon. It is so hard watching his counts going in the wrong direction. 

On top of all this, Ezra has developed a mild cough. We're hoping it's just the dryness from the heat in this freezing weather, but everyone is watching this cough very closely. Much too much going on right now. Although, if you ask Ezra how he's feeling, he says "never been better." Hoping he knows something we don't.

The one positive that we are holding onto tightly is that he still has not required his IVIG treatment. His IgG level continues to fall, but slowly. He has now passed the 9 week mark since his last IVIG. This is our one sign that something in that little immune system is working. Right now, we will take any sign of a functioning immune system.

We want so badly to feel like Ezra is safe. Just as we thought things were starting to stabilize, these latest issues are a reminder that this journey is very long, and that there are more bumps on the road to good health for Ezra to overcome. 

Days +111 to +121: How Far We've Come

One year ago, we announced on this blog that Ezra's transplant had officially failed. We had just received the news that he had only 1% donor cells. Faced with dismal options, we wrote "It may be that the right decision is to not do anything. To let him be. To let him live. And to hope that someday soon that long sought after match appears." A few months later our hopes and prayers were answered when Ezra's donor appeared on the registry. After much anguish, we decided that it was not better to let him be and that a chance at a cure was better than life with a sword hanging over his head. And now here we are one year later. The verdict on this transplant is still out, but things are moving in the right direction and so far we are in a much better place than last year at this time. There is much to be grateful for.

The latest round of testing on his T cells is back. There are multiple types of T cells. The type of T cell that he had a small amount of last month is down slightly, but basically the same, which is likely due to the steroids. The good news is that a small amount of another type of T cell has appeared! One step back, one step forward. 

There's been another good sign: Ezra has been able to go longer in between infusions of his immunoglobulin replacement therapy (IVIG). This is the treatment that Ezra has received every four weeks since he was diagnosed. It is what has kept him alive for the past four years. Ezra does not make an immunoglobulin called IgG, or at least he didn't before this second transplant. This was the level that came back drastically low when Ezra was sick with pneumonia at four months old and our first indication that there was something terribly wrong with his immune system. Each week, his levels of IgG are checked to see if he needs the treatment. The level has been dropping, but more slowly than his usual rate. He is now more than 7 weeks without IVIG, the longest he has gone without it. He may need it soon, but the doctors tell us that the fact that he is holding longer means that maybe, just maybe his body is starting to make IgG and his new immune system may be starting to function.

Ezra remains on a low dose of steroids. The wean is going very slowly. Thankfully, there is still no sign of the rash.

Ezra was loving the snowfalls of last week. He had been waiting for the first good snow basically since we got home from the hospital. He ran around yelling "snow angel!" and dropping backward into the snow. Seeing the snowflakes glittering on his newly re-grown eyelashes was a breathtaking sight. A little snow angel indeed.

Happy Holidays!

Days +103 to +110: Good News!

Today brought fantastic news: Ezra's T cells are 99% donor!!! And all other cell lines are 100%! We are beyond relieved and so thrilled! The news comes after we had a stressful discussion yesterday with Ezra's doctor where he was preparing us for the possibility that his T cells will be mixed chimerism. With T cell depletion transplants, it is apparently not unusual for the T cells to grow back mixed initially, and then the donor cells take over as time passes. This would have been a difficult scenario for us to handle given what happened with Ezra's first transplant. We knew that mixed chimerism was a possibility from the beginning and that his cruddy T cells are not so easy to knock out, but we were praying that we would never have to see those defective T cells again. Based on these results, it looks like Ezra's CD40 Ligand deficient T cells have hit the road. Adios T cells - you will not be missed!

We are hoping that Ezra's incredible-needle-in-a-haystack-miracle donor feels our joy and gratitude wherever she may be. This is all because of her. We welcome all of her cells and love them and her fiercely.

