Baby Hayden Medical Journey – Background and Day 1

As many of you know, we (Dr. Chase and Stephanie Hayden) are pregnant and expecting our 4th child in August 2017. If you have seen any of our posts on Facebook, you may have some idea as to what s going on, but if you have not, this is the quick summary, as well as the progress/journey that we have started on. Stephanie is a carrier of a genetic immune deficiency called X-Linked Hyper IgM Syndrome. Since it is an X-linked condition, and females have two X chromosomes, Stephanie does not experience any symptoms. Her father had the condition, so his X chromosome was affected, and his Y chromosome was not involved in immune regulation.

As a known carrier for an X linked genetic disorder, with every conception, we go through specific genetic tests, identified through a Chorionic Villus Sampling (CVS), normally at 10 weeks, though sometimes as late as 12 weeks. The information from the CVS is immediately screened for the baby’s gender, and if it is a boy, additional testing is performed to identify the genetic mutation, if present. Our oldest son (10 years old) was negative for Hyper IgM, and our other two children are girls, so testing did not progress to identify if they are carriers for the condition or not. (That will come later in life so they can know what to expect once they start having kids.)

In the past, we have worked with Duke University researchers and geneticists, as well as the doctor that worked with Stephanie’s father before he passed. Duke University has been going through research grants over the last 10-ish years, specifically related to Hyper IgM Syndrome, so when we found out that we were pregnant and called them up, we were disappointed to hear that they no longer were offering the program, and had lost funding less than 30 days before we contacted them due to lack of participation within the program. Since the Duke researchers were unable to help, Stephanie started looking for other options, and stumbled across an article about some doctors in San Francisco that were doing in utero stem cell transplants. Stephanie reached out to one doctor in San Francisco, and that doctor was able to put feelers out and then was able to get us in contact with a doctor and researcher at Children’s Hospital of Philadelphia (CHOP) and some potentially good treatment options.

Generally speaking, the treatment of Hyper IgM has included life long intravenous IgG (IV IgG). This means that every few weeks, individuals with Hyper IgM would have to go through infusions for their whole life. Stephanie has family members that currently go through this process, and for the most part, they are able to live normal, every day lives. An additional treatment is through the process of a bone marrow transplant, that happens once the boy with Hyper IgM Syndrome is about 6 months old or older. This involves chemotherapy, isolation from potential infections, and a recovery period of about a year to ensure that graft verses host disease does not set in. One of Stephanie’s nephews went through this process, and now has a functional immune system, and does not need IV IgG anymore. There were a few side effects from the procedure, specifically related to hormonal issues. He is now 15-ish years old and doing well immune wise. There have been other children with Hyper IgM Syndrome with complications from the bone marrow transplant (some much more sever than others), and if we can avoid it, we will try to.

The third potential treatment option for Hyper IgM Syndrome is what brings us to Philadelphia. Dr. Alan Flake is a specialist in neonatal surgery, and has been researching immune deficiencies and neonatal surgical options that can potentially reverse immune issues. Additionally, the doctor that works with Dr. Flake, Dr. Mark Johnson, has helped to develop many of the neonatal treatment options for compromised fetuses. Together, they are proposing a solution that has worked well in multiple animal studies (mice, rat, monkey, dog, and sheep) in order to provide an alternative to lifelong IV IgG and/or a bone marrow transplant (with accompanying chemotherapy, etc). Our goal is to perform an In Utero Stem Cell Transplant with the baby, in order to override the soon to develop immune system.

The general process that we have discussed will be as follows:

