Biomedical Engineering Reference
In-Depth Information
benefit from allogeneic immunotherapy, particularly the elderly and medically
infirm patients with no matched sibling donor [
6,
16
] .
Recipients of allogeneic SC transplant meet with the hazard of GvHD even when
the donor is a sibling who shares the antigens of MHC. Thus, even the perfect HLA
match does not correspond to the best possible genetic match between donors and
recipients. In addition to the HLA complex, other genetic systems operate and affect
the outcome of SC transplant. These include minor histocompatibility systems, as
well as a series of functional polymorphisms in cytokines and chemokines and
receptors genes [
6,
7
] .
Among the events that have essential effect on the result of treatment with SCs
(besides GvHD) the incidence and degree of infectious complications have an
important role. Polymorphisms and/or malfunction of genes controlling the immune
response to pathogens is a critical reason for vulnerability to infection after SC
transplant. These include the HLA class I and class II alleles, Toll and TLR genes,
etc. NK alloreactivity induced by HLA class I epitope mismatching (a common
state in SC transplant) may also be encountered between the donor and the recipient
leading to potentially damaging or advantageous events. Thus, a knowledge of the
role of the most important genetic factors (MHC and non-MHC) will provide the
rationale for a full matching in SC transplant settings [
6,
18
] . ABO-incompatibility
is not a contraindication for SC transplant, but it is an important element for survival
of transplanted cells and development of immediate post-transplant or delayed com-
plications, such as anemia due to immune-mediated hemolysis. Thus, if marrow
aspirate contains incompatible RBCs or plasma, this is an indication for the RBC-
depletion or plasma volume reduction by processing [
18
] . The major RBC-
incompatibility occurs when ABO or other clinically significant antibodies (e.g.,
Kell, Duffy antibodies) in the patient's blood react with donor RBCs. In these situ-
ations, RBCs should be removed from the aspirate. Techniques for RBC-depletion
include HES sedimentation and the use of cell processor or separator. In addition to
RBC-depletion, the majority of transplant programs remove antibodies (typically
anti-A and/or anti-B) from the patient's circulation by plasma exchange.
In a minor ABO-incompatibility, donor's plasma contains antibodies against
ABO antigens that are present on the recipient's RBCs. It usually does not cause
considerable hemolysis, but clinically significant delayed hemolysis can occur in
patients receiving minor ABO-incompatible SCs. Consequently, reduction of the
plasma content in marrow aspirate is required. Plasma can be removed by the cen-
trifugation of the marrow aspirate and removing the plasma layer with a plasma
extractor [
18
] .
ABO-incompatibility and HLA-sensitization (positive cross-match) are the two
main barriers to organ transplants because of the allograft antibody-mediated rejec-
tion (AMR). Nowadays, kidney transplants across immunological barriers are pos-
sible due to existence of highly effective preconditioning protocols (regimens)
[
19-
22
]. Pretransplant regimens in ABO-incompatible kidney transplant setting
include anti-CD20 infusion, therapeutic plasma exchange (TPE), extracorporeal
immunoadsorption (ECIA), and standard triple immunosuppression: tacrolimus/
mycophenolate-mofetil/steroid [
19,
20
]. The weak-point of “conventional” TPE is