Ezra, by the way, does not know about any of this. We learned our lesson the hard way with the first failed transplant that we should not tell him much about his new cells until there is more certainty. Until the GVHD stays away and until he has the necessary amount of functioning T cells, we will not give him details. All we tell him is that his counts are good, he is doing great, and that we are so very proud of him. We patiently look forward to the day when we can tell him he has a new, strong immune system and he can go conquer the world. For now, we keep our victory dances for when he is sleeping.

The next steroid wean started last night. He will be on the steroids for about another month at the current rate. The rash has not returned. With these lower doses of steroids, it is more likely that the GVHD may flare up, so we are watching his skin very closely. The amount of T cells will likely be checked again at the end of the week. We are not expecting much T cell growth, if any, due to the steroids.

Thank you to everyone for sharing Ezra's YouTube rocket video! He has over 2,200 views and he is thrilled! He loved hearing all of the awesome comments! Thank you for giving him something to look forward to and to enjoy!

Days +91 to +102: Adventures in Steroid Land

Life with Ezra on steroids has been interesting. First, the good news is that the rash has not re-appeared. We have been able to reduce the steroid dose twice, and will be starting a third reduction. The rate of the wean starts to slow down now, so Ezra will be on steroids for at least another month, depending on how things go. It is frustrating because the steroids suppress T cell growth, but we will do whatever gives him the best chance of overcoming the GVHD.

Despite the reductions in steroid dose, Ezra is still dealing with the side effects. The steroids have caused his appetite to increase, which right now is a good thing because he is still regaining the weight he lost during transplant. The problem is that his appetite is mainly for chips. Steroids effect the salt-water balance in the body and can cause bloating and an increase in blood pressure (and blood sugar and many other bad things), so the doctors want us to watch his sodium intake. We have now gone from desperately wanting Ezra to eat and encouraging him to eat whatever he wants as long as he eats, to gently pulling back on the one food he wants more than anything else. Poor little dude must think we are crazy. He also has been experiencing the drastic highs and lows from the steroids. He goes from hyperactive to completely exhausted. Ezra is not a hyper child, so the last two weeks have been interesting. We are hoping that as we go down on the steroid dose, the side effects will subside.

Ezra has reached the Day 100 milestone. Day 100 is often touted as a marker of survival. Studies show that patients reaching day 100 post-transplant are more likely to survive in the long run. In Ezra's case with the type of transplant he had, Day 100 isn't all that significant. The more important milestone will be when he has a strong number of functioning T cells and is able to be free of the steroids without GVHD re-appearing. That will be cause to celebrate.

Ezra has been basking in the light of Hanukkah. Candles, songs, a gigantic menorah, and presents - what's not to love about Hanukkah when you're four years old? This year, the unspeakable thoughts that have tainted every joyous moment since Ezra was diagnosed seem to be a bit more subdued. Ezra's health is still in a very precarious state with so much of the path ahead unknown, but the progress he has made so far is huge. So, maybe day 100 is indeed a moment for feeling a little triumphant in the long fight for a cure. 

Happy Hanukkah! Love, Robin, Evan and Ezra

P. S. Ezra wanted to make a YouTube video of one of his model rocket launches "for other little kids." He likes asking how many views his video is getting, so if you have a few minutes, check out his video at 
http://youtu.be/_XFjETWPmus

Thanks!

Days +87 to +90: The Silver Lining

If every cloud has a silver lining, then we found the silver lining of Ezra's GVHD. He now has a very small number of T cells. Although the T cells are causing the GVHD, if we can get it under control, then having T cells is exactly where we want to be. The steroids prevent T cells from growing, so the sooner Ezra is off the steroids, the better. Once he is off the steroids, the expectation is that the T cells will continue to grow and Ezra will be on his way to a functioning immune system. IF he can get off the steroids.

We have thankfully started to wean the steroids. The rash is completely gone. The dose has been cut in half and will remain that way for a week. If there is no sign of GVHD, we will cut the dose again and go from there. If the rash comes back, he will go back on the higher dose. We are anxiously watching and trying not to obsessively check his skin.

