Brunstein's "Umbilical cord blood transplantation and banking" 2006
From Biol557
Contents |
[edit] Abstract
- They will review the state of the art and new techniques designed to increase the recipient base and to make transplants more effective.
[edit] Introduction
- Though bone marrow transplants are the standard of care for several diseases, 50-60% of patients that need a transplant will not find a matching HLA donor. This percentage increases if the patient is a minority.
- Cord blood is awesome because there is no risk to the donor, it is enriched in hematopoietic progenitor cells compared to bone marrow and peripheral blood, it can be transplanted between unmatched donors and patients, and it can be transplanted with little risk of disease transmission.
- There are three limitations to cord blood transplants (UCBTs) however:
- The ratio of donated cells to host cells is important for success and since the number of cells in a single cord blood sample is fixed, adult patients are usually denied access because their ratio will be higher and thus there is a decreased potential for success.
- Second, unlike bone marrow transplants, one cannot go back to the donor and ask for more of the same (that is, HSCs).
- There is much less experience with transplanting cord blood than with transplanting bone marrow.
[edit] UCBT in children
- The first transplants were in the early '90s.
- Now thousands have been done.
- Experience shows that HLA mismatch is acceptable as long as 4 of 6 HLA antigens are matched.
- Immune / blood system reconstitution takes a little longer with UCBT as compared to BMT (bone marrow transplants).
- Researchers are working on a way to increase the rate at which each cell type is reconstituted.
- They measure the levels of platelets, white blood cells, etc.
- There is evidence that grafts work best when total body irradiation is used.
- UCBT is shown to allow acute graft-versus-host disease less frequently than BMT.
- There is disagreement on whether or not UCBT decreases lifelong GVHD.
- Researchers have calculated a critical dose (1.7 × 105 CD34/kg), under which, patients have a very high treatment-related mortality rate.
- Relapse rates are lower in UCBT patients than in BMT patients.
- HLA matching and higher cell dose (that is ratio of donated cells to host cells) increase survival rates.
[edit] UCBT in adults
- Because of the clinical threshold for success, there are few (25%) of adult patients that are eligible for UCBT.
- There seem to be two methods of transplantation: cryopreserved and infused.
What is the difference between these two methods?
- In adults, we see the same, slower reconstitution with UCBT as compared to BMT.
- Adults show less acute GVHD with UCBT than with BMT, same as children.
- Adults show increased long-term GVHD with UCBT as compared with BMT, however.
- There is confusion about the mortality of adult UCBT compared to BMT because of patient disease severity differences.
- As with children, relapse rates were lower for adults receiving UCBT as compared to BMT.
- "Survival is influenced by recipient age, disease status, recipient cytomegalovirus (CMV) serostatus, and UCB graft nucleated cell dose."
[edit] Multiple umbilical cord blood units
- Using two UCB units has been shown to work in adults / large adolescents.
- The mixture and administration of two mismatched units has been done, too, and shown variable results.
- They showed that chimerism was displayed in the blood cells in all patients (as expected) but by day 100, only one population of the two transplanted was responsible for making blood cells.
- Using two units increases survival and decreases treatment related mortality (TRM).
[edit] Nonmyeloablative Umbilical Cord Blood Transplantation
- Because ablation (which is usually done before transplants to kill off the host bone marrow) is part of the issue with GVH, we wanted to try transplanting without first ablating.
- This kind of transplant seems to show higher acute GVHD but maintains low TRM and low long-term GVHD.
[edit] Future directions
- We're getting pretty good at this, but many places that do stem cell transplants have not started UCBTs.
- We need more data to speak specifically about it's potential for a given disease.
- Phase II studies are being published but will need to be replicated.
- One challenge is finding enough UCB to work for adults.
- We may be able to make UCBTs work better if we combine regulatory T cells and / or peripheral blood stem cells (PBSCs).
[edit] T regulatory (Treg) cells
- Using Treg cells with transplantation can decrease acute GVHD and promote high levels of donor chimerism.
[edit] Ex vivo expansion culture
- This is the idea that expanding a culture of CB stem cells and then infusing them might make them better.
- They designed their experiments pretty poorly, so now they are doing new experiments.
[edit] Intra-bone marrow injection
- Less than 20% of HSCs injected intraveneously end up in the bone marrow, which is bad, so we're looking for ways to make homing better.
- Only one study has been published.
- This is important because we don't have much cord blood, so we have to make it count.
[edit] Mesenchymal stem cells
- MSCs help transplanted CB stem cells engraft.
- MSCs are partially regulated by Treg cells.
- One study has been done where they add MSCs with a UCBT, but more trials must be done to calculate significance.
[edit] Cord blood banking
- There are at least 15 blood banks in the US that collect UCB.
- Several groups, including the FDA, have produced guidelines for collecting, maintaining, and documenting UCB.
- The authors (from MN, one of the largest blood banks and UCBT centers) reviewed blood from the 14 other blood banks and found some issues
- They found:
- examples of samples sent as "suitable for transplant" when they had disease test incomplete or even positive.
- samples that had not been tested for bacterial or viral infections.
- issues relating to shipping.
[edit] Summary
- UCBT is becoming the standard of care and, in the pediatric scene, will soon overtake BMT in rate of performance.
- Adult UCBT is moving more slowly because of the need for double doses.
- Work on making a single dose more potent (by increasing homing or engraftment) continues.
- Using nonablative pre-treatment for the transplant broadens the procedure candidacy.
- We're still looking for more ways to make recovery faster and better.
- Expanding CBB (cord blood banks) and making sure that proper guidelines are being followed are both essential goals to furthering the field and the therapy.
