Singapore Advertises Cord Blood Stem Cell Banking (Part 1)

Last week in the Singapore Straits Times, there were two snippets about cord blood stem cell banking. The first one was a news piece on the Singapore public cord blood bank (entitled Cord Blood Bank has saved 21 lives**) which was campaigning for an increase in units (arguably an ad in itself). The other snippet was an ad by a local private Singapore Cord Blood Bank Cordlife. The ad appeared 2 days after the news article and I don't think its a coincidence to keep the conversation and interest in Singaporean's minds.

The first article from the Singapore Cord Blood Bank at a press conference reveals quite a lot about what its like to be an operator of a public bank:

How many cord blood stem cell units have been released and where have they gone?

"In the 3 years it has been open, the Singapore Cord Blood Bank has saved 21 lives - here and overseas... a 22nd donation was winging its way over to France"

"Of the 21 recipients, 12 were patients here while the other nine were ethnic Asians in Europe and Malaysia."

Comment: 21 cord blood units utilized in transplantation is very respectable for a small bank. Financially, at a purchase price of SGD 26,000 per unit in Singapore, the SCBB would have generated SGD 312,000 in revenue for the 12 Singaporean patients and another approximately SGD 320,000 from the 9 overseas patients (assumption is that these patients came through the NMDP network and paid the standard price). That would bring the SCBB's total revenue to SGD 632,000 or slightly more than this.


How many Singaporeans have donated cord blood and how many of those have been successfully banked?

"The repository has been able to bank about half of the 9,000 donations so far. Donations sometimes do not yield enough stem cells to be viable*."

Comment: The yield of 50% is very much in line with what I've heard from other public cord blood banks. However the article doesn't explain that units are discarded due to bacterial / viral contamination (let's not forget that vaginal flora and fauna can be quite substantial) and that the cord blood bank sets its own guidelines as to the volume and/ or cell count required at the beginning before they proceed to process the unit.

As a guide, at the time of receipt of the cord blood unit, most public cord blood banks insist on a minimum volume of 100 mls or total cell counts exceeding 1 billion. The rationale for this is that the cord blood unit needs to be at a level high enough to treat an adult (including caucasian weight & bigger sized asians), otherwise its not worth keeping (bearing in mind that this inventory can and most certainly will take years to clear). *Thus the term "viable" in the article refers to the unit's chances of being used.

Targets for the Singapore Cord Blood Bank?

"An earlier target of banking 10,000 samples by next year has been extended to 2013 said Mr. Sobak (SCBB's CEO and COO of SingHealth), since its been harder to get good-quality donations."

Comment: 10,000 units in the tank is an ambitious target but let's consider the following points:

1) The SCBB is based in the KK Women's and Children's Hospital, which alone delivers the vast majority of Singaporean babies has handled almost 40,000 babies at its peak, but more likely in the range of fifteen to twenty thousand now.

If the SCBB were able to collect all of the cord blood units from all the babies delivered there per year, without approaching any other hospitals (and discounting the 50%) the SCBB would have had about twenty thousand or so units by now. But, that would mean that they would have been working at a pace of 20 units per day seven days a week, all year round for 3 years. Hence the limitation of time, processing space and cost all plays a part in the operational capacity. [4 years more for 5000 units]

2) Cordlife, the first local Singaporean private cord blood bank started in 2001 only recently achieved 13,000 units in 2008 (announced in an ad) and claim only a 1% contamination rate, which means that they store almost every unit they receive. So repositories take a long time to build. [7 years for 13,000 units]

3) StemLife achieved 10,000 units in 2006, about 4 years after operational commencement (I assure you, not without toil).


Another target mentioned by the CEO was 30 transplants for the financial year 2009. I find this to be an interesting target, as I suspect it greatly depend on whether the requests just happen to match the units in the tank? Or perhaps it is now possible to analyze the recipient population and to try to identify the relevant donors to collect the cord blood from.

Anyway, getting back to the financial year for SCBB, I suppose the financial target would be in excess of SGD 1 million in revenue - if they manage to sell the inventory overseas. It is a business after all.


What are the likelihoods of use?

"At least six people are diagnosed daily in Singapore with different types of blood-related diseases said the bank's medical director William Hwang."

