THE CURE

The news we have been waiting for, praying for, and fighting for has arrived. Ezra has responded to the vaccine. His immune system did what it was incapable of doing prior to transplant - he made antibodies to protect himself from infection. And it is a real, good response. For once, we have test results that aren't "so-so" or "unclear." He made a beautiful antibody response, and there's no doubt about it. This is the cure.

Ezra's immune system is in a good place. What is left to be seen is the terrifying part - how he will do in reality, rather than in the Petri dish, when faced with an infection? The other issue is that as long as he has a port in place, he is on a fever "alert" where we must bring him into Sloan at any hour if he develops even a low grade fever. Anyone who has a port or a line is at risk of a very serious blood infection. All fevers must be taken seriously and IV antibiotics administered immediately. Initially, he will also need to come to Sloan for any illness to check his counts, etc. If he does well, with time, those visits should be relaxed.

The other remaining issue is that he is still on a low dose of steroids that need to be weaned and we need to make sure he has no auto-antibody flare up as he is weaned. So for now, we continue with regular clinic visits.

At the end of the visit as we were getting ready to leave, Ezra's doctor told him that he doesn't need to wear his mask anymore. At first he just shrugged his shoulders in a "whatever" way. But when he went to step into the hallway, a huge smile spread across his face, and then he had to tell everyone we passed that he wasn't wearing a mask.

We have to step back and marvel with appreciation that a cure for Ezra's disease was even possible. There have been no protocols and very little experience to guide Ezra's doctors on the best approach for transplanting him - a situation made more complex by his first failed transplant, the degree of mismatch of his donor and then the rare complications he suffered. But his doctors did it. Some of you may recall that Ezra's primary transplant doctor suddenly and sadly passed away shortly before Ezra's second transplant. The entire transplant team embraced Ezra, but one attending took a particular interest in Ezra and became his primary transplant doctor. We are forever grateful to Dr. Susan Prockop who takes devotion to her patients to another level and has been a source of brilliance and guidance through this journey.

We are bursting with gratitude for Ezra's donor - his "special lady," as Ezra calls her. At the one year post-transplant mark, we were permitted to exchange contact information with Ezra's donor. We eagerly filled out the paperwork, but the donor registry has not heard back from the donor. We are not given any further information and do not know if she has changed her contact information or if she just does not want to respond. We have sent her anonymous letters and have told her that whenever she is ready to be in touch, we will welcome her with open arms. It will always feel like there is a hole in our lives without the special lady who we searched for so desperately and who so unselfishly saved our son's life. We will think of her always and hope she knows what a hero she is to a little boy and his family.

It has taken a village to cure our son. From his donor, to the blood and platelet donors who flooded the MSK donor room, to the delicious meals that appeared on a daily basis, to the gifts for Ezra, to the messages, emails, and calls, we have been overwhelmed by the support and love. This journey would have been impossible without all of you.

Now starts what we are considering to be Phase Two of Ezra's recovery: socialization and independence. Ezra has had minimal contact with other children and has never been separated from a caregiver. We are going to go very slowly and carefully with this phase as we did with the medical phase.

This past Sunday we celebrated Ezra's 6th birthday. It was a day of great joy, especially when compared to his 5th birthday, which was spent in the hospital and was one of the worst days of our lives. For the first time, the fear that has overshadowed each of his birthdays has quieted, and we dare to look ahead to a long lifetime of birthdays.

This journey is not quite over. Rather, we are beginning a new, wonderful phase.  We will continue to post updates of hopefully more milestones reached and surpassed.

In the beginning of our journey to cure Ezra, one of the world's experts on Hyper IgM, in recommending that Ezra be transplanted, said to us "do you want him to live with a sword over his head?" This question has always haunted us through this journey, and in particular, has echoed through our heads as we struggled with gut wrenching medical decisions. That ever-present sword has just been thrown to the side. Now all we see above Ezra's head is a sparkling world of potential, adventure, laughter and love.

One Part of the Cure

We happily received some good news this week. The specific type of Hyper IgM Syndrome that Ezra has is called X-linked CD40 Ligand Deficiency. CD40 Ligand is a little protein found on the surface of T cells. It is responsible for communicating with B cells and instructing the B cells to make antibodies, as well as signaling other cells of the immune system to take action when an infection is detected. Ezra had a "complete absence" of CD40 Ligand on his T cells when he was diagnosed. Some patients with CD40 Ligand Deficiency have CD40 Ligand present on their cells, but it doesn't function properly. Some doctors believe that the absence of CD40 Ligand as in Ezra's case is a more "severe" form of the disease. A little protein that causes a big mess of you don't have it. 

