The doctors told us beforehand that it would not be a permanent solution.
The interview with Jason’s family was conducted in August, so some events described as upcoming will have occurred by the time this newsletter is released.
Jason received a positive newborn screening result for SCID early in the development of California’s SCID newborn screening program. He was diagnosed with X-linked SCID (XSCID). Gene therapy for XSCID newborns was not available. As Jason had no matched sibling or matched unrelated donor, a parental (half-match or haploidentical) transplant without chemotherapy was deemed the best option at the time. While it was predicted that this type of transplant would only offer short term protection, it allowed Jason to grow older and stronger, potentially opening up opportunities for future therapies.
Barb: Why don’t you introduce your whole family and include the age of your 3 children?
Sy: I’m Sy. This is my husband Johnny, and we have 12-year-old “tween” triplets, Lauren, Jason, and Emily.
Barb: Where do you live?
Sy: We live in the Bay Area, in San Mateo, which is close to San Francisco, California.
Barb: How was Jason diagnosed and at what age?
Johnny: Jason was fortunately diagnosed through newborn screening in California. I believe newborn screening was implemented around 2010 in California, thanks to the efforts of Dr. Puck from UCSF. Jason and the girls were born in 2011, so California had implemented newborn screening for SCID just before he was born.
Sy: He was diagnosed with XSCID. (XSCID comes from a defect on the X-chromosome. It is usually carried by the mother and only occurs in boys.) He was probably about two weeks old when we found out. He was admitted to UCSF and he had his stem cell transplant, I believe, within two months of his being born.
Barb: Were either of his sisters a match to donate marrow to Jason?
Sy: No, his sisters were not a match, and they couldn’t find a match in the registry. You know, there aren’t as many Asians registered. Also, I’m Korean, and Johnny’s Chinese, which made it even harder to find a match for Jason. So, I was the donor for him.
Barb: Can you tell me about his transplant? Did he have complete immune reconstitution?
Sy: They didn’t use any conditioning (chemotherapy). He did not have complete reconstitution because his B cells still weren’t doing anything after transplant. He had to remain on IVIG (intravenous infusions of IgG replacement therapy). We eventually switched over to subcutaneous IgG infusions (given under the skin in the subcutaneous tissue).
Barb: At the time of his transplant, what were your expectations? Did you have any indication or discussion on the possibility that he could require another transplant later?
Sy: The doctors told us beforehand that it would not be a permanent solution. I remember clearly, they said because of the type of SCID (XSCID) and the type of treatment he received (a haploidentical transplant without conditioning) he would most likely need another treatment or transplant around 10 to 12 years of age. So, they were pretty spot on, because he’s 12 right now.
So, we just knew in the back of our heads what to expect.
Barb: How would you describe his immune system today? Have you seen a decline?
Johnny: We’re blessed in a way. It’s tough to answer this question, so I’ll try to answer as scientifically as I can.
His T cell count is below the threshold of where doctors are comfortable. So, he’s taking a daily prophylactic medication just to prevent the most common types of lung infections.
I view that as a leading indicator that something needs to be done. Fortunately, he hasn’t gotten seriously ill. And it’s because of these leading indicators that we need to get some treatment done before he gets irreversibly sick in some way.
Sy: We’ve been lucky. He hasn’t been hospitalized or anything. But in the last two years, we do notice come wintertime, that compared to his sisters, his colds and illnesses last longer and he’s hit harder from them. What’s this winter going to be like? There’s that fear. He’s in middle school now and he’s exposed to hundreds of kids every day.
It’s not a matter of “if”, we know it’s just a matter of “when” (he gets sick). When is he going to get hospitalized or become severely ill? We want to prevent that.
Barb: When did you begin to realize that he would likely need another transplant or treatment? How did that feel?
Sy: We could see the trend of his T cells decreasing as early as two years old, but definitely when (his T-cells dropped to their current level) is when they told us, OK, he needs to take a prophylactic medication.
You know, I was thinking, “Oh, my goodness, if he has to take a prophylactic to prevent pneumonia, what else is going to make him sick? What other serious thing could he get?” And we were seeing him get hit harder with colds. Then, it was about 2 years ago that he started getting some weird nausea. It was just unexplained. He would wake up some mornings and just have this nausea, out of nowhere. I know he missed school a couple of times this past school year for that.
There were all these little things, and we thought, “You know, we don’t want to wait”. This all happened right as he was turning 12, the age at which they told us he might need another transplant. So, we thought, we need to do something. We don’t want to wait until he gets pneumonia and ends up in the hospital seriously ill. I feel like that’s too late.
Barb: Have you changed your family plans or been more restrictive because of his declining function?
