Blood cancer: Is cord blood a better therapy than bone marrow?

cord blood cells

A leading expert in the field has argued that cord blood may have advantages over the use of unrelated donor bone marrow in transplants in patients with blood cancers.

Chairing a session about cord blood transplantation at the Transplantation and Cellular Therapy (TCT) 2019 conference, Juliet N. Barker, MD, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, and Department of Medicine, Weill Cornell Medical College, New York City, said she is confident that the use of cord blood for transplantation in patients with hematologic malignancies will increase in the coming years.

Dr Barker explained “there’s a huge amount of research going on” which will “demonstrate that it is a very useful stem cell source both for basic clinical transplantation as well as, for example, cellular therapy and regenerative medicine applications.”

Among the new data presented at the conference were studies showing reduced relapse and chronic graft versus host disease (GVHD) rates seen with cord blood versus other approaches, which could lead to cost savings down the line.

Multiple studies have also shown that the relapse rate in patients with minimal-residual disease is lower after cord blood grafting than when using HLA-matched or mismatched unrelated donors.

In addition, several studies showed that, with the right techniques, cord blood can achieve early results at least as good as, for example, unrelated donor (URD) transplants, and good results in the elderly.

Moreover, cord blood has huge advantages over other sources of HTCs, as it is available to patients from a much wider ethnic heritage and can be prepared for use extremely quickly.

Issues With Cord Blood Transplants

Despite these advantages, the use of umbilical cord blood as a source of hematopoietic stem cells (HTCs or HSCs) for transplants for patients with blood cancers has declined in recent years in the United States.

Dr Barker gave a number of reasons for this decline: unit selection is more complicated than for URD or haploidentical transplants, and the cord blood units have a higher cost and are associated with longer hospital stays.

Barker also noted that cord blood transplants are seen as a “last ditch” therapy and that the increase in ex vivo expansion before transplantation to achieve quicker hematopoietic recovery has been at the expense of the use of cord blood without expansion.

To reverse the decline in cord blood transplants, she said that the efficiency of cord blood searches needs to be improved, alongside cord blood inventories and unit selection.

It also needs to be made easier to perform cord blood transplants, which will require new technologies and novel clinical trials and collaborations.

While all of those steps are already underway, Barker said reducing the unit cost of cord blood would be advantageous, as would demonstrating cost-effectiveness by showing that the initial costs are offset by the long-term benefits.

Cord blood expansion

Barker believes cord blood expansion could provide the answer to the challenges facing cord blood stem cell use in the US.

She said the requirements for success for a cord blood expansion technology are that it be: logistically easy; have a high likelihood of improving myeloid recovery; and is cost-effective.

Although there are several technologies for cord blood expansion, she pointed out that none have yet fulfilled all the requirements for success.

Last year, Shaun Mansfield, Biovault Technical Ltd and UCL Ph.D. Academic, was awarded an Industrial Fellowship by The Royal Commission for the Exhibition of 1851 for his project: Improving stem cell yield from umbilical cord blood to drastically improve blood-based cancer and novel emerging treatments.

Prince Albert’s educational legacy offers support of up to £80,000 to the UK’s 14 most promising young doctoral engineers and scientists. Shaun’s research aims to improve the yield of stem blood cells from umbilical cord blood to improve the treatment of blood-based cancers.

Cord blood stem cells are now used routinely to treat over 80 diseases of the blood and umbilical cord. The youth and vigour of cord blood stem cells make them an especially powerful and adaptable therapeutic resource.

However, they are limited in number, with each cord blood sample typically containing enough stem cells to treat a young child. Transplant nurses currently use two or more samples (a double cord blood transplant) to treat older children and adults suffering from diseases such as leukaemia and sickle cell disease. Shaun’s research will enhance our understanding of cord blood stem cells and seeks to develop methods to improve yields, and patient outcomes.

To reduce treatment-related mortality without cord blood expansion, Barker suggested that this could be achieved with more efficient unit searches and better selection of units.

Another approach is to perform double-unit cord blood transplants (dCBTs). Barker pointed to research by Ioannis Politikos, MD, Memorial Sloan Kettering Cancer Center, New York City, presented here in Houston on that topic, adding that these results show that double-unit grafts can be used to “safely transplant mismatched units in adults.”

Problems with other HSC sources

Barker emphasized that other sources of HTCs are not without their problems.

One of the major limitations of URD transplants is that, unless the patient is of northwestern or Eastern European heritage, it is likely that finding a donor will be difficult.

She said that individuals with Southern European, Asian, White Hispanic, African, and other heritages do not generally have an 8/8 unrelated donor, and the situation “is not improving.”

This is because the US population is becoming more diverse, with donors aged younger than 35 years less likely to match patients of any age because of having a unique human leukocyte antigen (HLA) profile.

Moreover, not everyone has a haploidentical donor, with, again, individuals of African descent significantly less likely to have a haploidentical graft available than those of European descent.

Haploidentical transplants are also limited by the requirement that donors have to be medically, socially, and psychologically fit to donate, as well as the need to workup multiple haploidentical donors in case there is an issue with the donors. In addition, there is a lack of pediatric and older donors.

Barker pointed out that the prevention or treatment of relapse after allograft may not always work, especially if the patient is in full-blown relapse.

All this, Barker said, “makes the cord blood inventory very important.”

Sources

Cord Blood Instead of Bone Marrow for HSCT for Blood Cancers, Liam Davenport, February 21, 2019

2019 TCT Transplantation. Presented 20 February. Poster 312

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