We tested Ezra's CD40 Ligand for the first time since his second transplant. We have the results from the first part of the test, which looks at whether the T cells have CD40 Ligand and whether it increases when stimulated. Ezra now has CD40 Ligand on his T cells! The numbers are below normal, but not too bad. His doctor thinks his immune system needs more time to fully mature, but she does think that the current level is protective - provided the CD40 Ligand functions properly. 

The second part of the test, which measures the function of the CD40 Ligand, is not back yet. We hope to have the results in the next few weeks. The function may not fully be there because unfortunately, Ezra's IgG decreased again last month and is pretty low. It isn't so helpful to have CD40 Ligand and for it to not function. But first things first - you have to have it for it to function. Ezra now has CD40 Ligand and that's a beautiful thing. 

This good news came on the one year anniversary of when Ezra developed the very harmful auto-antibodies, the ramifications of which he is still dealing. Looking at the lab report brought us back to September 2009, when Ezra's usually cheerful pediatrician suddenly was not so cheerful as she handed me the results of this same test. I comprehended only a few words from the cover letter from the lab - a diagnosis of Hyper IgM and a referral for transplant. The rest blurred together in a fog of devastation. Then I looked at my smiling baby boy, and that was the moment when I knew that Ezra would no longer see our tears or anguish. He would know as much joy as we could provide, and we would carry him through the unavoidable suffering with laughter and love. 

One part of the cure is checked off the list. We have no idea if he will pass the function test, and it still remains to be seen if he can make antibodies in response to a vaccine, which needs to happen to know he is safe. Next week, Ezra unbelievably turns 6 years old, which also means we've been fighting Hyper IgM for 5 years and 8 months. At this point, we are just happy to know that there is some forward movement and that Ezra's new immune system is still a work in progress. 

Third Time's A Charm?

Ezra received another vaccine shot on Friday. Now that he is on a lower dose of the immune suppressant, his doctor thought it was a good time to try and vaccinate him again. They will probably test for an antibody response at the four week mark, but his doctor said it is more likely to see a response at the eight week mark. IF we are to see a response. 

Ezra handled the shot so well - much better than last time when we had no advance notice. It is really incredible to watch him draw on all the strategies and methods he has learned over the years of medical trauma to pull himself through to a place of calm. We are very proud of him. 

Unfortunately, Ezra's IgG level (IgG level is basically the amount antibodies circulating in your blood at any time ready to fight off infection and the type of immunoglobulin that Ezra could not make prior to transplant) has decreased again. It has not dropped by a huge amount, but it also is not increasing. His doctor thinks his body is making some IgG, but not enough. Once again, what is most important for everyone to see is if he can respond to a vaccine. They are not going to give IVIG at this point, unless he gets sick or his IgG level drops more severely. 

With the lower IgG level, we are not sure that Ezra's going to be able to respond to the vaccine. We remain ever hopeful. They also took a slew of labs to check on Ezra's immune system and to make sure nothing is getting out of control on the autoantibody front now that he is on lower doses of steroids and the immune suppressant. More labs will be sent at our next clinic visit as well. It will be a nerve racking month for us as we wait for all these results to come in.  

While the country is in the midst of a measles outbreak and the ensuing debate over vaccination, it feels somewhat ironic to sit here praying for Ezra's immune system to have the ability to kick into action and respond to this vaccine. The people who choose not to vaccinate their children do not even realize how lucky they are to have a choice whether to vaccinate (and it should not be a choice). Anyone who has been following Ezra's journey knows what we would give for Ezra to be capable of making antibodies. It takes just a few minutes of learning about the immune system and these devastating diseases to see that vaccination is a gift. 

We have no choice. All we can do is to hope and pray that someday soon Ezra's new immune system starts to properly function. In the meantime, we are forced to rely on others doing their part at keeping deadly disease out of our communities. 

Unfortunately, we fear that too many do not care about the plight of their immune compromised and medically fragile neighbors, as well as all the children too young to be fully vaccinated. We shouldn't have to fear that others will make a "personal" choice that may threaten our son's life. Too many choose self over the health of the community, and not just in the realm of vaccination. We are left cringing at every report of an additional case of measles. An unnecessary fear to add to our list of fears. 

