The Parent’s Guide to Cord Blood Foundation recently announced that Cryo-Cell and its long-time partner, a Duke pediatric cell therapy team, have made a key change. They will begin offering infusions of unrelated, unproven cord blood to pediatric patients with cerebral palsy (CP). These are called donor infusions. Up until now, they had mainly focused on children’s own cord blood or sibling units.
The fact that Cryo-Cell gives money to the Parent’s Guide to Cord Blood Foundation is important context. The foundation’s website often has the first news on these kinds of changes.
(Note that I had this post mostly written when news broke last week that puts doubt to the future of Cryo-Cell and Duke partnership, which may affect the plans described here for donor blood. The two are in a legal conflict.)
The Duke pediatric cell therapy team
Some of the new donor blood infusions reportedly will be done via the Duke team led by Professor Joanne Kurtzberg. In addition, more broadly, the donor cord blood will be administered via Duke’s expanded access program or EAP.
This post briefly goes through some background. It also explains my questions and concerns about this change. An overriding question is the extent to which this new plan reflects only a primary goal to help children with CP versus a main focus on corporate interests.
I believe it is probably a complicated combination of both along with perhaps some overzealous faith in cord blood.
Duke & Cryo-Cell seek to infuse far more kids
I am very upbeat about the general potential of cord blood. However, so far other than its use in place of bone marrow and hematopoietic stem cell transplants, such as after chemo for cancers or its use in other blood disorders, nothing else has been proven to work.
For instance, it is not clear that cord blood generally helps kids with CP. The data suggest that there could be a benefit for some subset of kids with CP and even that is not a sure thing. Based on the data that I’ve seen, I believe most probably will not benefit.
If the odds of benefit are low for most kids who might get infused, why proceed at all, whether using autologous or donor cord blood? I want to emphasize that there’s a huge need for new, effective approaches to CP. Talking to families, I understand and respect their openness to try new things like cord blood.
However, in my view, Cryo-Cell and Duke should not just be given the benefit of the doubt on their plans here. In particular, their past decisions related to cord blood for autism within that same EAP (more on that below) raise doubts for me more generally. For more information on this firm, see my Cryo-Cell review.
Why the switch by Cryo-Cell and Duke?
Why the change to donor cord blood now?
The Foundation website says of the new plan (emphasis mine):
“The reason this change was made now is to align the EAP with a phase 3, multicenter, clinical trial sponsored by Cryo-Cell International that will be launched in 2024. The phase 3 trial will study the treatment of young children that have cerebral palsy with allogeneic, unrelated, publicly banked cord blood. Cryo-Cell is currently working through the final FDA approvals for this phase 3 trial. Duke will be one of the trial locations, and hence the Duke EAP was modified to provide a comparable compassionate treatment for children with cerebral palsy that do not qualify for the clinical trial.”
Is this a solid rationale for the change? It’s hard to say.
The trial might be justified and that’s something that could be discussed or even debated, but shouldn’t the trial be done before an EAP transfuses potentially a thousand or more kids? What if the trial finds a few years down the road that donor cord blood is not generally helpful for CP and yet they’ve already transfused all these kids through the EAP?
I have more on the possible justifications for donor cord blood use below.
Not yet a CP treatment but called that
It also concerns me that Duke, Cryo-Cell, and their supporters continue to use the word “treatment” for what the EAP offers (see the Foundation quote above). The evidence that the cord cells here are an effective treatment for CP or other conditions is not conclusive:
“Duke already has a waiting list of thousands of families that have made inquiries about the EAP. They are working through the process of notifying each family which has a child with a qualifying diagnosis but which did not have a cord blood unit to bring to the program. Now those families are eligible to be treated with a donated cord blood unit.”
While the EAP must have FDA approval, this intervention for CP does not have final FDA approval as a possible new treatment. For that reason, I believe that “treatment” is the wrong word to use as it risks giving false hope. For years some of this group called the cord blood infusions for autism a “treatment” as well. It seems it wasn’t.
Furthermore, the advocates of cord blood for pediatric neurological conditions keep emphasizing how there are thousands of families on waiting lists to get cord blood for their kids through the EAP and implying that giving more access must be a good thing.
Does this change make sense for the kids and their families?
There is an implication with the switch to donor cord blood that it would increase access and that’d be a positive.
But how is more access to an unproven cell therapy product that has yielded mixed data a good thing? It could be a positive if you as a kid with CP (or a parent of one) are one of those who might benefit, but it’s not clear how to identify such possible more-likely-to-benefit participants and whether they are the only ones that Cryo-Cell will infuse through the modified EAP.
Let’s say that we know for sure 10-20% of children with CP could benefit modestly but significantly from donor cord blood, then another tough question is whether the potential to help that relatively small number of kids with CP balances out the downsides to infusing so many kids with CP with donor cord blood, most of whom probably will not benefit. It’s a tough question. Would it make it any easier to answer if you throw in the fact that all those families would have to pay a large sum, perhaps around $15,000, just to have their child get the unproven infusion?
