Below are additional follow-up questions asked by attendees during the
All answers have been graciously provided by our expert panel of speakers:
Additional responses from speakers will be posted as soon as they are available.
In order of presentations made on November 15th, 2018
Questions for Dr. Joanne Kurtzberg
How do you overcome a TC's fear when they have had a bad outcome after CBT?
- TCs should review the literature about long term outcomes after CBT. They will learn that they are favourable and frequently better than those after transplants with BM or PBSC stem cell sources. They should also collaborate with experienced centers to learn how to best select a CB donor and also provide supportive car in the early post-transplant period.
- I don’t know enough about placental encapsulation to fully respond to this question. However, I do not think removal of the cord blood should interfere with this process.
- The causes of autism are not completely understood. Approximately 3-10% of patients have mutations in their DNA which are responsible for the disease. These mutations can be detected by testing of blood or other cells through testing that includes fragile X, Rett syndrome, chromosomal microarray and whole exome or whole genome sequencing.
- We are testing whether cord blood infusions are beneficial for children with autism. We do not yet know whether cord blood infusion helps. If it does help, we hope to identify the characteristics of the children who will best respond to the therapy.
- We don’t know yet. The data is being analysed soon.
- We are defining the final eligibility now. It will likely include children ages 4-8 years and start late spring or early summer of 2019.
- Much of the rationale of delayed clamping is not evidence based, particularly in term infants. It has been shown that delaying clamping for up to 60 seconds does not significantly impact the volume of cord blood that can be collected. We are hoping that centers that support cord blood collection will limit delayed clamping to 60 seconds.
- Approximately 35% of samples did not meet the eligibility requirements.
- We thaw cord blood in an automated device called the Sepax RM. During the thaw the cells are combined with dextran 40 and human serum albumin to prevent lysis of cells as they warm in the presence of DMSO. The cells thawed, washed and concentrated to a volume that is appropriate for infusion into the patient based on the patient’s weight. Thawed cells are also tested for sterility, viability, total nucleated cell count recovery, viable CD34 content and growth of colony forming units.
- The CD14 cells are a type of monocyte. This type of cell has not always been quantitated by cord blood banks. So right now, consumers cannot ask for or expect this information from banked cord blood.
- Probably 3-5 years.
- No. Cord blood infusions without chemotherapy or immunsuppressing therapy do not cause this problem.
- Yes, anecdotally, some kids with speech apraxia do improve by speaking more after cord blood infusion. However, this has not been studied in a formal clinical trial.
- We don’t know.
Questions for Josefine Neuweiserhuiser-Teeler
Is there any difference in the cost for cord units depending on the country of origin? And is this a factor when choosing the best one for transplant?
- Yes, there is a quite big difference in costs for different CBU's, in general this is taken into account if CBU's are similar in match grade/cell dose, but in general a CBU that is of much less quality will not be chosen.
- In general units with a viability below ~40-50%, will not be used (especially if the viability is that of CD34+ cells). With such a low viability the CFU is also taken into account and if the CFU is good, they might reconsider. One could also think that if no other units are available and the cell dose of the unit is very large (say the patient is a child of up to 10kg) one might consider using the unit in this case as the remaining cell dose would still be enough for this patient.
- In the Netherlands CFU is usually only taken into account if the viability is low, and in that case a CFU of >0.5*10^5 total CFU/kg might be used
- Both Netcord/Fact and AABB accredited banks would be good options, in general accredited banks will have better monitored processes in place than non-accredited banks. In the article by Purtill et all from 2014 in Blood “Dominant unit CD34+ cell dose predicts engraftment after double-unit cord blood transplantation and is influenced by cord blood bank practice” Netcord/Fact accreditation is mentioned as having a positive effect on the outcome. The reasoning why this has a positive effect on the outcome can also be translated to AABB (several comparisons have been made between AABB and Netcord/Fact standards, these comparisons suggest they are similar in many respects though AABB is broader than only for CB banking).
- CBUs stored for 20-25 year still seem in good condition, so it doesn't seem like they deteriorate with time. But what is known is that banking practices have very much approved in more recent years. So, if you consider this than a more youthful unit could be a better choice if available.
Questions for Dr. Juliet Barker
Questions for Lyla Edgington & her family
Lyla is such a beautiful little girl and so fortunate to have found treatment thanks to cord blood. In more classic transplants, there can be side effects. Have you/she noticed any side effects following the CB transplant? If so, are these temporary?
- Thank you so much! Lyla has annual testing done for post transplant side effects and so far she doesn’t have any related to the cord blood transplant (No GVHD, blood pressure is normal now, kidneys are good, etc). The only significant effect is we were told she will be infertile due to the chemo regime before transplant.
- Nothing that we can think of. We were so fortunate to have a nearly perfect transplant process.
- Yes, we had United Healthcare and they were very understanding and pretty helpful. Lyla’s disease (and treatment) fell under a list in which her transplant and hospital stay was covered at 100%, no questions asked. However, it was a part-time job for me to review all hospital invoices and insurance codes/payment amounts! I found several mistakes but luckily they were all fixed in a timely manner.
Questions for Dave Murphy & Monroe Burgess
Does the shipping process differ depending on whether the cord blood bank is accredited or not? Example: A bank not accredited by AABB, FACT or similar versus one that is accredited.