Please join us in hoping and praying that the third try does the trick and Ezra's immune system properly responds. And that we can keep him safe while we continue to wait. We will keep you all posted. 

Patience

The past two weeks have been great fun for Ezra, and he has enjoyed the holidays and the new year celebrations. We don't have the best news to report on the medical front, unfortunately. We got the results back on the vaccine antibodies. Unfortunately, Ezra has not responded to the vaccines. It does look like he has responded to polio, one of several vaccines he received, but the doctor wants to see him mount more of an antibody response before we breathe any sigh of relief or make any changes to his treatment/situation. There is no real explanation for why he responded to one vaccine and not the others. The plan is to give him another shot in a month and see if he responds then. 

We are of course disappointed and worried that he did not respond to the vaccines. Ezra's doctor, while also disappointed, is confident that with time and lower doses of the immune suppressing drugs, he will be able to have a proper antibody response. Bottom line is that we continue to need to be patient. We've been patiently waiting for a cure for the past five years, and we can certainly stay the course. We always say that as long as things don't go in the wrong direction, we can be as patient as can be. 

In the meantime, he needs to get onto a lower dose of the immune suppressant to have proper immune system function. The dose has been going down by very small increments each week. So far, so good. His counts are not showing any signs of autoantibodies. The only other lingering issue at the moment is his iron levels, which are dipping again. At least that issue is easily remedied with IV iron, as long as we keep a close eye on the levels. 

We are prepared to hunker down for the germy winter. Our number one goal, as always, is to keep Ezra safe, healthy and happy, and hope that his immune system gets its act together soon. If we don't blog as often, please don't worry - it means that all is status quo, at least for the most part. Here's to hoping for some quiet times as we start 2015!

P.S. For those of you who do not follow Ezra's Facebook page, here is the link to an article I wrote about Ezra and the Gift of Life Bone Marrow Foundation for the New York Times parenting blog: http://nyti.ms/1ztEpys

T It Up!

Good news on the T cell front - Ezra's T cells have reached the normal range! We also received the results of the general function T cell test and his T cells have surpassed the "two-thirds of normal" immunological marker. They aren't functioning normally yet, but they are making slow and steady progress towards a safer place. Looking back to September, Ezra still had very few T cells, and it felt like we would never see the day when he would have normal T cell numbers. Now, three months later, he made it!

Although we have reached this milestone, nothing changes as far as his treatment and isolation. In fact, Ezra had normal levels for these tests prior to transplant, but this is an important milestone for a post-T cell depleted transplant patient. We still need to see if he can make antibodies in response to the vaccine. This will be the true test of whether he is cured. Another round of tests to see if he responded to the vaccine have been sent to the lab, and we should have the results in the next couple of weeks. Please send some positive antibody thoughts Ezra's way!

We have also continued the slow wean of the immune suppressant. Getting off the immune suppressant and steroids is another challenge that Ezra needs to surmount in order to have a properly functioning immune system. His doctors are keeping a close eye on his counts to make sure there is no autoantibody flare up while we wean. So far, so good. 

We have been fully enjoying the light of Hanukkah this year. It isn't just the giant menorah that is once again on our front lawn. It is the love that has been bestowed upon Ezra. He has received gifts from many people who we know wish him good health most of all, but want him to also enjoy himself in the meantime. He is having a blast! 

We also had the opportunity to celebrate the holidays at Menorial Sloan-Kettering's annual pediatric holiday party. We spent time with Ezra's wonderful primary nurses from his time in-patient and celebrated with the doctors, nurses and staff who have gotten us through the most difficult times of our lives. It is also Ezra's favorite time of the year at the hospital because hidden away in the basement level is a magical hallway transformed into a winter wonderland by the operations staff, including a model train display that always captivates Ezra. We've become experts at finding light in even the darkest of places. Happy Holidays to all!

Living In Limbo, But It's Ok

We had a chance to speak with Ezra's primary transplant doctor this week at clinic about the state of Ezra's immune system. As we wrote in the last blog post, we have been feeling very unsettled by the fact that the part of Ezra's immune system that isn't working right now (the ability to make antibodies) is exactly the main part that wasn't working prior to transplant. We got back the results on the vaccine antibodies test from a couple of weeks ago. He may have responded to the polio part of the vaccine, but for complicated reasons, the results are not clear. He definitely did not yet respond to the other viruses/bacteria in the vaccine. Ezra's doctor believes it is too soon. They will check again in two weeks. 

