Transplantation

Last updated: May 9, 2022

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Transplantation is the process of transferring an organ or part of an organ (known as a graft) from one donor to either him/herself (autologous transplantation) or another recipient (allogeneic transplantation) or their genetically identical recipient (isograft transplantation). In addition to being subject to strict legal requirements, the donor and recipient must be histocompatible in allogeneic transplantations to minimize the risk of transplant rejection. Because the major histocompatibility complex (MHC) is only perfectly matched in isotransplantation (involving the transfer of genetically identical tissue, e.g., between identical twins), allogeneic transplantation subsequently requires immunosuppressive therapy.

Transplant immunology

Major histocompatibility complex (MHC) and human leukocyte antigen (HLA)

See “Major histocompatibility complex” for more details.

Allorecognition

Prerequisites for organ matching

Cross-matching (transplantation)

ABO compatibility

Rh compatibility is not required for solid organ transplantation. Both Rh compatibility and ABO compatibility are not essential for hematopoietic stem cell transplantation.

Histocompatibility

  • Principle
  • Coding of mismatch degree (HLA-DR, HLA-A, and HLA-B)
    • 0: no mismatch
    • 1: mismatch on either the paternal or maternal chromosome
    • 2: mismatch on both the paternal and maternal chromosome
    • 000: a complete match
    • 222: a complete mismatch
  • Odds of histocompatibility
    • For a sibling, the probability that the patient has an HLA compatible sibling is 1 - (0.75)n (where n is the number of siblings).
    • Between two randomly chosen, nonrelated individuals: 1 in 10,000
Types of graft based on histocompatibility between donor and recipient
Type Definition Examples
Autograft
  • Graft originates from the recipient.
Isograft
  • Graft originates from a genetically identical person (identical twin).
Allograft
  • Graft originates from a genetically different person.
Xenograft
  • Graft originates from a different species (e.g., pig).

Immunosuppressive therapy is not required for autograft transplantation.

Deceased and dying donors

Organ donation can save lives, and doctors play an important role in the organ donation system. Doctors should always honor their patients' end-of-life wishes and provide the best possible care, but they should also recognize the medical and social benefits of organ donation. When treating a dying patient, it is therefore important to initiate conversations with the patient and their family about the potential for organ donation. Due to the ethical concerns associated with organ donation, there are several procedures in place to protect the interests of the patient while expanding the practice of donation.

Legal and organizational aspects of organ donation

  • An individual may register to become an organ donor (e.g., in a state donor registry) and can revoke this decision at any time.
  • Donors may specify the solid organs they wish to donate (e.g., heart, two lungs, two kidneys, pancreas, liver).
  • The organ is retrieved from a donor after brain-death (DBD) or a donor after circulatory death (DCD).
  • Deceased patients who have not specifically declined to become donors (e.g., in an advance directive) may be considered if consent is obtained from the next of kin.
  • Dying patients (e.g, terminally ill, in palliative care) who have not previously opted-in to the donation system may also be considered for organ donation.
  • To avoid any conflict of interest, the decision to end life-sustaining care is always made by a medical team that is independent of the transplant team.
  • If the individual is a donor candidate and did not explicitly decline to donate organs (e.g., in a living will) the hospital notifies the local Organ Procurement Organization (OPO).
  • Factors that the OPO will consider:
    • Is there an organ donation plan?
    • If no such plan exists, did the deceased declare their intention to donate organs (e.g., by registering in the state organ donor registry)?
    • If the patient did not declare their intention to donate organs, the OPO discusses the possibility of donation with the patient's next of kin.
    • Is the patient a suitable candidate for donation?

Organ assessment and matching

  • The Organ Procurement and Transplant Network (OPTN) is a national system that links all professionals involved in organ donation and transplantation (e.g., OPOs, transplant centers, histocompatibility laboratories).
  • It is administered by the United Network for Organ Sharing (UNOS), a private nonprofit organization contracted by the federal government.
  • The UNOS manages the national transplant waiting list and works with OPOs to match donors with recipients.
  • Guidelines for matching include donor compatibility, medical utility, geography, and survival benefit of the transplant.
  • The following are the expected waiting periods for new transplant candidates:
  • Contraindications for the acceptance of organs include: [1][2]
  • Circumstances under which organ transplants can be accepted include:

