Biomedical Engineering Reference
In-Depth Information
HLA compatibility is required for engraftment and to prevent GvHD, regardless of
immunosuppressive treatment of recipient. Both the recipient and the potential
donor have to be tested for HLA-A, -B, -C, -DR, and -DQ antigens. The aim is exact
matching of the HLA-A, -B, and -DR antigens. DNA typing is carried out on sam-
ples from both the donor and recipient for best evaluation of HLA class I and II
compatibility. Although HLA-identical sibling donors stay the best choice and the
most frequent for SC transplant, there are expanding requests and use of unrelated
donors. In addition, a cross-match of recipient serum against donor lymphocytes is
required. The positive result of cross-match with unfractionated lymphocytes or
T lymphocytes is a contraindication to transplant [
13-
15
] .
HLA typing for HLA-A and HLA-B has typically been dependent on serologic
methods. However, GvHD and engraft failures are due to phenotypically matched
unrelated donors with considerable differences in alloantigens not identified by
serologic techniques. Due to the heterogeneity of the class I antigens, serologic
techniques are in practice for HLA-A and HLA-B typing in many centers, but
molecular typing is being performed with increasing frequency, particularly in unre-
lated transplants. Mismatching for a single class I or II alleles increases mortality
rate. The class I HLA-C antigens have possibly a less important role in the T-cell
immune response because of their reduced polymorphism and low expression on
the cell surfaces. However, it is generally accepted that HLA-C antigens can be
identified by cytotoxic T lymphocytes and NK cells, which may be associated with
an increased hazard of graft failure. In contrast, the risk of GvHD is greater with
HLA class II disparity. Testing for HLA-DR and HLA-DQ is regularly performed
by molecular technology, i.e., DNA-based technique. This method gives better reso-
lution (including subtypes of these alleles) than conventional serologic technique.
Recent studies have demonstrated the importance of recipient HLA-DRB1 and
HLA-DQB1 allele disparity in the development of GvHD [
6
] .
Finally, the HLA null alleles are characterized by the absence of a serologically
detectable gene product. Since serological HLA diagnostics are progressively
replaced by DNA-based typing methods considering only small regions of the
genes, null alleles may be misdiagnosed as normally expressed variants. The failure
to identify an HLA null allele as a non-expressed variant in the SC transplant setting
may result in an HLA mismatch that is highly likely to stimulate allogeneic T cells
and to trigger GvHD. Since the occurrence of HLA null alleles is around 0.3% or
even higher, a screening strategy for HLA null alleles should be implemented in the
clinical laboratory. It may consist of the combination of serology and standard
molecular typing techniques [
17
] .
Umbilical cord blood (UCB) has recently been discovered as an alternative SC
source for allogeneic cell therapy in both adults and pediatric patients with hemato-
logical malignancies and marrow failure syndromes. The relative ease of procure-
ment, tolerance of 1-2 antigen HLA mismatch, and lower than anticipated risk of
severe GvHD have made UCB an attractive alternative to marrow-derived SCs.
Given that adults are larger than children, there was still limited enthusiasm for the
use of UCB in adults. The use of reduced-intensity or non-myeloablative prepara-
tive regimens to allow engraftment of UCB broadens the scope of patients who may