Johnny: We haven’t. Dr. Puck, and also his infectious disease doctor, advised us to maintain as much of a normal life as possible, which means going to school, hanging out with friends, treating him as a typical kid for the time being. They explained, “Although his T-cell counts have been trending downward, he’s not going to get seriously sick all of a sudden.” They said that it would be gradual and as Sy mentioned, that’s what it has been.
Barb: What was the COVID lockdown like for your family and how did you remove the COVID restrictions?
Sy: Oh my goodness, when COVID hit, I was just beside myself because I thought, “Oh my gosh, you know, there’s no vaccine.” (We’d) watch the news and people are dying and getting that whole inflammatory effect. I mean, it was really scary!
I wanted to just stick him in a box and just keep him locked up in a box or my closet forever until the whole thing was over, but you know, it’s been four years and we’re still dealing with it.
It was terrifying because I just didn’t know how his system was going to take this. I thought if he gets this, he might die. His T-cell levels were pretty low. How was he going to respond? That was really scary.
I’d say we were probably paranoid. No one was coming into our house. Everything was delivered and Clorox wiped as much as I could. We were scared. We just didn’t know what could happen.
When I thought my mom had COVID I was like, “Stay away. I’m sorry, I cannot see you.” Once there were vaccines we said, “OK, we’d like to see our family”. We were making sure everyone tested (negative) before coming over.
But the social part for Jason, he took a really big hit mentally not being around people or his peers. I think that was because of the lockdown and lack of social interaction with people. It was a really hard time for him.
So as much as we try to balance being safe, we also know that, especially at this age, he’s a very social guy, and he really needs the interaction. We just try to find a balance.
Johnny: But here’s a fun fact: All of us have gotten COVD at some point after the vaccine came out, except for Jason. He’s never tested positive for COVID.
Barb: I do give IgG a lot of credit for keeping these patients healthy.
Sy: Exactly! I thank God for all those people who donate the plasma for his medicine.
So, we’ve gone from paranoia about COVID to it being something that is always in the back of our minds. We can’t let go of it, not just because of SCID, but because of where his current immune status is with his T cells. We’ve all been vaccinated, and we just hope that other people are too, but as you know, they’re not all vaccinated. We can only do our part and I’m fine excusing ourselves from events and things if we need to.
Barb: Let’s talk about Jason’s current treatment opportunities. I understand that you’ve received confirmation on a treatment for him. What is being planned?
Sy: We got the green light for gene therapy at NIH (The National Institutes of Health). Jason and I are going in August for the initial screening appointment which includes a lot of blood work and signing consent forms. Then we will go back in September for the actual apheresis (collection of Jason’s stem cells to be used for gene therapy). We’ll talk to the doctors then about exactly what comes after that and what date they will want him back to start the treatment.
It’s happening so fast. They give you a call and say, “Are you available next week?” We just said, “Sure! We’re ready to drop everything and go.” We don’t want to wait and lose our place (in line).
In March of this year, they initially said they were ready for us, but then we didn’t hear anything from them. We’d contact them and they would say “We’re not going to forget about you, but just live your lives for the next three months and we’ll contact you when we’re ready again.”
So, this time we are getting on that plane and going.
Barb: Gene therapy for SCID involves transferring a normal gene into a patient’s hematopoietic stem cells (HSCs) which have been removed from the blood stream using a process called apheresis. The cells are then reintroduced (by an IV) back into the body. This approach aims to offer the advantages of allogeneic transplantation (transplanting cells from a donor), without the risks of graft rejection. However, the history of XSCID gene therapy has had its ups and downs. While studies performed more than 20 years ago showed the feasibility of the therapy, successfully correcting the T cell defects, there was an occurrence of vector-related leukemia in a few patients. Since then, new vectors and isolators have been tested and incorporated into the latest trials in order to enhance the outcome and reduce the potential for side effects.
Barb: So, Jason’s upcoming treatment plan is a clinical trial. As his advocates, how important do you feel it’s been for you to be relentless in your efforts to ensure he was accepted into this trial? Do you feel like you had to be the ones pushing to get him into the trial?
Johnny: Yes, I think combined with the support of Dr. Puck and others, it was really important to let the doctors at NIH know that we were very excited, enthusiastic, and eager to participate. I think it was important that we let them know that we were very flexible in terms of timelines and able to accommodate their requests. We were being responsive to them. I think it was important to make sure we were always on their minds. It was important to make sure they knew we really wanted to do this. So, we tried to be flexible, serious, and hopefully pleasant to deal with.
