Questions about how the world works rise in our minds every day. Most people just “google-it” for an answer and for most simple questions this suffices. Sometimes a question arises that is more complex than simple fact-checking, and we are asked to form an opinion based on a range of knowledge. I faced one such question about a month ago. I was leaving a northern Toronto hospital in my ambulance when my partner and I spied a vehicle from one of the many private umbilical cord blood (UCB) collectors. My partner is going to have a baby soon and he and his wife were considering collecting cord blood. He asked me if I had an opinion. I had none: this was the first I had heard of it.
Of course, I did not let my own ignorance get in the way. The tools of skeptical scientific inquiry are available to all, and with a little bit of effort I believe it is possible to form at least a general opinion on most everyday science questions. My first stop was to find out why the heck people were collecting cord blood in the first place.
The answer was pretty obvious; the umbilical cord contains stem cells; specifically, hematopoietic stem cells. These are the cells that can grow into all forms of blood cells in the body. They are sought after for transplantation in many blood disorders, like leukemia and sickle cell anemia. This page at the National Institute for Health in the U.S gives a great run down on HSCs and their use in transplant therapy. This type of stem cells are traditionally collected from bone marrow (BM), or, with some coaxing, from peripheral blood (PB) the kind taken out of your arm. UCB has been collected and stored routinely since the mid 90’s and is used commonly for allogeneic – or non-related – patients, who are usually children due to the small amount of cells collected from the UCB.
The thing about UCB is that it is taken from a source that is usually considered medical waste, and it has proven to be a high quality graft , when compared to BM or PB derived stem cells. With UCB, fewer cells are required for the graft and there is a lower chance of graft vs. host disease, or GvHD, where the grafted cells that turn into white blood cells start to attack the host’s cells and destroy them. This has been used as advantage in cancers where the graft is used to attack the cancer cells in the host. One drawback with using UCB is that it takes longer to engraft and multiply in the host, which leaves the patient at risk for infection longer. This risk is often outweighed by the advantages of availability and lower required matching, but is not insignificant.
The source for UBC for standard therapy is from public cord blood banks like this one and this one in Canada, and once a donor has been matched, is available within days. This is much faster than the 3-4 months it takes to match bone marrow or peripheral blood. Any tissue must be matched closely between donor and recipient to prevent rejection of the cells by the body. This ID is through the so-called HLA, or human leukocyte antigen, a protein on the surface of the cell that identifies it as “self” or “non-self” to the immune system. This is often ensured by using a family member or sibling as the donor, but with larger collections, this is still possible with un-related donors, and is routine. The advantage with UBC is that you require a lesser match, only 67%, than bone marrow or peripheral blood, at 83 %. So, we have found that allogeneic, or unrelated, grafting is the standard, and public, non-profit, cord blood banks have been storing and distributing this stuff for years. Enter the private sector.
The private sector, as it is so good at, identified the niche in UCB collection that public cord blood banks were not focusing on: the private collection of your own cord blood at birth and its storage for future use by you. The Alberta Cord Blood Bank did store UCB for siblings with known or expected blood disorders, but this service was discontinued in 2007, about a year or so after a private UCB bank started storing their collection in the same facility as the ACBB; funny, that.
The private companies have been focused on promoting storing blood for autologous grafts: blood collected from the patient for re-injection into the same patient, although many also make the argument that it should be stored for use with other family members. The cost is not inconsiderable, the average being around Can $3000.00 for collection and storage for 18 years. The hard sell is “biological insurance,” to have this back-up in case your child or his or her siblings requires a stem cell transplant. They make the all of the medical arguments about UCB in general that are listed above. The private companies insist that you have one chance to collect, that the UBC dramatically increases the chances of having a matching sample for other family members and they paint the picture of a future in which many genetic disorders may be cured by such samples. Most of the companies also make a future promise statement, that there are non-blood disorders for which stem cells collected can be of use for treatment. Finally, they all insist that collection is safe and poses no threat to mom or baby. These claims seemed reasonable and not overhyped, for most of them, so I started to look into the facts.
My first stop was the Society of Obstetricians and Gynecologists of Canada, the folks that set the standards of care in Obs/Gyn. As a generalist and an expert in a very narrow chasm of knowledge, I have to rely upon experts. There a few criteria we can use to judge expert opinion, I find. The first is to look for consensus. One expert can be refuted by another, but a consensus has a much higher chance of being closer to the truth. Next, the knowledge that this consensus is built upon must be freely accessible to the general person, or at least to those with a library card. Lastly, I tend to trust those with professional affiliation, the more government oversight the better, with a good complaints process. The SOGC is a good example of this type or organization, so I combed through their position paper and guidelines.