The other piece of good news is that the higher level chimerism test showed that all cell lines that Ezra has (not including T cells) are 100% donor. Yes, it is still possible that Ezra's T cells can end up being mixed chimerism, despite the fact that all other cell lines are 100% donor. T cell chimerism will be checked once he has more T cells.

The wean couldn't come soon enough. The steroids are wrecking havoc on Ezra's stomach. We are already seeing improvement in how he feels since cutting the dose. We've been struggling to figure out ways to help Ezra deal with his pain. Fortunately, Ezra has figured out his own way to deal with the pain - with "pain rockets." He pretends that one of his rockets is a pain rocket and he launches it into space where it hits an asteroid and all the pain disappears into space where it can never hurt anyone again. It's working for him, at least for now. 

The super-sized menorah is back on our front lawn ready to light up our Hanukkah! For those of you who have noticed compared to last year's picture, yes, he is most definitely taller! Here's to hoping that the holiday of miracles brings the miracle of no GVHD and a growing immune system.

Days +83 to +86: GVHD

On Thursday, after looking at a picture of Ezra's rash, the doctor decided that it is indeed what we have feared - Graft Versus Host Disease. The rash had not spread, but the rash on his back was worse. She also decided that it was best to be aggressive with treating it and started Ezra on "systemic" (oral) steroids, rather than waiting and trying different topical creams to see if they would lessen the rash. Steroids are a major problem post-transplant because they suppress the number and replication of T cells, delaying immune reconstitution. This is the last thing Ezra needs at this stage when we are anxiously awaiting the appearance of T cells. Steroids are a game changer. They also can cause very serious side effects. But the doctor explained that they have found that if you wait too long to treat GVHD, it becomes much harder to remedy, and it is best to attack it early.

Since starting the transplant process, GVHD has been our greatest fear, short of Ezra dying. This latest set back is very difficult for us to come to terms with. We were told that a T cell depleted transplant (the type of transplant Ezra had) has a 5-10% risk of GVHD. For his first transplant, we were told there was about a 10% chance of engraftment failure. Why our one-in-a-million son ends up on the wrong side of the statistics so often is a question to which we will never know the answer. And yet, we know we are lucky that he has so far landed on the right side of the most important statistic - he is alive and he is fighting.

The good news is that the rash responded immediately to the steroids - it was much improved after just the first dose. The plan is to stay on the higher dose of steroids for a few more days at least and then start a slow wean. The concern is that the GVHD will flare up once the steroids are weaned and that will require an indefinite course of steroids, and result in continuing impact on his immune system and other organs. We will all be watching closely once he is allowed to start the wean.

The confusing part of this GVHD flare up is that as of a few weeks ago, Ezra had no T cells. T cells are what causes GVHD. The new T cells that form from the stem cells from the donor and "grow up" in Ezra are not supposed to cause GVHD. It is typically T cells that come in with the graft at the time of transplant that cause GVHD. With the T cell depleted transplant that Ezra had, only a very small number of T cells come in with the stem cells. Ezra received even less than the level of T cells that Sloan considers "safe" - so small an amount that T cells have been undetectable since the day of transplant. 

So, how does Ezra have GVHD? Well, first of all, labs were drawn on Friday to check again for T cells. If there are T cells, there is no way of knowing if they are the very small number of donor T cells that have multiplied for some reason or new T cells that aren't behaving as expected and are attacking Ezra's skin. If the test comes back showing no T cells, then the assumption is that there are T cells in his skin and organs, but not in his bloodstream, which is why they have been undetectable. His doctor has described GVHD as a "black box" in many respects, and that has been our impression of so much of the transplant process. It is, and always has been, an enormous leap of faith.

Just as we had finally gotten the real Ezra back, we now have yet another version of Ezra - steroid Ezra. Steroids can cause stomach upset and Ezra's weakened stomach is already causing him more pain.  It is so frustrating to go backwards after he had made great strides. 

Please send prayers and positive thoughts that the T cells chill out and leave Ezra's skin alone ASAP (Ezra Aviel ben Hertzelia Shandel). And please wish us all courage as we confront one of our greatest fears.