ERT and Transplant - Our Final Answer

To be completely honest, Gracie is at relatively low risk of having complications from the transplant. That said, how low can risk can one really be when fewer than 9 out of 10 kids survives the procedure?

Here is a list of contributors:

1. Prevention. When taking ERT, risks of pulmonary problems post-transplant are diminished. Taking a “risk averse” stance. This transplant procedure is risky enough. We want to remove as much risk as possible. Preventing pulmonary issues related to transplant. Most kids that experience serious problems experience bleeding in the lungs after being on a ventilator. Pulmonary issues, as referred to by the physicians. Most of those kids already have other pulmonary issues prior to transplant.

Gracie does not. And by taking ERT treatments, Gracie will not develop pulmonary problems (or other likely problems with tonsil and adenoids, etc), either before transplant or while waiting for the transplant to work (engraftment).

Dr. Tolar thinks that ERT “absolutely” benefits even healthier kids by protecting the lungs and other organs from GAG build-up.

2. Interim relief. As Kendra (Dr. Byoraker) relayed, “ERT is giving Gracie something that she needs, but doesn’t have.” The enzyme will help Gracie rid her body of the sugars that would otherwise accumulate throughout.

3. Both Kendra and Dr. Tolar expressed very directly how they would handle the situation if they were in our shoes. They would go forward with ERT. Although there isn’t sufficient data to prove that ERT will make a difference, Kendra and Dr. Tolar shared their beliefs in the treatment based on empirical evidence of the handful of babies and families that have gone through it. At the end of the day, ERT is a very low risk intervention.

Here are answers to questions that were leading to our reservations regarding ERT:

1. If Gracie takes the ERT, won’t that delay time to transplant? Yes, it probably will, but not by as much as we thought. The woman at Duke told us they can find a donor in 10 days. While technically true, she was only giving us part of the story. According to Dr. Tolar, there is a lot that must happen after the donor match is identified but before the transplant takes place. He said that it generally takes around 6 weeks, and they started last week for Gracie.

The research protocol calls for 12 weeks of ERT prior to transplant. To complete the protocol would mean delaying by 6 weeks at most. If we want to proceed with transplant as early as possible, we can always remove Gracie from the protocol once the donor cells are ready. There shouldn’t be a negative effect on her outcomes.

2. If Gracie takes the ERT, could that negatively impact the transplant, meaning lower engraftment rate or lower enzyme production rate once the donor cells take over? Dr. Tolar loved this question, and his answer is (emphatically) “no.” Again, the physician at Duke gave us pause when she warned us of the antibody reaction to ERT that happens in almost every child. Our worry was that this antibody reaction would influence transplant success. Dr. Tolar said that they had the same worry prior to offering combined treatment. They’ve tested and found that although there is an immune reaction and you will find antibodies, they don’t target the “active site” where the enzyme is produced (Mandy, there might be room for a biology cheat sheet on the active site).

Even though this question is at the root of why Duke doesn’t do ERT-combination therapy, Dr. Tolar said that the questions have been answered and are no longer relevant concerns. He said that there is no reason to worry about that.

Unfortunately, I left my notes in the stroller, which is still in the hospital, so I’m not 100% sure I am accurately recalling all of the important details that inform the emphatic no.

3. If Gracie takes the ERT, will that influence her chances of getting a severe case of graft versus host disease (GVHD)? Again, the answer is no. ERT has no positive or negative impact on GVHD.

I hope this is helpful and not overly complicated. This was a very spirited discussion that we had with Dr. Tolar and his team. They loved our questions and preparation, and genuinely are most concerned with helping us find the answers we needed to make a decision. I’m very confident that this is what is best for Gracie, and for our family. Thanks again for reading.