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Pathology: - phase 1, pre-engraftment, 1st 30 days - neutropenia, mucositis, acute graft vs host disease - phase 2, post-engraftment, 30-100 days - impaired cell-mediated immunity - acute & chronic graft vs host disease - phase 3, late phase, > 100 days - impaired cell-mediated immunity - impaired humoral immunity - chronic graft vs host disease [1] Laboratory: - Toxoplasma gondii serology IgG (all patients) - histoplasmosis serology - Strongyloides serology (ELISA) & stool ova & parasites - tuberculin skin testing - see ARUP consult [4] Radiology: - chest X-ray as needed (rule out tuberculosis) Complications: 1) organ rejection: a) order of increasing tendency for organ rejection: liver > kidney > pancreas b) older organ tranplanted into younger patients results in highest rate of rejection 2) infection a) risk varies with - type of organ transplantation - immunosuppressive agents used - time after transplantation - recipient & donor characteristics (seropositivity) - post-transplantation complications - graft vs host disease - transplant rejection b) CMV 1] most common opportunistic organism in solid organ transplants 2] occurs most commonly in CMV-negative transplant recipient & CMV-positive organ donor 3] non-specific febrile illness vs pneumonitis, colitis, esophagitis, hepatitis, leukopenia &/or thrombocytopenia c) Epstein-Barr virus - associated with B-cell lymphoproliferative disease (seropositive donor, seronegative recipient) d) during the 1st month after transplantation: 1] most infections result from: a] transmission from the donor organ b] surgical complications c] nosocomial exposures d] similar to other types of surgery - C difficile 2] neutropenia & mucositis are major risk factors for bacterial & Candida infections 3] pathogens - Staphylococcus aureus including MRSA - nosocomial gram-negative infections - C difficile colitis - Candidiasis - aspergillosis 4] infections - surgical site infection - nosocomial peumonia - intravenous catheter-associated infection - urinary tract infection [1] e) 1-6 months after transplantation - cytomegalovirus (CMV) - Epstein-Barr virus (EBV) [1] - varicella zoster - Herpes simplex - Pneumocystis jirovecii - Toxoplasma gondii (CNS infection, cardiac infection) - polyomavirus BK virus in renal transplantation patients may cause nephropathy, organ rejection or urethral strictures - Listeria monocytogenes - Trypanosoma - Strongyloides - Aspergillus (lung transplantation, neutropenia) - Nocardia - hepatitis C virus, hepatitis B virus - reactivation of latent tuberculosis - Cryptococcal meningitis [1] f) > 6 months after transplantation: 1] 75% at risk for same infections as general population 2] those transplant patients requiring increased immunosuppression remain at risk of opportunistic infections 3] pathogens - Epstein-Barr virus (EBV) [1] - varicella zoster - polyomavirus (> 12 months after transplantation) - polyomavirus BK virus - polyomavirus JC virus - cytomegalovirus (CMV) (unless both donor & recipient seronegative) [1] 4] infections - community-acquired pneumonia - urinary tract infection [1] g) multidrug-resistant organisms including Pseudomonas species & MRSA are common 3) cancer, including skin cancer* a) recipients of solid organ transplants are at increased risk of cancer - kidney transplant, liver transplant, heart transplant, lung transplant - lymphoma & lung cancer are most common [2] - EBV seronegative patients who receive transplant from EBV seropositive donor are at increased risk for post-transplant lymphoproliferative disease [1] b) cancers may behave aggressively in transplant patients [1] c) aggressive squamous cell carcinoma of the skin preferentially localized on the face (67%) [15] * non-melanoma skin cancer [1] Management: 1) prescribe new medications with caution a) anti-rejection drug effects are wide b) drug interactions are common [1] 2) immunizations prior to transplantation a) influenza virus vaccine (inactivated) annually b) tetanus-diphtheria-inactivated pertussis vaccine (Tdap) - immunize adults who received Tdap as child, regardless of pre vs post transplantation (immunity wanes) [1] c) hepatitis A vaccine (prior to transplantation) d) hepatitis B vaccine (prior to transplantation) e) pneumonia vaccines: PCV13 followed in 8 weeks with PPSV23 f) recombinant Herpes zoster vaccine (Shingrix) age 50 years (prior to transplantation) g) meningococcal polysaccharide vaccine (as per non-transplantation patients) [1] h) inactivated polio vaccine i) in general, avoid live virus vaccines after organ transplantation - measles-mumps-rubella vaccine (MMR) <live virus vaccine> - contraindicated after solid organ transplantation - 24 months after hematopoietic stem cell transplantation (only 1-2 doses, no GVHD or immunosuppression) - varicella virus vaccine <live virus vaccine> - > 4 weeks prior to organ transplantation - contraindicated after solid organ transplantation - 24 months after hematopoietic stem cell transplantation (2 doses if seronegative, no GVHD or immunosuppression) j) Haemophilus influenzae type-B vaccine (hematopoietic stem cell transplantation) k) HPV vaccine (prior to transplantation as per non-transplantation patients) [1] 3) immunizations for hematopoietic stem cell transplantation generally given 6-12 months after transplantation - live virus vaccines contraindicated or given 24 months after transplantation if seronegative & no GVHD or immunosuppression [1] 4) pharmaceuticals: immunosuppressive agents a) most transplantation centers use 3 drugs a) prednisone b) a calcineurin inhibitor 1] cyclosporine 2] tacrolimus c) an antimetabolite, generally mycophenolate mofetil [1] b) other immunosuppressants 1] mTOR inhibitors a] sirolimus b] everolimus 2] other antimetabolites a] azathioprine b] methotrexate c] cyclophosphamide 3] lymphocyte-depleting antibodies a] antithymocyte globulin b] muromonab-CD3 c] basiliximab d] daclizumab e] rituximab f] alemtuzumab 5) CMV prophylaxis a) indicated for transplant recipients at risk for CMV - seropositive donor or recipient - no need if donor & recipient seronegative [1] b) ganciclovir, valganciclovir or high-dose acyclovir c) can reduce risk of lymphoproliferative disease 6) Bactrim is used for prophylaxis against & treatment of Pneumocystis pneumonia 7) prophylaxis with posaconazole for fungal infection for 1st few months in patients with hematopoietic stem cell transplantation [1] 8) prophylaxis with fluconazole & a fluoroquinolone for neutropenic patients 9) treat Candida in the urine of renal transplantation patients a) suspect kidney infection b) fluconazole is usually effective against Candida sp except Candida glabrata & Candida krusei 10) treat Aspergillus early & aggressively 11) Strongyloides should be identified prior to transplantation a) Strongyloides hyperinfestation syndrome may occur during immunosuppression b) treat Strongyloides with thiabendazole or albendazole prior to transplantation