Living donors

  • Overview
    • Nonvital organs and tissues (e.g., kidney or bone marrow) can be acquired from living donors.
    • The organ is retrieved from a living donor (usually a relative with a compatible blood type) at the time of the transplant surgery.
    • When there is no relative with blood type compatibility, a donor may engage in a swap transplantation with a nonrelated donor.
    • Prior to donation, donors must give full informed consent.
    • Donors may select the recipient of their donation.
    • Donors may not be paid for their donation, but can be reimbursed for associated costs (e.g., travel, food, lost wages).
    Advantages
    • Donor is usually healthy, which reduces the risk of complications for both donor and recipient.
    • Preoperative and perioperative immunomodulation is possible in the recipient.
    • Short cold ischemia time
    • Minimal waiting time
  • Disadvantages: increased risk of morbidity and mortality in the donor

Organ preservation

  • Hypothermic solutions
    • Extracellular solutions (e.g., Bretschneider solution): ↑ Na+, ↓ K+
    • Intracellular solutions (e.g., University of Wisconsin solution, St. Thomas cardioplegia solution): ↓ Na+, ↑ K+
  • Ischemic times
    • Warm ischemia time: time from the withdrawal of life support in the donor to the initiation of cold organ preservation
    • Cold ischemia time: time from the initiation of cold organ preservation to the warming of the organ within the recipient following the restoration of blood perfusion

A prolonged ischemic time increases the risk of organ dysfunction in the post-transplant period.

Transplantation sites

Overview of organ transplantation sites
Description Examples
Orthotopic
  • The graft is placed in the normal anatomical position.
  • The diseased or nonfunctional organ being replaced is removed.
Heterotopic
  • The graft is placed in a site other than the normal anatomical position.
  • The nonfunctional organ is usually left in place.
Paratopic

Post-transplant immunosuppressive therapy

Immunosuppressive therapy is a balancing act: Too much immunosuppression, and the risk of infection increases; too little, and the risk of rejection increases.

Overview

Two healthy, fully functioning kidneys are an essential requirement for kidney donation by a living donor.

The left kidney is preferred for living-donor transplantation as it has a longer renal vein.

Complications

Post-transplant care

Diagnostic algorithm for renal dysfunction following renal transplantation

  1. Consider prerenal causes of acute renal failure.
  2. Measure urine protein and order a dipstick urine test for hematuria.

Prognosis

The graft functions stays functional for ∼ 14 years, longer if received from a living donor.

Overview of survival rates after kidney transplantation
1-year survival rate 2-year survival rate 5-year survival rate
Cadaveric graft 88% 81% 71%
Graft from living donor 94% 93% 84%

Renal transplantation has a better prognosis than dialysis in end-stage renal disease.

Overview [7]

Complications

Diagnostic algorithm in the case of clinical or laboratory features of hepatic dysfunction

Post-transplant care

Prognosis

Overview [9][10][11]

Complications

Post-transplant care

Prognosis

Overview of survival rates after heart transplantation
1-year survival rate 3-year survival rate 5-year survival rate
Primary transplants
  • 87%
  • 79%
  • 72%
Retransplants
  • 82%
  • 67%
  • 58%

Overview [12]

Complications

Post-transplant care

Prognosis

  • Median survival for all adult recipients: 5.7 years
  • 1-year survival rate: 78%
  • 5-year survival rate: 51%

Hematopoietic stem cell

Overview of hematopoietic stem cell grafts
Bone marrow transplant Peripheral blood stem cell transplant Umbilical cord blood transplant
Source
Risk of graft-vs-host disease (GvHD)
  • Lowest
  • Highest
  • Low
Engraftment
  • By 3 weeks
  • By 2 weeks
  • By 4 weeks

Types of hematopoietic stem cell transplantation (HSCT)

Autologous vs. allogeneic stem cell transplantation
Autologous stem cell transplantation Allogeneic stem cell transplantation
Definition
Indications [14]
Preferred graft source
Advantages
Disadvantages

Procedure

  1. Preparation of a hematopoietic stem cell graft from the donor using bone marrow aspirate, peripheral blood, or umbilical cord blood
  2. Transplant preparative regimen: recipient preparation using high-dose chemotherapy and/or total body irradiation
  3. Intravenous injection of the harvested hematopoietic stem cells
  4. Stem cell engraftment: anatomical and functional incorporation of transfused hematopoietic stem cells in the recipient's bone marrow
  5. In allogeneic stem cell transplantation: regimen to prevent GvHD

Complications

Hepatic venoocclusive disease (hepatic VOD) [15]

Engraftment syndrome [16]

Other

The mortality rate of allogeneic stem cell transplantation is declining but is still as high as 50%.
When considering a regimen to prevent GvHD following allogeneic HSCT for hematological malignancies, the risk of GvHD should always be weighed against the loss of a beneficial graft-vs-tumor effect and the risk of graft failure due to drug toxicity.