Sy: I don’t think this would have happened without us putting in the effort and I have to give credit to SCID Angels for helping guide us. We learned that we had to contact them constantly. I was contacting them so much I was worried, “Are they going to hate me?” But I want them to know that we are serious. I want him on the list, at the top of the list, because we are ready to drop everything and go. That’s how important this is. So, when she said, “Can you come next week?” I said, “Yes!”.
I think you have to (advocate), not just in this case, but in any healthcare. What’s the saying? The squeaky wheel, you know, I think it’s true. You have to be very vocal, and you have to be after them, otherwise, they have other priorities, and they have other people wanting to be in the trial. You have to be relentless. Jason can’t do that. He’s only 12, so he’s not going to be emailing and calling the doctors. We have to be his advocates. Our approach was, “You’re not going to forget about us. You’re going to see my email every Monday”.
Barb: I think this is an important message for other parents. I don’t think everyone realizes how limited the spaces are in these clinical trials. I think families need to hear how you continued to advocate for Jason, not just once, but repeatedly writing to doctors you didn’t really know.
Have you discussed with Jason the potential side effects of the treatment, particularly the side effects of chemotherapy?
Johnny: I think he knows some, but perhaps not all of the side effects. I think the major one he knows about for Busulfan, which is a chemotherapy drug, is that it may affect his fertility down the line. We are having a sample of his semen preserved by a fertility clinic so he will have that option.
Sy: We went to the same fertility clinic where I went and where we were successful in becoming pregnant with our 3 children. I’m glad he was able to do that because we don’t know if the effects will make him sterile and we explained that.
I’m very upfront. I feel like he has a good depth of understanding for his age, maybe because he’s had SCID his whole life and I’m very frank with him. I’ve explained the whole process of how we’re going on our first visit to NIH. I’ve explained the apheresis and how he’ll get the GCSF shots (a growth factor to stimulate his bone marrow to produce more stem cells) for about 5 days. How they’re going to place a central line (large vein IV line) which they will use to collect his cells. I’ve explained about chemo and that there’s a really good chance his hair is going to fall out, but it’ll grow back. I told him how the chemotherapy could make him sick.
How much he remembers of all this, I don’t know but we’ll probably have more discussions as we get closer to the date. We don’t try to tiptoe around what it could be like, and I feel like he’s old enough and he has a good level of understanding so that we can be upfront with him and say, “This is what might happen.” So, I think he knows.
But if you ask him, he’ll probably say, “They didn’t tell me anything.”
Barb: Has Jason’s medical journey affected your relationship with each other?
Johnny: This is tough to answer because there were other factors, right? Jason was basically diagnosed with SCID as soon as he was born. But that wasn’t the only big change in life, right? We went from no kids to three kids, just like that. It was a big change in our relationship from being married with no kids to being married with three kids.
Sy: I think that was a bigger change than Jason’s SCID diagnosis, just having 3 kids all of a sudden. But the diagnosis was a big screwball thrown at us.
Johnny: We had no chance to adjust, we didn’t just jump from having no kids to having three kids, but we jumped from having no kids; to having three kids; to having three kids, but one is in the hospital.
Jason was in the hospital pretty much as soon as he was born. So that was huge, and we still had to take care of Lauren and Emily who were infants and Jason was in isolation at UCSF. Sy and I alternated days of visits to Jason while the other one stayed at home with our daughters. It was a whirlwind.
Sy: Overall, I think we’ve done a good job tag-teaming. We have our own strengths, and we balance each other out. So, I can’t say that it has damaged our relationship, but it has changed (our relationship). I can imagine that whether it’s a medical condition or having multiples, it is definitely up there for stressing a relationship. We’ve certainly had some big things thrown at us, but we’re a good team. We’ve pulled through it and we’re still alive.
Barb: What advice would you give another parent or caregiver who wants to learn more about a clinical trial or have their child accepted into a currently recruiting trial? Any words of advice or things you’ve learned that you can share?
Johnny: One is to ask the SCID community what they know. Somebody knows something. Ask for introductions. I think you need to take the initiative. It’s not for the timid. I think we mentioned earlier that the squeaky wheel gets the grease, and you should do your best to develop relationships with the community and with the doctors. Let them know what situation you’re in or your loved one is in.
Be persistent, both within the community and also with the doctors. It’s not personal. People are extremely busy. They have a lot going on. So, if you send an email to someone and you don’t get a response, don’t take it personally. I encourage you to be proactive in reaching out again. Just be persistent.
Sy: Like SCID Angels told us, “Be relentless”.
And don’t give up. Definitely stay within the community and stay connected. Don’t lose that support, because it’s the support and knowledge. You just can’t find that anywhere else.
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