The SOGC recommends the use of UCB, when bone marrow or peripheral blood is not available, that is clear. As well, they like it for allogeneic grafting and encourage the altruistic collection of UCB as long as the safety of the newborn and mom is never compromised. Excellent! What about collection and storage of UCB for autologous transplant? The SOGC is quite clear here, and they don’t advise it:
“6. Collection and long-term storage of umbilical cord blood for autologous donation is not recommended because of the limited indications and lack of scientific evidence to support the practice”
They are quite sure that in the absence of a matching donor for BM or PB and in situations where the patient is seriously ill and cannot wait for a matching donor to appear, UCB, even the mismatched version is a good choice for allotropic donation and can improve patient outcomes. And they even go as far as to recommend private collection and storage if the family has a history of blood disorders, like sickle cell anemia or lymphoma. They have also found that collection is very safe for mom and baby, although, this paper identifies a problem when it may interfere with the collection of blood gases to identify acidosis in baby.
The evidence in favour of private collection and storage is very thin, and as such has not become the standard of care in any jurisdiction. This has not been the practice for many reasons, the most glaring being that if it was a genetic or congenital condition that caused the disease in the first place, chances are the HSCs that were collected from the individual have the same genetic or congenital problem, like leukemia, lymphoma or sickle cell disease. As well, the yield of stem cells increases if you shorten the time between delivery of the baby and cutting the cord, whereas the consensus today is that waiting longer to cut the umbilical cord has better outcomes for the baby. If a patient had contracted the services of a company to have the blood stored, there may be a conflict between what the parent wants and the health of the baby. The chances of using the tissue are very small as well, anywhere from 1:1400 to 1:20 000. This paper outlines the current risks as identified in the British NHS and the problems are similar here. I was perturbed at the argument that you have one chance to collect. If you do not collect stem cells at the birth, you DO have a chance to collect HSC’s from BM or PB for autologous transplant, which is the standard of care now.
I used pubmed in the US as my main research tool, but also included the Cochrane database. Most research into cord blood usage centered around the use of UCB from public blood banks and due to the decreased need for a perfect HLA-match, and it was shown in this recent review to be as good as BM or PB in overall outcomes. The gold-standard would be perfectly matched UCB but given the risks in collection and usage of autologous grafts, and the ease with which finding a 67% match is possible, unrelated donors are a viable and safe option, and have good outcomes for baby.
The claim that the cord blood can be used to treat other non-blood related donors is an interesting one, but remains a pipe dream. The cells that are used here are not the hematopoietic stem cells, but are other stem cell lines that are found in smaller numbers and able to produce connective, muscle and bone, and organ tissues. The problem is they have not been shown to survive the freezing process very well, having yields of less than 50%, and we no good way to multiply the cells outside of the body. There is good evidence to show that fresh cord blood could be very useful in treating congenital disorders but the frozen and stored variety has shown to be very poor: the cells aggregate after thawing and are not very useful. This has not stopped Create from developing a proprietary process called Peristem in which these cells, specifically mesenchymal stem cells, are collected and stored. I could find no publications on this process or the use of these cells on a pubmed search using the medical director’s name and cord blood, nor the “Peristem” term either. I do not have sufficient information to determine if the various labs are good or bad at their storage, but it certainly appears as if the Create lab is top notch and very committed to the best storage and all of the labs have the appropriate certifications, at least according to their websites. My concern is the promises that are being made as to the future use of these tissues. I am not the only one who has these concerns. In a December 2009 review from pubmed, the authors conclude that
“Experiments in cell culture and in animal models suggest that these cells might be of therapeutic use in regenerative medicine, but also show that this potential can be realized only if the cells are not cryopreserved”
You can’t put it more succinctly than that. That same review suggested that a UCB sample size of 50 000 is needed to serve a population of 60 million people for all HLA types, given that exact typing is not necessary and this supports the recommendations by the SOGC. In this Oct. 2009 article in the British Journal of Haematology, the availability of unrelated donors is very high:
“With approximately 350 000 units banked worldwide (http://www.bmdw.org), the addition of UCB to the available stem cell sources makes it possible for nearly everyone who requires an HSCT to have a suitable donor available.”
So, in this (exhausting, if not exhaustive) review of umbilical cord blood collection and storage, what have I learned. The most obvious is that hematopoietic stem cells are becoming a standard of care for those which bone marrow and peripheral blood is neither matched well, nor available immediately. As well, that private banking over-promises and is largely unnecessary for those with no known or expected blood disorders, but that parents should seriously consider donating the cord blood from the birth of their baby to a public non-profit bank to ensure adequate supply of these needed tissues.
All of the reviews both in Europe and Canada that I had found warn that doctors, midwives, and other birthing professionals should be prepared to fully inform their patients when it comes to UCB collection and storage. The $3000 price tag could, in my opinion, be better spent investing in an RESP instead of unnecessary biological insurance. More-over, when a private company starts to offer services that find the gap in public health and attempt to exploit it, be skeptical and do your research.