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Transplantation

Last updated: February 9, 2021

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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 (allogenous 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 allogenous 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), allogenous transplantation subsequently requires immunosuppressive therapy.

Transplant immunology

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

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.

Organ procurement

Deceased donors

Living donors

  • Overview
  • Advantages
    • Donor is in good general condition
    • Preoperative and perioperative immunomodulation is possible in the recipient.
    • Short cold ischemia time
    • Minimal waiting time
    • High degree of HLA compatibility if the donor is related to the recipient
  • Disadvantages: increased 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

Overview

Phases

  1. Induction therapy using anti-T-lymphocyte antibodies
  2. Maintenance therapy: commonly via a triple-drug regimen

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 [5]

Complications

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

Post-transplant care

Prognosis

Overview [7][8][9]

Complications

Post-transplant care

Prognosis

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

Overview [10]

Complications

Post-transplant care

Prognosis

Hematopoietic stem cell

Overview of hematopoetic stem cell grafts
Bone marrow transplant Peripheral blood stem cell transplant Umbilical cord blood transplant
Source
  • Pheresis of peripheral blood after administering a myeloid growth factor (e.g., G-CSF, GM-CSF) or plerixafor (a CXRC4 antagonist) for 4–5 days
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. allogenous stem cell transplantation
Autologous stem cell transplantation Allogenous stem cell transplantation
Definition
Indications

[12]

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
  5. In allogenous stem cell transplantation: regimen to prevent GvHD

Complications

The mortality rate of allogenous stem cell transplantation is declining but is still as high as 50%.
When considering a regimen to prevent GvHD following allogenous 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

[13]

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

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 presentation
Diagnostics
Prevention
Treatment [17]

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

Infection

Overview of post-transplant infections

Early onset

(< 1 month after transplantation)

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

Post-transplant malignancy

Pretransplant measures [18]

Post-transplant measures [16]

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

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  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
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  12. 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.
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  14. 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
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