"Many of these patients will require a blood stem cell transplant to survive"

"With these samples and those fom banks worldwide, the odds of local patients finding a match is about 10-20%"


OK, quick back of the envelope calculation here. 6 people diagnosed daily in Singapore with a blood related disorder, ie 2000+ people. Let's say 50% will require a transplant at some stage, so let's bring the figure to about 1000 people needing a transplant.

And since only 10-20% will be able to find a match from all available units locally and internationally, ie 100-200 people will get their stem cell treatment... and the rest will have to wait.

The Suze Ormon Show on Cord Blood Stem Cell Banking

I was watching late night TV last year and happened to stumble across the Suze Ormon Show which I had never seen before. Her program entitled "Can I afford it?" discusses the value and worth of any particular item a person, couple or family would like to purchase in the USA.

In this episode, there was a lady who rang up to ask her opinion on cord blood stem cell banking and I thought it would be good to share with StemLife parents. She's quite keen on the subject but I don't think it was sponsored (no brands in sight). Anyway, if you missed it here it is and Suze Ormon is usually on CNBC late in the evening.

Risks involved in receiving treatment with donated fetal neural stem cells: Donor-Derived Brain Tumor Following Neural Stem Cell Transplantation

I find that the PloS Editor's summary in the article itself is an excellent popularized explanation of what the study means so I present it as is (except some added parentheses).

Editor's Summary

Most of the cells in the human body are highly specialized (‘‘differentiated’’). The brain and the spinal cord, for example, contain two main cell types—neurons, which transmit electrical signals to and from the brain, and glial cells, which support and protect the neurons. If these essential neural cells become damaged or diseased, the body cannot replace them. Scientists think, however, that it might be possible to use ‘‘neural stem cell’’ transplants to replace the neural cells that are lost in neurodegenerative diseases (for example, Parkinson’s disease) or damaged by strokes or trauma. Stem cells are undifferentiated cells that replicate indefinitely and that have the potential to develop into many different specialized cells. Pluripotent stem cells (which are able to develop into any kind of specialized cell) can be isolated from early human embryos; ‘‘multipotent’’ stem cells (which develop into only a few cell types) can be isolated from many differentiated tissues, including the brain. Human fetuses (unborn offspring from the end of the 8th week after conception) are thought to be a particularly good source of neural stem cells because many new neural cells are made in fetal brains.

Although stem cell transplantation might provide treatments for many debilitating diseases, some concerns have been raised over its safety (added: especially when unmatched embryonic or fetal stem cells are being used after donation). In particular, some experts fear that tumors might sometimes develop from (added: donated) transplanted stem cells. Tumor cells actually behave very much like stem cells—they divide indefinitely and they tend to be undifferentiated. It is very important, therefore, that every patient who receives a (added: donated, that is a non-self) human stem cell transplant is carefully followed up to see whether any tumors develop as a result. In this study, the researchers describe a case in which multiple, slow-growing, donor-derived brain tumors formed in a patient after the transplantation of (added: donated) human fetal neural stem cells.


What Did the Researchers Do and Find?

Beginning in 2001, (added: donated) fetal neural stem cells were injected several times into the brain and the fluid surrounding it of a boy with ataxia telangiectasia at a Moscow hospital. Ataxia telangiectasia*, a rare disorder characterized by degeneration of the brain region that controls movement and speech, occurs when both copies of the ATM gene (human cells contain two copies of most genes) contain a genetic change that stops the production of functional ATM protein. In 2005, the boy had a magnetic resonance imaging scan at the Sheba Medical Center (Israel) because of recurrent headaches. The scan revealed abnormal growths in his brain and spinal cord. In September 2006, when the boy was 14, the spinal cord growth was surgically removed. This growth has never reappeared but the mass in the boy’s brain has continued to grow slowly. The material removed from the boy’s spinal cord contained both neurons and glial cells, the researchers
report, and resembled a glioneuronal tumor. In addition, it contained both XX (female) and XY (male) cells and the tumor cells had two normal copies of the ATM gene (added: meaning it could not be derived from the recipient since the gene was normal). Finally, a technique called HLA typing showed that the tumor contained cells from at least two donors.


What Do These Findings Mean?

