• Clinical science

Transplantation

Summary

Transplantation is the process of transferring an organ or a part thereof (known as a graft) from one donor to him/herself (autologous transplantation) or to another recipient (allogenous transplantation if the individuals are not identical twins). In addition to being subject to strict legal requirements, the donor and recipient must be histocompatible in allogenous transplantations in order 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., from an identical twin), allogenous transplantation subsequently requires immunosuppressive therapy.

Transplantation biology

Transplant immunology

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

Allorecognition

Prerequisites for organ matching

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

Types of grafts based on histocompatibility between donor and recipient
Type Definition Examples
Autograft
  • Graft originates from the patient him/herself
Isograft
  • Graft originates from a genetically identical person (identical twin)
Allograft
  • Graft originates from genetically different person
Xenograft
  • Graft originates from different species (e.g., pig)

Immunosuppressive therapy is not required for autograft transplantation!

References:[1]

Solid organ transplantation

Organ procurement

  • Deceased donors
  • Living donors
    • The organ is surgically harvested from a living donor (usually a relative) at the time of the transplant surgery.
    • Only kidney transplantation and liver transplantation can be performed using grafts from living donors.
    • Advantages
      • Donor is in good general condition
      • Minimal waiting time
      • Preoperative and perioperative immunomodulation is possible in the recipient.
      • Short cold ischemia time
      • High degree of HLA compatibility if the donor is related to the recipient
    • Disadvantages: increased morbidity and mortality in the donor

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!

References:[2][3][4]

Renal transplantation

Renal transplantation is superior to dialysis in end-stage renal disease (ESRD)!

References:[5][6]

Liver transplantation

References:[5][7][8]

Cardiac transplantation

References:[5][9][10][11]

Hematopoietic stem cell transplantation

Types of HSCT

Autologous stem cell transplantation Allogenous stem cell transplantation
Definition
Indications
  • To allow the administration of higher doses of antineoplastic therapy than would otherwise be possible for certain non-hematological malignancies (e.g., germ cell tumors, soft tissue sarcoma)
  • Multiple myeloma
  • Lymphoma
Advantages
Disadvantages

Complications

The mortality rate of allogenous stem cell transplantation is declining, but is still as high as 50%!

References:[5][12][13]

Complications

Graft-related

Graft rejection

Type of transplant rejection Hyperacute rejection Acute rejection Chronic rejection
Frequency
Onset
  • < 48 hours after transplantation (usually within minutes to hours)
  • < 6 months after transplantation (usually within days to weeks)
  • > 6 months after transplantation (usually after a few years)
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 presents 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

Acute graft-versus-host disease Chronic graft-versus-host disease
Onset
  • < 100 days after transplantation
  • > 100 days after transplantation
Pathophysiology
  • Mostly unknown
Clinical presentation
Diagnostics
Prevention
Treatment

The skin, intestines, and liver are the most commonly affected organs in graft-versus-host disease!

Immunosuppression-related

Post-transplant infections

Etiology

Early-onset

(< 1 month after transplantation)

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

Prevention of post-transplant infections

The symptoms of CMV infections can appear similar to those of transplant rejection. Differentiating between conditions can be tricky!

Post-transplant malignancy

References:[5][2][1][14][15][16][17][18][19][20][21][22]

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

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  • 7. Martin P, DiMartini A, Feng S, Brown R Jr, Fallon M. 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.
  • 8. Squires RH, Ng V, Ekong U et al. Evaluation of the pediatric patient for liver transplantation: 2014 practice guideline by the Am. Ass. for the Study of Liver Diseases, Am. Soc. of Transplantation and the North Am. Soc. for Pediatric Gastroenterology, Hepatology and Nutrition. Hepatology. 2014; 60(1): pp. 362–398. doi: 10.1002/hep.27191.
  • 9. Mehra MR, Canter CE, Hannan MM, et al. The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: A 10-year update. url: http://www.jhltonline.org/pb/assets/raw/Health%20Advance/journals/healun/ISHLT_GUIDELINE.pdf Accessed February 21, 2017.
  • 10. Mancini D, Lietz K. Selection of Cardiac Transplantation Candidates in 2010. Circulation. 2010; 122: pp. 173–183. doi: 10.1161/CIRCULATIONAHA.109.858076.
  • 11. Canter CE, Shaddy RE, Bernstein D et al. Indications for heart transplantation in pediatric heart disease. Circulation. 2007; 115(5): pp. 658–676. doi: 10.1161/CIRCULATIONAHA.106.180449.
  • 12. 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): pp. 1863–1869. doi: 10.1016/j.bbmt.2015.07.032.
  • 13. Al-Jaroudi D. XY Chromosome in Acute Lymphocytic Leukemia Female with Secondary Amenorrhea. Cancer Science & Research: Open Access. 2015; 2(1). doi: 10.15226/csroa.2015.00113.
  • 14. 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): pp. 1150–1163. doi: 10.1016/j.bbmt.2012.04.005.
  • 15. AD K, SJ K, CP L, CP M, TC P, Webber P. Textbook of Organ Transplantation. Hoboken, NJ: John Wiley & Sons; 2014.
  • 16. Fishman JA. Evaluation for infection before solid organ transplantation. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/evaluation-for-infection-before-solid-organ-transplantation?source=see_link%20and%20https:%2F%2Fwww.cdc.gov%2Fmmwr%2Fpreview%2Fmmwrhtml%2Frr4910a1.htm. Last updated December 14, 2016. Accessed March 27, 2017.
  • 17. Goljan EF. Rapid Review Pathology. Philadelphia, PA: Elsevier Saunders; 2018.
  • 18. Le T, Bhushan V,‎ Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017.
  • 19. Williams WW, Taheri D, Tolkoff-Rubin N, Colvin RB. Clinical role of the renal transplant biopsy. Nat Rev Nephrol. 2012; 8(2): pp. 110–121. doi: 10.1038/nrneph.2011.213.
  • 20. 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): pp. 1143–1238. doi: 10.1016/j.bbmt.2009.06.019.
  • 21. 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: pp. 41–70. doi: 10.1007/978-1-62703-493-7_2.
  • 22. Higgins RM, Daga S, Mitchell DA. Antibody-incompatible kidney transplantation in 2015 and beyond. Nephrol Dial Transplant. 2014; 30(12): pp. 1972–1978. doi: 10.1093/ndt/gfu375.
  • 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.
  • Centers for Disease Control and Prevention; Infectious Disease Society of America; American Society of Blood and Marrow Transplantation. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr4910a1.htm. Updated October 20, 2000. Accessed March 27, 2017.
  • 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): pp. 1–15. doi: 10.1016/j.healun.2014.06.014.
  • Scientific Registry of Transplant Recipients. OPTN/SRTR 2017 Annual Data Report: Lung. https://srtr.transplant.hrsa.gov/annual_reports/2017/Lung.aspx. Accessed August 18, 2019.
  • Dr. Jonah Odim. 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.
last updated 12/10/2019
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