Related

organ donation organ transplantation rejection

Specific

azficel-T (Laviv) cardiac transplantation; heart transplant hematopoietic stem cell transplantation (HSCT) intestinal transplantation liver transplantation lung transplantation meniscal transplantation ovarian tissue transplantation pancreatic transplantation penis transplantation renal transplantation uterine transplantation xenotransplantation

General

transplantation

References

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  2. Engels EA et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA 2011 Nov 2; 306:1891. PMID: 22045767
  3. Tullius SG, Milford E. Kidney allocation and the aging immune response. N Engl J Med 2011; 364:1369-1370. PMID: 21410395
  4. ARUP Consult: Immunosuppressive Drug Optimization and Monitoring - Organ Transplantation Drugs The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/organ-transplantation
  5. Eid AJ, Razonable RR. New developments in the management of cytomegalovirus infection after solid organ transplantation. Drugs. 2010 May 28;70(8):965-81 PMID: 20481654
  6. Nishi SP, Valentine VG, Duncan S. Emerging bacterial, fungal, and viral respiratory infections in transplantation. Infect Dis Clin North Am. 2010 Sep;24(3):541-55 PMID: 20674791
  7. Lemonovich TL, Watkins RR. Update on cytomegalovirus infections of the gastrointestinal system in solid organ transplant recipients. Curr Infect Dis Rep. 2012 Feb;14(1):33-40. PMID: 22125047
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  10. Fishman JA. Infections in immunocompromised hosts and organ transplant recipients: essentials. Liver Transpl. 2011 Nov;17 Suppl 3:S34-7. Review. PMID: 21748845 Free Article
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  13. Weigt SS, Gregson AL, Deng JC, Lynch JP 3rd, Belperio JA. Respiratory viral infections in hematopoietic stem cell and solid organ transplant recipients. Semin Respir Crit Care Med. 2011 Aug;32(4):471-93. Review. PMID: 21858751 Free PMC Article
  14. Trofe-Clark J, Lemonovich TL; AST Infectious Diseases Community of Practice. Interactions between anti-infective agents and immunosuppressants in solid organ transplantation. Am J Transplant. 2013 Mar;13 Suppl 4:318-26. PMID: 23465024 Free Article
  15. Lanz J, Bouwes Bavinck JN, Westhuis M et al Aggressive Squamous Cell Carcinoma in Organ Transplant Recipients. JAMA Dermatol. Published online December 5, 2018 PMID: 30516812 https://jamanetwork.com/journals/jamadermatology/fullarticle/2717171
  16. Angarone M, Ison MG. Diarrhea in solid organ transplant recipients. Curr Opin Infect Dis. 2015 Aug;28(4):308-16. Review. PMID: 26098506
  17. Petrara MR, Giunco S, Serraino D, Dolcetti R, De Rossi A. Post-transplant lymphoproliferative disorders: from epidemiology to pathogenesis-driven treatment. Cancer Lett. 2015 Dec 1;369(1):37-44. Review. PMID: 26279520 Free Article