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Stem Cell Transplants with Cord Blood
Sun, JJ et al., Transfusion Sept. 2010; 50(9):1980-1987
The two important measures of patient outcome are: long-term survival, and the impact on quality of life from graft-versus-host disease (GvHD). Sibling donors tend to trigger less GvHD. Also, sibling donors are available faster than searching for an unrelated donor, and patients have better survival when they go to transplant faster after diagnosis.
The exact comparison of outcome between sibling or unrelated donor varies with the patient diagnosis. The NMDP website has a page on this, with numerous references. For many cancers the outcomes are comparable, although sibling donors have a slight edge. The largest study was by Weisdorf et al. 2002, for over 2900 patients with CML leukemia. When correcting for all other factors, the survival with sibling donor vs unrelated donor was 68% vs. 61%. Sibling donors show a significant improvement for pediatric cord blood transplants of hereditary disorders. The European Blood and Marrow Transplantation Group (EBMT) reported 3 year survival rates of 95% from a sibling donor vs. 61% from an unrelated donor.
Weisdorf, D.J. et al. Blood 2002; 99:1971-1977.
Bizzetto, R. et al. (EBMT) Haematologica 2011; 96(01):134-141
1.3 mL of cord blood for every pound of patient weight, -or-
2.9 mL of cord blood for every kg of patient weight
However, as more transplant centers are adopting the practice of giving adult patients "double cord blood transplants" with two cord blood units, it is less critical for both units to have adequate cell dose.
Reed, W et al., Blood 2003;101(1):351
Barker, JN et al., Blood 2005;105:1343-1347
Eapen, M et al. Lancet 2007;369:1947-54
Rocha & Gluckman Brit. J. Haematology 2008;147:262-274
Delaney, C et al., Brit. J. Haematology 2009;147:207-216
Michallet et al. 2010 Blood 2010;116:Abstract#361
Briefly, there are 6 HLA types that are important for stem cell transplants: in a bone marrow transplant the patient and donor must match at all 6 (100% match), whereas a cord blood transplant is just as effective at curing patients with only a 4 out of 6 match (67% match) between donor and patient. This is the reason that donations to the national cord blood inventory managed by NMDP are so important to help patients who come from minority or mixed ethnic backgrounds.
The HLA type of cord blood is always measured by public banks, and then the type is listed on a registry that can be searched by patients seeking a transplant. Family banks typically do not measure the HLA type at the time of banking, because it is an expensive lab test and and can always be checked later from a testing segment of the stored cells.
Stem cells happen to be Mono-Nuclear Cells or MNC: when you look at them under a microscope there is only one nucleus. Unfortunately, one of the most difficult aspects of stem cell biology is that you can't identify a stem cell just by looking at it. There are other types of blood cells which are also MNC, such as nucleated red blood cells. The only proof that a cell is a stem cell comes from how it behaves when it multiplies.
Scientists have worked for years to develop various chemical stains which have a high affinity for stem cells. The best known marker for blood-forming stem cells is that they test positive for CD34, a protein found on the surface of stem cells. But, CD34+ counts are not an accurate measure of stem cells: CD34+ results vary between labs, they can vary within a single lab, and only 1-2% of the MNC that have CD34+ are actually stem cells.
The Total Nucleated Cell count or TNC is the test most often reported as a measure of the cell count after cord blood processing. The main advantage of measuring TNC is that the count is highly reproducible within and among labs, so it can be used accurately throughout the blood banking community. Even better, the TNC count can be automated with the use of a device called a flow cytometer.
At present Colony Forming Units or CFU are considered to be the best measure of whether stem cells are "viable", or quite frankly alive. The TNC count includes both living and dead cells. In the CFU test a small portion is watched under controlled conditions to see if stem cells divide and form colonies. This used to be a subjective measure, but recently it has been standardized with technology to image the cells and count colonies in the image. The only remaining problem with the test is that it takes days for colonies to grow.