Transplantation: general information

Transplantation may be performed using the patient's own tissues (autotransplantation; e.g., bone, skin graft), genetically identical (syngeneic) donor tissues (isotransplantation), genetically different donor tissues (allo- or homotransplantation), and sometimes using grafts taken from other animal species (xeno- or heterotransplantation). Grafts may be single cells [such as hematopoietic stem cells (HSC), lymphocytes, pancreatic islet cells], parts or segments of organs (liver or lung lobes, skin grafts), or entire organs (heart).

Structures may be transplanted into their usual anatomical location (orthotopic transplantation, such as heart transplantation) or into an unusual location (heterotopic transplantation, such as iliac kidney transplantation). Transplantation is almost always performed to improve survival. However, some procedures (hand, larynx, tongue, face transplantation) improve quality of life but reduce life expectancy and are therefore controversial.

Except in rare cases, clinical transplantation uses allografts from living relatives, unrelated donors, and cadaveric donors. The most common organs harvested from living donors are kidneys, HSCs, liver segments, pancreas, and lungs. The use of organs from cadaveric donors (with or without a beating heart) helps reduce the mismatch between organ demand and availability; however, demand still greatly exceeds resources, and the number of patients awaiting transplantation continues to grow.

Distribution of organs

Organ allocation is based on the severity of damage to certain organs (liver, heart) and the severity of the disease, time on the waiting list, or both (kidneys, lungs, intestines). In the United States and Puerto Rico, organs are allocated first to 12 geographic regions, then to local organ procurement organizations. If there are no suitable recipients in one region, organs are redistributed to recipients in other regions.

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The main principles of transplantation

All recipients of allografts are at risk of rejection; the recipient's immune system recognizes the graft as foreign and attempts to destroy it. Recipients with grafts containing immune cells are at risk of developing graft-versus-host disease. The risk of these complications is minimized by pretransplant testing and immunosuppressive therapy during and after transplantation.

Pre-transplant screening

Pretransplant screening involves testing recipients and donors for HLA (human leukocyte antigen) and ABO antigens, and in recipients, sensitivity to donor antigens is also determined. HLA tissue typing is most important in kidney transplants and the most common diseases requiring HSC transplantation. Heart, liver, pancreas, and lung transplants are usually performed rapidly, often before HLA tissue typing is complete, so the value of pretransplant screening for these organs is less well established.

HLA tissue typing of peripheral blood lymphocytes and lymph nodes is used to select an organ based on the most important known determinants of histocompatibility between donor and recipient. More than 1250 alleles define 6 HLA antigens (HLA-A, -B, -C, -DP, -DQ, -DR), thus organ selection is a complex task; thus, in the USA, on average, only 2 of 6 antigens match between donor and recipient in kidney transplantation. Selection of an organ with the largest possible number of matching HLA antigens significantly improves the functional survival of a kidney graft from a living relative and donor HSCs; successful matching of a graft based on HLA antigens from an unrelated donor also improves its survival, but to a lesser extent due to multiple undetectable differences in histocompatibility. Improvements in immunosuppressive therapy have made it possible to significantly improve transplantation outcomes; HLA antigen mismatch no longer precludes patients from receiving transplants.

Matching of HLA and ABO antigens is important for graft survival. Mismatching of ABO antigens may cause acute rejection of well-perfused grafts (kidneys, hearts) that have ABO antigens on the cell surface. Previous sensitization to HLA and ABO antigens results from previous blood transfusions, transplantations, or pregnancies and can be detected by serologic tests or, more commonly, by lymphocytotoxic tests using recipient serum and donor lymphocytes in the presence of complement components. A positive cross-match indicates that the recipient serum contains antibodies directed against donor ABO or HLA class I antigens; this is an absolute contraindication for transplantation, except in infants (under 14 months of age) who have not yet produced isohemagglutinins. High-dose intravenous immunoglobulin has been used to suppress antigens and facilitate transplantation, but long-term results are unknown. A negative cross-match does not guarantee safety; when ABO antigens are comparable but not identical (e.g., type O donor and type A, B, or AB recipient), hemolysis may occur due to production of antibodies to transplanted donor lymphocytes.

HLA and ABO typing improves graft survival, but dark-skinned patients are at a disadvantage because they differ from white donors in HLA polymorphism, higher frequency of presensitization to HLA antigens, and blood groups (0 and B). To reduce the risk of infection, possible contact with infectious pathogens and active infection must be excluded before transplantation. This includes history taking, serologic testing for cytomegalovirus, Epstein-Barr virus, herpes simplex virus, varicella-zoster virus, hepatitis B and C viruses, HIV, and tuberculin skin tests. Positive results require posttransplant antiviral therapy (e.g., for cytomegalovirus infection or hepatitis B) or refusal of transplantation (e.g., if HIV is detected).