Today was the day that Stephanie and Kolt met with Dr. Flake in order to review the test results from the transplant. It has been a stressful week full of anticipation, excitement, nervousness, and reservation. We knew going into this process that nothing was guaranteed, and that there were a few potential options that ranged from complete cure, to partial engraftment, to no change at all. After meeting with Dr. Flake, we were able to discuss the results and our options.
- The best outcome is all goes well, the baby takes the stem cells, creates a functioning immune system, and life is back to normal.
- There is a chance that the baby only takes a portion of the stem cells, and not enough to completely replace the defective genes. This is still a good sign, as it makes future procedures much more tolerable, such as the bone marrow transplant. This would mean lower dosage with chemo, perfect immunological match with Stephanie, etc.
- There is a chance that the baby does not take any of the stem cells, and is born as if nothing ever happened.
- There is a very small chance that something goes wrong in the procedure and the baby is lost.
As this picture clearly demonstrates, option number 4 (loss of the baby from the procedure) did not happen, and Kolt has been going through the traditional newborn steps of breastfeeding, growing, and becoming more familiar with his surroundings. Over the past week, once he and Stephanie were discharged from the hospital, they even felt up for making a day trip to Atlantic City, and the Jersey Shore. Not too shabby for a newborn and woman that just had a baby. (But they eat gluten free, and take supplements, so anything is possible…)
When it comes to the results from the transplant though, we did not get the results that we were looking for. Even though Kolt appears to be healthy in every way, the specific tests associated with the transplant do not appear to have shown a reversal in the Hyper IgM diagnosis. That is to say, there appears to be no engraftment from the stem cell transplant that we did while he was still a fetus. The whole blood engraftment numbers are at 0%.
Interestingly, there is about a 2% reading of donor T-cells in Kolt’s blood, which higher than expected in infants. Generally speaking, infants are born with trace amounts of donor T-cells from the mom, and they have their own as well (these are the part of your immune system that kill things). Once again, with Hyper-IgM Syndrome results from a defect or deficiency of a protein that is found on the surface of activated T-cells. The affected protein is called CD40 ligand because it binds, or ligates, to a protein on B-Cells called CD40. The CD40 ligand is made by a gene on the X-chromosome. Therefore, this primary immunodeficiency disease is inherited as an X-linked recessive trait, which is why women are carriers, but men present with the condition.
As a consequence of the deficiency in CD40 ligand, the T-Cells in patients with X-linked Hyper IgM (XHIGM) are unable to instruct B-lymphocytes to switch their production of immunoglobulins from IgM to IgG, IgA and IgE. CD40 ligand is also important for other functions carried out by T-lymphocytes, so patients with X-linked hyper IgM syndrome (XHIM) have defective cellular immunity and are also susceptible to all kinds of infections, particularly opportunistic infections and to some types of cancer.
With the unusually high T-cell activity in Kolt’s blood, there is a possibility that there is delayed engraftment (not likely, but will be retested in two months), and that Kolt has created a tolerance to Stephanie’s immune system. When looking at the four possible options from the beginning, it looks like we are currently between options two and three. With Kolt appearing to have taken a portion of Stephanie’s immune system, and having tolerance to her, it would make her a much more likely candidate for a subsequent bone marrow transplant. Since it is only 2% though, we are not sure quite which way the T-cells are going. These will once again be retested in October when Stephanie returns to Philadelphia.
The follow up in October, will consist of checking engraftment, in order to see if anything has improved, as well as checking the tolerance levels to ensure they are still compatible with Stephanie. The benefit to having tolerance, is that if/when a follow up bone marrow transplant occurs, if we can use Stephanie’s bone marrow, we will probably not have to go through the traditional transplant process of steroids, chemo, etc. Additionally, the 6 month follow up is still pending as we are not sure what will happen in October.
Locally, we still need to meet with an immunologist and be careful of opportunistic infections. Since his immune system will not adapt and learn from the microbes that he is exposed to, we also have to be more aware of who he interacts with. Enteroviruses seem to be the biggest deal with Hyper-IgM children, (hand foot and mouth, coxsackie, polio, etc.) as they create opportunistic infections. Some members of the Hyper-IgM community start IV IgG around 6 weeks old, as antibodies from the breast milk have a chance of decreasing, but it varies between doctors and patients.
In the grand scheme of things, even though he has not been declared cured from Hyper-IgM due to the in utero transplant, we are still glad that we have gone through the process and were able to meet with Dr. Flake and the whole team at CHOP. They have been nothing but amazing. Since there is still a chance of improvement, and a possibility to avoid the more aggressive bone marrow transplant, we are excited and hopeful for our options. The researchers have been going through the steps and applications looking to see where things might be tweaked for the next child, and we are grateful that we have been able to be a part of the process, and hope that they will be even closer to unlocking the X-linked recessive immunodeficiencies in the future.
We have been blessed with many wonderful patients, friends, and family that have expressed their love to us. Your prayers of support and well wishes have been heard, and have been a support for us as we have gone through this process. We look forward to the additional testing in the next few months, and continue to look forward with faith that things will turn out for the best.
Until then, how about some more pictures!