Moving forward, the overall team should only infuse those kids with the best chance for benefit, and if they aren’t sure which ones those might be, they should be transparent about that too.
How is informed consent being handled here with the EAP? How much false hope might there be?
What do the data tell us?
What do the trials indicate so far more specifically?
See my 2017 post on the autologous cord blood for CP trial results where I didn’t see the results as particularly encouraging. A subset of kids might benefit, but it wasn’t conclusive. Kurtzberg’s team has also done trial work on allogeneic cord blood for various conditions including CP. Their paper on the donor cord blood for CP trial reflects mixed results at best in my view.
It’s not a super solid foundation on which to base giving donor cord blood to hundreds or thousands of more kids.
When we think about a possible new approach to a health condition, we should also consider whether there’s a logical mechanism, preferably consistent with the data. What would be the mechanism by which donor cord blood helps CP? There are no clear data on this point either. Direct repair to the brain? But it’s uncertain if enough cells get in there and engraft.
An immune mechanism? Something else?
These kinds of things are possible yet unproven, meaning there isn’t a very strong rationale here.
How much is corporate-driven?
Let’s circle back to the big picture question: why donor cord blood now? There are plausible logical reasons that get into more specifics.
It is possible, for instance, that in some cases the donor cord blood could have far more cells than the autologous unit for any particular child. We don’t know for sure yet that more cells are better, but that’s at least plausible.
Another possibility is that the families of many kids with CP either may not have banked their cord blood or it has already been tried and hence is no longer available.
Some cord blood units, even if still banked and unused, may be unusable due to contamination or other issues. For these kinds of reasons, donor cord blood might be the only option. I get that, but as a skeptical scientist, I also can’t help but wonder about corporate motives here.
If potential customers (the kids and their families) are no longer limited to using just their own cord blood, that could lead to far more customers for Cryo-Cell. In turn, Duke stands to potentially make millions of dollars if Cryo-Cell can sell more pediatric “treatments” at the firm’s planned infusion clinic in the future. See an image above that I captured from a past Cryo-Cell corporate presentation that showed their focus on revenue.
Why is money such a potentially big factor here? Duke and Cryo-Cell have a mega deal worth millions of dollars that depends on certain milestones including some dependent on the EAP.
I wonder if families are told about the multi-million dollar deal?
Cryo-Cell & Duke’s past EAP record on autism is a red flag
I also can’t get past the fact, as noted earlier, that the Duke team used the EAP previously to infuse hundreds of autistic kids with unproven cord blood. This went on for many years, racking up probably millions in costs to families. Again, this was supposedly a “treatment” but it wasn’t proven or FDA-approved on that level.
Things changed in a big way in late 2022. The autism part of the Duke EAP was halted.
The reason was that Duke’s data didn’t support cord blood for autism. It was a “treatment” that wasn’t a treatment. It didn’t work. Despite the team’s negative data and discouraging results from other trial work, as best as I can tell Duke continued infusing kids with autism via the EAP, perhaps for one or more additional years.
I believe that was a mistake and probably did harm. It makes me question the motivations of the new form of the EAP today on the CP front. Looking ahead, if the newer trial data on allogeneic cord blood for CP end up mostly discouraging, will the team just keep the EAP going for CP for months or years after they have such negative data? Clinging to a subset of data that maybe is a hint of benefit for just some in post-hoc analysis? I hope not, but it’s a worry.
Faith vs. data
Finally, after following the Duke and Cryo-Cell efforts in this space now for a long time, I have to wonder if another key driver here is based on an intense kind of faith in cord blood.
I get the sense that there is an almost religious belief that cord blood MUST be effective for kids with autism, CP, and potentially other neurological conditions.
That’s not how biomedical science is supposed to work. We scientists are taught that we must not get too attached to our hypothesis.
Also, if our data disprove our ideas, we have to listen to the data and move on.
There are some risks to the Cryo-Cell plan
There also needs to be full transparency with families about potential risks and benefits including when getting cells through an EAP.
While autologous or partially matched cord blood infusions are relatively safe, they are not risk-free. Donor cells are probably reasonably safe but they come with risks too.
One kind of risk comes from the sedation of the kids for the infusion. Published data indicated there have been some negative outcomes related to that. Infusing very large numbers of kids with donor blood in the EAP could reveal new risks too.
Looking ahead on Cryo-Cell and Duke
There’s nothing wrong with clinic research ultimately leading to a firm making money. That’s actually good. We need biotechs to thrive in the regenerative medicine space. The field is largely hamstrung if we can’t partner with biotechs in productive ways. If those biotechs don’t make profits, fewer people will benefit from cell and other regenerative therapies.
At the same time, premature deployment of unproven therapies can be risky, including through EAPs. Actions such as calling unproven interventions offered by EAPs by the term “treatments” have concrete downsides too like false hope.
Finally, again, I don’t know if the new donor cord blood plan will still happen somehow given the recent disclosure by Cryo-Cell that it is seeking arbitration after what it calls fraudulent activity by Duke related to their partnership. Could Cryo-Cell somehow proceed without Duke? If that was the path forward, it could be delayed by years.