• Stephanie will begin taking a medication called G-CSF (granulocyte colony stimulating factor) which is frequently used after chemotherapy, or before stem cell transplant therapy. This medication will be injected into Stephanie daily for 5 days, and it will help her bone marrow to produce a bunch of additional stem cells. This medication does two big things: 1.) it increases Stephanie’s undifferentiated stem cells, and 2.) causes the fetus’s bone marrow to be receptive to therapy (essentially it unlocks some of the binding sites so that something else can come in and rearrange things)
• After 5 days of injections, she will then go through a process called Apheresis Blood Collection. This will pass her blood through one IV, go through a machine to suck out the stem cells, and then return her blood back to her through another IV. They are estimating that they will need to run all of her blood through the machine twice in order to get the number of stem cells needed for the procedure. This is sometimes performed by taking blood from one arm, and returning it to the other arm. In our particular situation, it was determined that a central line is the better option.
• After the stem cells are collected, they will then be cultured over night in a special machine that they have here that they have been doing their research with. This machine will start the process of getting everything ready for the in utero stem cell transplant.
  • Side note: When we were originally discussing this option with Dr. Flake over the phone, the use of this machine was discussed. The day before we left to come to Philadelphia, Dr. Flake called to let us know that we may not be able to do the procedure anymore due to the research basis of the machine needed for this procedure. Even though the hospital has the machine and uses it all the time, it is only approved for research with animals and they did not have FDA approval for it to be used with us (or possibly for Hyper IgM… the details are missing). Needless to say, a last minute phone call, and stack of papers had to be submitted to the FDA in order for us to get special permission to use this machine for our procedure. The FDA approval came through in less than 24 hours, and when meeting with Dr. Flake, he mentioned that it was a miracle that we got it approved. (I am not sure if he meant approved in general, or approved in a 24 hour period, either way we are excited and grateful for the approval!)
• Once the stem cells are collected, cultured, and prepared for implantation, the next step involves Dr. Mark Johnson injecting the stem cells into the fetus’ heart. It sounds kinda crazy that we would willingly take a needle to the heart of the baby, but by over saturating the circulation with Stephanie’s stem cells, and with the G-CSF medication, the fetus is primed and ready to latch on to the cells, and use them to start rebuilding the immune system. A few big things happen as a result of doing it at 16 weeks gestation.
  • The baby’s thymus will cycle through Stephanie’s cells and become immune-tolerant with Stephanie’s immune system. This is a big deal because if the cells do not take like we are expecting, it will allow Stephanie to have an immune system “twin” in the baby, so future treatments (like bone marrow transplant if needed) would take much easier, and not require as much medication, a separate bone marrow donor, etc.
  • Since this is done so early in the baby’s development, the stem cells have a greater chance of taking, and replacing the defective X gene
  • Since the injection is done at 16 weeks, instead of earlier, it allows for the lowest chance of complication from the procedure. Dr. Johnson has performed much more extensive and invasive in utero cardiac procedures, and is estimating the risk of this one to be less than 5% chance of complication.
• Following the injection of stem cells into the fetus’ heart, Stephanie will continue to remain in Philadelphia for about a week for monitoring, ultrasounds, etc.
• Throughout the pregnancy in Texas, she will start meeting with a maternal fetal specialist for continue ultrasound checkups every 4 weeks or so. These ultrasounds are to identify graft versus host disease in the baby, if it happens.
• Around 32-34 weeks, assuming there are no complications, Stephanie and the kids will then come back to Philadelphia and remain here until the baby is delivered.

There are four potential outcomes from this procedure:

• 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.

Obviously we are hopeful, and at peace with our decision to work with CHOP and Drs. Flake and Johnson. We have known about Hyper IgM since before getting married, and always knew that there would potentially be complications with our children. Up until recently, something like an in utero transplant was not an option, and this will be the first time in medical history that this procedure will have ever been done for Hyper IgM Syndrome. Due to the uniqueness of our situation, the research associated with the procedure, the specialties and doctors involved, and the desire to provide a viable treatment option to genetically compromised immunological patients, Children’s Hospital of Philadelphia has done an awesome job of working with us. They have already informed us that they will be helping out with some of the expenses, which is also a great blessing since this will be an expensive process (the 5 day dose of medications for Stephanie is $1000!). I think they are excited to be the first center to potentially cure someone’s genetically compromised immune system with an in utero stem cell transplant.

More details to come as we find out about them, but for now this is what we know, and how we are proceeding.

Note: if you were wondering why I am posting about this process on the office blog, it is because most of our patients have been asking about Stephanie, and the process, and this is an easy place to document what is going on, and for us to be able to share the details/updates easily with other people. Thanks for your prayers and concerns!

To see the second post, CLICK HERE.