Complications after transplantation can be divided into graft-related (graft rejection, graft-versus-host disease) and immunosuppression-related complications (infection, malignancy).

We list the most important complications. The selection is not exhaustive.

Graft rejection

  • Definition: graft failure as a result of damage to the graft by the host's immune response
Types of graft rejection
Hyperacute rejection Acute rejection Chronic rejection
Frequency
  • < 1% of post-transplant organ dysfunction
  • ∼ 50% of post-transplant organ dysfunction
  • ∼ 50% of post-transplant organ dysfunction
Onset
  • < 48 hours after transplantation (usually within minutes to hours)
  • < 6 months after transplantation (usually within weeks to months)
  • > 6 months after transplantation (usually after a few years)
Risk factors

[18]

Pathophysiology
Clinical features
  • Intraoperative assessment: swelling of the organ as soon as perfusion is restored
  • Slow, progressive loss of organ function
Diagnostics
Treatment Graft removal Graft removal
Prevention
  • Irreversible process with no known prevention

Graft rejection manifests as a failure of the transplanted organ and is very difficult to distinguish from other post-transplant complications. A biopsy is required to confirm the diagnosis.

Graft-versus-host disease (GvHD)

Types of GvHD

Acute GvHD Chronic GvHD
Epidemiology
  • Incidence
    • Without prophylaxis: 70–100%
    • With prophylaxis: 9–50%
Onset
  • < 100 days after transplantation
  • > 100 days after transplantation
Pathophysiology
  • Mostly unknown
Clinical features
Diagnostics
Treatment [22]
Prevention

The skin, intestines, and liver are the most commonly affected organs in GvHD.

Infection

Overview of post-transplant infections
Time of onset Infection

Early onset

(< 1 month after transplantation)

Late onset 1–6 months
6–12 months
> 12 months

Post-transplant malignancy

Pretransplant measures [23]

Posttransplant measures [21]

Because the symptoms of CMV infections can appear similar to those of transplant rejection, differentiating between conditions can be difficult.