If he still has not responded, Ezra's doctor assured us that she does not think that it is because of Hyper IgM Syndrome. She said that the communication between the T cells and B cells that is needed for B cells to make antibodies (and what Ezra's immune system was not able to do prior to transplant) is the last function to come back post-transplant, especially in T cell depleted transplants. She is optimistic that if we can get him off the immune suppressant, then with time the ability to make antibodies will come. His IgG also stayed the same for the past two weeks. It would be reassuring to all if we can see an increase in IgG, but we will certainly take stability - and it buys us another two weeks without IVIG. 

Ezra's doctor also explained that Ezra is in a safer place in terms of handling an infection now that he has more T cells and their function is improving. They are most concerned when there are low numbers of T cells and they aren't functioning. We obviously don't want to test this out, but it was very good to hear that he is making progress. Another T cell check is cooking in the lab and we should have the results in a couple of weeks. 

Thankfully, we have started weaning the immune suppressant. The wean will be slow over several months. He is still on a very low dose of steroids and we will hold him on this dose for now while we wean the immune suppressant. We are praying that he doesn't have an auto antibody flare up while we are weaning. 

Despite all the uncertainty, we are starting to feel like there are slivers of hope for the future. For the first time, I bought a shirt for Ezra during the holiday sales to put away for next year. I had never before allowed myself to buy something in advance for him. It always seemed presumptuous to think there would be a next year. Throughout this journey we've learned the hard way to never think ahead and to take each day at a time. We are starting to allow ourselves little glimmers of a healthy future, and we so hope we aren't proved wrong. 

Trying To Be "Cautiously Optimistic"

The last few weeks have been spent trying to assess the state of Ezra's immune system, but after all the testing, we are still left in a state of uncertainty. We always try to focus on the positive and there is much to be grateful for at this point. Ezra is now on a very low dose of steroids and there has been no sign of the auto-antibodies. We have not yet started to wean the immune suppressant. We are hoping that will happen at some point next month. 

With the decrease in steroids, Ezra's new T cells have started functioning. To assess T cell function, Ezra's doctors run a test to see how the T cells respond to a "general" stimulant (as opposed to a virus or bacteria). Studies have shown that patients can fight off certain infections that are a concern following a T cell depleted transplant with two-thirds of normal function. Ezra's T cells are inching closer to that "two-thirds of normal" milestone. Ezra's T cells performed normally on this test prior to transplant. So not so exciting in terms of a cure, but a very good indicator in terms of T cell recovery post-T cell depleted transplant. 

They also performed another T cell function test relating to the vaccine Ezra received. His T cells were able to respond to one of the strains of bacteria in the vaccine. Ezra's T cells were NOT able to respond to this same bacteria after we attempted to vaccinate him prior to transplant. This is at least some change in his immune function, which we were very happy to see. Based on this result, Ezra's doctor said that she is "cautiously optimistic."

BUT (there's always a "but"), Ezra's IgG levels have dropped. Between his failure to respond to the first round of the vaccine and dropping IgG levels, his immune system is acting just like it did prior to transplant. The doctor decided to test to see if he has made any antibodies in response to the vaccine even though it is likely too soon from the second shot to see a response. If he shows some response at this point, it will be a miracle. Most likely, it is too soon. Or he isn't going to respond at all because of the immune suppressant and his newly rebuilding immune system. We can't help but fear that this part of his system may not come back at all. As much as his doctors believe it will, after all we have been through, we will believe it if and when we see it. 

The tricky issue is whether he needs to get a round of IVIG. We are all concerned about protecting him during the germy season. The problem with giving him IVIG right now is that we lose the opportunity to see if he has responded to the second round of the vaccine because it will be impossible to tell if he responded when he is getting the antibodies from IVIG. The other issue with giving him IVIG is that it will be another 4-6 months before we will know whether he is able to make IgG and antibodies on his own. That means another 6 months at the least of isolation and uncertainty. The older Ezra gets, the more concerned we are about his lack of contact with other children, and another 6 months of isolation is definitely not what we want. We will wait for the vaccine results to come back and go from there. 

As we enter this week of thanks, we are very grateful for how far Ezra has come. Looking back to last Thanksgiving, Ezra had recently developed GVHD, was on high dose steroids, and we were very frightened of the course the GVHD might take. He has overcome many obstacles, and we know more challenges lie ahead. Right now, he is feeling well and is a very happy little guy. And for that, we are more than grateful.