- The shipping process is the same for all cord blood banks, with the mission of preserving the integrity of the cord blood cells in transit. Each cord blood bank may vary in their requirements, such as communication protocols and packaging, and we incorporate their specifications into our customer-specific standard operating procedures. In addition, there are specific regulatory guidelines relating to these shipments that must always be adhered to, in order to be compliant.
- The shipping process is the same for all cord blood banks, whether private or public, with the mission of preserving the integrity of the cord blood and cells in transit. Each cord blood bank may vary in their requirements, such as communication protocols and packaging, and we incorporate their specifications into our customer-specific standard operating procedures. In addition, there are specific regulatory guidelines relating to these shipments that must always be adhered to, in order to be compliant.
- There are certain commodities that are exempt for the X-ray screening method. Cord Blood is one of those exempt commodities. However, these shipments may be screened by alternative means. As an example, the TSA may use swab analysis or even a security “sniffer” dog. Since Quick is a TSA screening facility, the majority of our packages do not go through additional screening, however, there could be instances of random screenings for security measures beyond our control.
- The requirements for shipping cord blood for transplant or research are the same. Depending on the type of research being conducted and how the cord blood is being used, will determine the shipping conditions. As an example, many products are shipped at various temperatures. They could ship ambient, controlled room temperature or frozen. This would not have any impact on the shipping transit time or logistics.
- With the use cord blood cells becoming more widespread in the potential use of regenerative medicine and other disease therapies, we expect to and are prepared to handle a much higher volume of cord blood shipment worldwide. We recently opened a Cell and Gene Therapy Center of Excellence in the US to accommodate the higher volumes. We also are seeing an increased awareness in the importance of transportation and logistics in the supply chain by stakeholders. In addition, the regulatory landscape may continue changing, which will have effects on the supply chain processes and protocols
- We provide educational content to help spread awareness of life saving cord blood, which is published on our website www.quickhealthcare.aero, and social media. Our recently published eBook on cord blood banking is also recommended: download eBook here. We speak at industry forums and work in collaboration with industry organizations, such as Save The Cord Foundation and World Cord Blood Day, to help educate the public and medical community. In addition to promoting the possibilities of cord blood cells in medicine, we also discuss best practices in the transport of cord blood throughout the supply chain.
Questions for Dr. Charles Cox, Jr.
Can you talk about your supply chain to get cord blood within the required time?
- There are two answers to that question: (a) For acute studies, we use our own cGMP facility to process hUCB, ensure release criteria are met, store the cells/aliquot them for dosing, and deliver them for clinical use. (b) For chronic studies, it is very similar to BMT release from a private or public bank.
- Unfortunately, for our acute studies using UCB, we aren’t using banked blood, rather we are using an acutely collected, autologous unit.
- In terms of our neuroprotection trial for congenital diaphragmatic hernia, the patient typically has the diagnosis of CDH made in utero by ultrasound. I would recommend contacting our clinical coordinator (available on ClinicalTrials.gov). Then, we could determine eligibility and the logistics of enrolling in the trial.
- Really, for non-homologous use of a therapeutic, things haven’t changed all that much. I think it can become open to interpretation what is “homologous” activity of a cell intrinsically, and people make various arguments about that.
- My advice regarding donation is to consider private banking if it reasonably falls into your household budget. I would encourage it for potential near-term uses if there are risks or clinical trials exist for a diagnosis or disease that is anticipated for your child. If one is considering donating to a public bank, do a little research to ensure they are financially sound so that the unit will be available in the long term.
Questions for Susana Cantero Peral
How far away is this stem cell treatment from FDA approval?
- Currently we are finishing the Phase I clinical trial, and within one month the Phase 2 will be initiated.
- We collect cord blood from any place of USA mainland. A courier company is contacted right after the cord blood has been collected and they bring the cord blood to the manufacturing site for its processing. We have just had a couple of occasions where we have exceeded the 36 hours because of natural disasters. The viability of the cells was in range.
- That is right. Cord blood has been used to treat mainly hematopoietic disease since the last 25 years. However in the last years it has been used in several clinical trials in medicine regenerative with promising results. UCB stem cells are biologically closer to embryonic stem cells, offer improved plasticity and faster growth rates. Furthermore, we based this study on the hypothesis that injection of UCB cells in patients with congenital heart disease do not need to durably engraft but rather, to circulate and temporarily survive for sufficient time to alter the paracrine signaling of endogenous cells, and make the right side of the heart stronger.
- It is known that late sequelae of suboptimal cardiac performance of babies affected of HLHS contribute to heart and multi-organ dysfunction including detrimental effects on lungs, kidneys, liver and brain. Development of therapeutic strategies to improve single ventricular function, such as stem cell therapy, could improve or prevent those complications. We have compared the characteristics of CB from HLHS and healthy babies, and no differences have been seen.
- Currently, we are expanding the cord blood collection from HLHS babies outside of the USA. We have collected from Canada in one occasion and from Europe in a couple of times in the last week. So, yes, it could be a possibility to recruit patients from outside of the USA, such as Montreal.
- We strictly follow the FDA regulations because it is the only and correct way to conduct a clinical trial. In our case, since we are working with a pediatric population where the cells are injected into the heart, the regulations are even stricter. In order to launch the current clinical trial we had to carry out a pre-clinical study with large animals mimicking the clinical trial, so autologous cord blood from every animal was collected, processed and injected back following the same cell release criteria established in the clinical protocol. Unfortunately, there are so many clinics where they use stem cells in a huge variety of diseases, claiming their benefit without being regulated or even being tested previously in a clinical trial.