Review of information leading to above conclusions:

Transplant physicians may choose not to use a cord blood unit that is positive for anti-HBc ("core-positive") because of an inaccurate understanding of the risk. If a unit in question is clearly the optimal unit for a transplant because of high cell dose and good HLA-matching, the risk of using a second best unit may be greater that the risk of using the core-positive unit. Although one should not assume that the risk of using a core-positive unit is zero, the available data suggest that the risk is small. The following data are available to assess the risk.

Three large U.S. studies have been performed to determine the percentage of blood donor units that are anti-HBc-positive but otherwise negative in infectious disease testing that may transmit hepatitis B virus (HBV). The studies determined the percentage of units with detectable amounts of HBV DNA as detected using molecular techniques.

The three studies were performed by the Retrovirus Epidemiology Donor Study (REDS) Group (1), American Red Cross (ARC) (2) and as part of the Roche Ampliscreen HBV clinical trial (3). These studies indicated that 0.24% to 0.63% of core-positive units are positive for HBV DNA. The number of samples tested in the studies was 395, 3000 and 3,956, respectively. The references are indicated below, and all of these studies are reviewed in the reference by Busch (3).

There are data to indicate that HBV DNA positive samples can transmit hepatitis B, so that it is prudent to assume that all such units are infectious, even though the viral load is often so small that they may, in fact, not transmit the infection. It is also relevant to point out that the risk of transmission of hepatitis from a core-positive unit depends on the viral load/mL and the number of mL infused. Those units that are only positive for anti-HBc in infectious disease testing, but that are also positive for HBV DNA almost always have a low viral load. Further, the volume of plasma infused as part of a cord blood product is small. Accordingly, the use of a cord blood that is core positive is not analogous to transfusion of a unit of plasma or RBCs. It is not clear that cord bloods with such a low viral load would transmit hepatitis.

Using a core-positive unit does not conflict with FDA Guidance documents. According to the FDA Guidance for Industry, "Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)", May 2004. There is an exception for cord blood collection and storage which states: "When the maternal sample tests negative for HBsAg and reactive for core antibody, cord blood units may be collected and stored in quarantine. Use of these cord blood units, if there is no comparable cord blood unit for the recipient, is not prohibited in cases of urgent medical need (§1271.65(b))."

Since the probability of a core-positive unit containing HBV DNA is only 0.24 - 0.63%, transplant physicians may judge that the use of a core-positive unit provides less risk to the patient than the use of a second best unit which may be less well HLA-matched and/or have fewer nucleated cells. Also, transplant physicians may obtain further information by performing a test for HBV-DNA on a maternal sample when the cord blood is core-positive. Such testing is available but is not licensed by the FDA.