These findings indicate that the growth in the patient’s spinal cord was donor-cell derived and contained cells from two or more donors, at least one of whom was female. Although the growth in the patient’s brain has not been examined, the multiple masses seen in this patient probably arose independently from transplanted cells injected at different sites, suggest the researchers. Importantly, the slow growth of the tumors and the well-differentiated appearance of the cells removed from the patient suggest that the tumors are relatively benign. Donor-derived cells might have been able to establish tumors in this particular patient because people with ataxia telangiectasia often have an impaired immune system and the immune system normally helps to reject tumor cells. Nevertheless, this first example of a donor-derived brain tumor developing after fetal neural cell transplantation is worrying and suggests that further work should be done to assess the safety of this therapy.



This very important study highlights that we know as yet very little about embryonic and fetal stem cells and that their behavior when injected in human tissues is highly unpredictable. Treatments in humans are as yet not advisable but similar uncontrolled experiments are continuously occurring in uncontrolled centers and in desperate situations.

Everyone must be advised, patients and doctors equally that donor embryonic and/or fetal stem cells carry unknown risks. Embryonic and/or fetal stem cell treatment may in the future be a solution to many of today's untreatable diseases but must first be studied in well planned experiments, performed in specialized centers in animal models and must not be ill advised solutions in desperate human patients.


Important for readers to note the difference:

We also need to remember that this is about fetal stem cells obtained from unborn offsprings from the end of the 8th week after conception and not about current approved treatments as bone marrow transplantation using own or matched adult stem cells from cord blood, bone marrow or peripheral blood.



References

1. Amariglio N et al. Donor-Derived Brain Tumor Following Neural Stem Cell Transplantation in an Ataxia Telangiectasia Patient. PloS Medicine 2009; 6(2): e1000029



*More information on Ataxia Telangiectasia from the NIH Neurological Disorders Site

What is Ataxia Telangiectasia?

Ataxia-telangiectasia is a rare, childhood neurological disorder that causes degeneration in the part of the brain that controls motor movements and speech. Its most unusual symptom is an acute sensitivity to ionizing radiation, such as X-rays or gamma-rays. The first signs of the disease, which include delayed development of motor skills, poor balance, and slurred speech, usually occur during the first decade of life. Telangiectasias (tiny, red "spider" veins), which appear in the corners of the eyes or on the surface of the ears and cheeks, are characteristic of the disease, but are not always present and generally do not appear in the first years of life. About 20% of those with A-T develop cancer, most frequently acute lymphocytic leukemia or lymphoma. Many individuals with A-T have a weakened immune system, making them susceptible to recurrent respiratory infections. Other features of the disease may include mild diabetes mellitus, premature graying of the hair, difficulty swallowing, and delayed physical and sexual development. Children with A-T usually have normal or above normal intelligence.


Is there any treatment?

There is no cure for A-T and, currently, no way to slow the progression of the disease. Treatment is symptomatic and supportive. Physical and occupational therapy may help maintain flexibility. Speech therapy may also be needed. Gamma-globulin injections may be given to help supplement a weakened immune system. High-dose vitamin regimens may also be used.


What is the prognosis?

The prognosis for individuals with A-T is poor. Those with the disease usually die in their teens or early 20s.





Read a news account of this story.

The IMPORTANCE of YOUR FAMILY'S STEM CELLS

Haemopoietic stem cell transplantation for children in Australia and New Zealand, 1998–2006:a report on behalf of the Australasian Bone Marrow Transplant Recipient Registry and the Australian and New Zealand Children’s Haematology Oncology Group.

This above study is an important milestone epidemiological study in CHILDREN published in the Medical Journal of Australia in February 2009. It gives us invaluable information and insight on the source of stem cells used (from bone marrow, peripheral blood or cord blood), their origin (autologous: own; related allogeneic: matched siblings; unrelated allogeneic: matched strangers) and on the indications for which a bone marrow transplantation has been performed. Moreover, it studies the important aspect of Transplant Related Mortality (TRM). Few of us actually have insight in those issues and understanding them will aid in deciding whether to keep your own stem cells or not.

Let's have a look!