  1. Tomblyn M, Chiller T, Einsele H, et al. Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective. Biol Blood Marrow Transplant. 2009; 15 (10): p.1143-1238. doi: 10.1016/j.bbmt.2009.06.019 . | Open in Read by QxMD
  2. Williams WW, Taheri D, Tolkoff-Rubin N, Colvin RB. Clinical role of the renal transplant biopsy. Nat Rev Nephrol. 2012; 8 (2): p.110-121. doi: 10.1038/nrneph.2011.213 . | Open in Read by QxMD
  3. Valenzuela NM, Reed EF. Antibodies in transplantation: the effects of HLA and non-HLA antibody binding and mechanisms of injury. Methods Mol Biol. 2013; 1034 : p.41-70. doi: 10.1007/978-1-62703-493-7_2 . | Open in Read by QxMD
  4. Corrêa RRM, Machado JR, da Silva MV, et al. The Importance of C4d in Biopsies of Kidney Transplant Recipients. Clinical and Developmental Immunology. 2013; 2013 : p.1-8. doi: 10.1155/2013/678180 . | Open in Read by QxMD
  5. Foster PF, Sankary HN, Hart M, Ashmann M, Williams JW. Blood and graft eosinophilia as predictors of rejection in human liver transplantation.. Transplantation. 1989; 47 (1): p.72-4. doi: 10.1097/00007890-198901000-00016 . | Open in Read by QxMD
  6. Martin PJ, Rizzo JD, Wingard JR et al. First- and Second-Line Systemic Treatment of Acute Graft-versus-Host Disease: Recommendations of the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2012; 18 (8): p.1150-1163. doi: 10.1016/j.bbmt.2012.04.005 . | Open in Read by QxMD
  7. The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: A 10-year update.
  8. Mancini D, Lietz K. Selection of Cardiac Transplantation Candidates in 2010. Circulation. 2010; 122 : p.173-183. doi: 10.1161/CIRCULATIONAHA.109.858076 . | Open in Read by QxMD
  9. Canter CE, Shaddy RE, Bernstein D et al. Indications for heart transplantation in pediatric heart disease. Circulation. 2007; 115 (5): p.658-676. doi: 10.1161/CIRCULATIONAHA.106.180449 . | Open in Read by QxMD
  10. Weill D et al.. A consensus document for the selection of lung transplant candidates: 2014—An update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. The Journal of Heart and Lung Transplantation. 2015; 34 (1): p.1-15. doi: 10.1016/j.healun.2014.06.014 . | Open in Read by QxMD
  11. Organ Procurement and Transplantation Network - National Data. https://optn.transplant.hrsa.gov/data/view-data-reports/national-data. Updated: August 21, 2019. Accessed: August 23, 2019.
  12. Kotloff RM, Blosser S, Fulda GJ, et al. Management of the Potential Organ Donor in the ICU. Crit Care Med. 2015; 43 (6): p.1291-1325. doi: 10.1097/ccm.0000000000000958 . | Open in Read by QxMD
  13. New Organ Procurement Organization (OPO) Survey Protocol and Guidance Revisions in Appendix Y of the State Operations Manual (SOM). https://www.cms.gov/Medicare/Provider-Enrollment-and-Certification/SurveyCertificationGenInfo/Downloads/QSO18-23-OPO.pdf. Updated: August 10, 2018. Accessed: October 16, 2020.
  14. Final Human Immunodeficiency Virus (HIV) Organ Policy Equity (HOPE) Act Safeguards and Research Criteria for Transplantation of Organs Infected With HIV. https://optn.transplant.hrsa.gov/learn/professional-education/hope-act/. Updated: November 20, 2015. Accessed: August 26, 2019.
  15. Nashar K, Sureshkumar KK. Update on kidney transplantation in human immunodeficiency virus infected recipients. World J Nephrol. 2016; 5 (4): p.300. doi: 10.5527/wjn.v5.i4.300 . | Open in Read by QxMD
  16. Sugi MD, Albadawi H, Knuttinen G, et al. Transplant artery thrombosis and outcomes. Cardiovascular Diagnosis and Therapy. 2017; 7 (S3): p.S219-S227. doi: 10.21037/cdt.2017.10.13 . | Open in Read by QxMD
  17. Lerman M, Mulloy M, Gooden C, et al. Post transplant renal vein thrombosis, with successful thrombectomy and review of the literature. International Journal of Surgery Case Reports. 2019; 61 : p.291-293. doi: 10.1016/j.ijscr.2019.07.066 . | Open in Read by QxMD
  18. Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. https://www.aasld.org/sites/default/files/guideline_documents/Evaluation_for%20LT_in_Adults_hep26972_0.pdf. Updated: March 1, 2014. Accessed: March 27, 2017.
  19. Hutchinson E. Hepatic artery thrombosis. Nature Reviews Gastroenterology & Hepatology. 2010; 7 (2): p.69-69. doi: 10.1038/nrgastro.2009.223 . | Open in Read by QxMD
  20. Majhail NS, Farnia SH, Carpenter PA et al. Indications for Autologous and Allogeneic Hematopoietic Cell Transplantation: Guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2015; 21 (11): p.1863-1869. doi: 10.1016/j.bbmt.2015.07.032 . | Open in Read by QxMD
  21. Senzolo M. Veno occlusive disease: Update on clinical management. World Journal of Gastroenterology. 2007; 13 (29): p.3918. doi: 10.3748/wjg.v13.i29.3918 . | Open in Read by QxMD
  22. KA AA, E M. Engraftment Syndrome: An Updated Review. Journal of Stem Cell Biology and Transplantation. 2017; 01 (03). doi: 10.21767/2575-7725.100016 . | Open in Read by QxMD
  23. Gutiérrez-García G, Rovira M, Magnano L, et al. Innovative strategies minimize engraftment syndrome in multiple myeloma patients with novel induction therapy following autologous hematopoietic stem cell transplantation. Bone Marrow Transplant. 2018; 53 (12): p.1541-1547. doi: 10.1038/s41409-018-0189-2 . | Open in Read by QxMD
  24. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. McGraw-Hill Education ; 2015
  25. Brunicardi F, Andersen D, Billiar T, et al.. Schwartz's Principles of Surgery. McGraw-Hill Education ; 2014
  26. Williams NS, Bulstrode C, O'Connell PR. Bailey & Love's Short Practice of Surgery. CRC Press ; 2013

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