Over a period of 9 years (1998-2006) 1,259 BMTs were performed in children in Australia and New Zealand, of which 41% were autologous (used the child's own stem cells from bone marrow or peripheral blood) while 59% were allogeneic (someone else's stem cells). Of the latter 40% were from a matched sibling (23.6% of the total) and 60% from matched strangers. That brings the total number of children ultimately finding stem cells from themselves or within their immediate family up to 65% while the remaining 35% had to depend on matched strangers to donate or on donated cord blood. It means that at the end of the day when a child was ill and in need of stem cells for BMT, then those were found in 65% of the cases from the child or the immediate family. More important is that the stem cells used were bone marrow or peripheral blood stem cells and that means that in that perilous period of a family's and a child's life an extra burden in collecting stem cells from the bone marrow or peripheral blood is added on top of all stress that is already evident. One can also speculate how this additional psychological stress and wait may impact on disease progression. If those families had been informed about cord blood stem cells and had kept their children's cord blood stem cells then those little frozen bags would have been stored and waiting to be used at any given time! Furthermore, the importance of using your own or those of a matched immediate relative is reflected in the TRM; Transplant Related Mortality is 22-28% when one receives a matched stranger's stem cells and only 5-7% if one receives their own or a matched sibling's stem cells.

The other important issue is that the matched stranger stem cells come nowadays more from donated cord blood stem cells than bone marrow/peripheral blood. In the latest years more than half, almost 2/3, come from donated cord blood and subsequently since cord blood stem cells are immunologically naïve and cause 30% less rejections, more mismatched transplants have been performed. One can speculate if this is the reason for the difference in Transplant Related Mortality that is higher in mismatched stem cells from strangers. So, if one would not keep for own use one should definitely donate for public use!

In the words of the authors of the study “Autologous BMT has an important role in a range of childhood cancers, including neuroblastoma, medulloblastoma, Ewing sarcoma/PNET, Hodgkin lymphoma and non-Hodgkin lymphoma” while “allogeneic (matched siblings or strangers) transplantation is most frequently offered to children with high-risk and relapsed leukaemias, myelodysplastic syndromes, aplastic anaemia, congenital bone marrow failure syndromes, thalassaemia major, sickle cell anaemia and various inborn errors of metabolism”.

The results of this study are similar to a previous one published in the Biology of Blood and Marrow Transplantation in 2007, entitled “Haematopoietic Stem Cell Transplantation in Australia and New Zealand, 1992-2004”. In this study that encompasses all transplantations in Australia and New Zealand both in adults and children, the same trend is evident and even more pronounced. That is, when you need stem cells you find them in you or in your immediate family! In2004 alone, 68% of the patients used their own stem cells (889/1,313) while another 19% received stem cells from matched siblings and only 13% managed to find stem cells from matched strangers. That means that a total of 87% found the needed stem cells in themselves or within the immediate family! Importantly, Transplant Related Mortality was 8.1% for stem cells from strangers compared 1.1% for own stem cells! One can also in the adult cases speculate how the effect of the additional psychological stress of stem cell collection and/or wait to find stem cells from strangers may impact on disease progression. If those families had kept their own peripheral blood stem cells then those little frozen bags would then have been stored and waiting to be used at any given time!

Cord blood stem cells and peripheral blood stem cells have an immense importance be it for a family's own use or for complete strangers where anyone can offer the hope of life. Regardless the use or the intention, those stem cells must be kept for their purpose to be fulfilled! Do not let them go wasted!

References

1. Moore AS, Shaw PJ, Hallahan AR, Carter TL, Kilo T, Nivison-Smith I, O'Brien TA, 
Tapp H, Teague L, Wilson SR, Tiedemann K. Haemopoietic stem cell transplantation
for children in Australia and New Zealand, 1998-2006: a report on behalf of the
Australasian Bone Marrow Transplant Recipient Registry and the Australian and
New Zealand Children's Haematology Oncology Group. Med J Aust 2009; 190(3): 121-5  

2. Nivison-Smith I, Bradstock KF, Dodds AJ, Hawkins PA, Ma DD, Moore JJ,
Simpson JM, Szer J.Hematopoietic stem cell transplantation in Australia and New Zealand,
1992-2004. Biol Blood Marrow Transplant 2007; 13(8): 905-12