Chapter 21: Organ Transplantation

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1

What are the two essential principles of organ transplantation?

  1. the immunology underlying donor and recipient matching
  2. the need for immunosuppressive therapy
2

What are two unique features of hematopoietic cell transplantation (HCT) compared to solid organ transplantation?

  1. there is no sophisticated surgical procedure but rather a cellular infusion of hematopoietic stem cells
  2. rather than risk of long-term chronic graft rejection, the complication is graft-versus-host disease (GVHD)
3

What are two critical oral complications of organ transplantation?

Organ transplant recipients are at high risk for developing oral infections as well as noninfectious long-term complications, including oral cancer.

4

What is the most common indication for kidney transplantation?

The most common indication is end-stage renal disease secondary to glomerulonephritis, pyelonephritis, or nephropathy.

5

What are the most common indications for heart transplantation? (3)

The primary indications include

  1. severe cardiomyopathy,
  2. severe coronary artery disease, and
  3. congenital heart disease.
6

What are the most common indications for liver transplantation? (9)

The clinical indications including

  1. extrahepatic biliary atresia,
  2. primary biliary cirrhosis,
  3. chronic hepatitis (HCV infection),
  4. advanced cirrhosis,
  5. sclerosing cholangitis,
  6. nonalcoholic steatohepatitis,
  7. alcoholic liver disease,
  8. fulminant hepatic failure, and
  9. hepatobiliary cancers.
7

What is the most common indication for pancreatic transplantation?

The primary indication is in persons with type I diabetes mellitus who have or are at high risk of secondary complications.

8

What is an effective alternative to whole-pancreas transplantation?

Pancreatic islet cell transplantation, in which islet cells are isolated from the donor pancreas and infused into the recipient.

9

What are the most common indications for liver transplantation? (5)

Indications for lung transplantation include

  1. chronic obstructive pulmonary disease,
  2. α1-antitrypsin deficiency,
  3. idiopathic pulmonary fibrosis,
  4. cystic fibrosis, and
  5. idiopathic pulmonary arterial hypertension (IPAH).
10

What is the most common indication for intestinal transplantation?

Intestinal transplantation is a lifesaving procedure indicated for management of intestinal failure (IF) secondary to a range of pathologic conditions.

11

What are the most common indications for hematopoietic cell transplantation (HCT)? (6)

The most common indications for HCT include

  1. acute and chronic leukemia,
  2. myelodysplastic syndrome,
  3. lymphoma,
  4. aplastic anemia,
  5. severe immunodeficiency syndromes, and
  6. hemoglobinopathies.
12

What is a composite tissue allotransplantation?

Composite tissues that may be transplanted include skin, mucosa, muscle, and bone, used to replace lost or dysfunctional anatomic structures.

13

What two tests are used to match organ donors and recipients?

Donors and recipients are matched using two different laboratory tests:

  1. First, HLA antigen expression is determined on donor and recipient leukocytes through serologic or more frequently DNA-typing assays.
  2. Second, serologic cross-matching functionally measures recipient immune cell response to exposure to donor cell antigens.
14

What is necessary to prevent acute and chronic graft rejection?

Despite optimal HLA matching, nonspecific immunosuppressive agents are necessary to prevent acute and chronic graft rejection.

15

What are the main classes of immunosuppressive medications used in transplant medicine? (4)

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  1. corticosteroids (prednisone)
  2. antimetabolites (azathioprine)
  3. calcineurin inhibitors (cyclosporine, tacrolimus)
  4. mTOR inhibitors (sirolimus, everolimus)
16

What type of graft rejection occurs within 48 hours of transplantation?

Hyperacute rejection occurs within 48 hours of transplantation, is mediated by antibodies and complement activation, and requires graft removal.

17

What type of graft rejection occurs within 90 days of transplantation?

Acute rejection occurs within 90 days of transplantation, is mediated by T cells and antibodies, and responds to steroids and antilymphocyte therapies.

18

What type of graft rejection occurs over 90 days after transplantation?

Chronic rejection of solid organs is primarily antibody mediated and, despite treatment with immunosuppressive medications, is generally irreversible.

19

What is the primary adverse effect of any immunosuppressive therapy?

Immunosuppressive medications nonspecifically block T- and B-cell activity, significantly increasing the risk for infection.

20

Which transplant recipients are at highest risk for infection?

HCT recipients are at highest risk for infection because the entire immune system in effect is reconstituted over a period of months to years.

21

What is an adverse effect specific to cyclosporine and tacrolimus?

CNI therapy is associated with development of chronic kidney disease and renal insufficiency that can progress to end-stage renal disease.

22

What are adverse effects are specific to mycophenolate? (2)

Mycophenolate is associated with myelosuppression and gastrointestinal (GI) side effects (diarrhea and inflammatory bowel disease–like condition).

(Azathioprine has a similar mechanism of action as mycophenolate but is used less frequently because of less favorable side effect profile.)

23

What are adverse effects specific to prednisone? (5)

Side effects of prednisone therapy increase with dose and duration and include

  1. insulin resistance,
  2. hypertension,
  3. hyperlipidemia,
  4. osteoporosis and
  5. avascular necrosis.
24

What are adverse effects specific to sirolimus and everolimus? (2)

The mTOR inhibitors are associated with cytopenia and hyperlipidemia, requiring routine laboratory and blood level monitoring.

25

What two types of cancers are most common in organ transplant recipients?

Organ transplant patients are at increased risk for posttransplant lymphoproliferative disease (PTLD) and nonmelanoma skin cancers.

26

What complication is most specific to renal transplant recipients?

Although BK virus infection can affect any transplant patient, renal transplant recipients are at particular risk for BK virus nephropathy.

27

What complication is most specific to heart transplant recipients?

Cardiovascular disease affecting the transplanted heart can arise from the donor heart because of preexisting pathology.

(All heart transplant recipients receive lifelong statin therapy.)

28

What complication is most specific to liver transplant recipients?

Both HCV infection and alcohol abuse have high likelihoods of recurrence and require routine screening and active treatment if detected.

29

What complication is most specific to lung transplant recipients?

Bronchiolitis obliterans, the characteristic feature of chronic rejection, is therefore diagnosed and monitored based primarily on spirometry.

30

What complication is most specific to HCT recipients?

Potentially life-threatening GVHD, in which engrafted donor lymphocytes mount an alloimmune-mediated attack against the recipient–host tissue.

31

What type of GVHD occurs more than 100 days after HCT?

Chronic GVHD typically occurs after day 100, affecting the skin, mouth, eyes, liver, and lungs, contributing to significant disability and mortality.

32

What laboratory tests should be routinely performed in nearly all organ transplant recipients?

A lipid panel and diabetes screening test should be ordered every 6 to 12 months, especially in patients on long-term CNI and corticosteroid therapies.

33

What laboratory tests should be routinely performed in renal transplant recipients specifically?

Monitoring of serum creatinine is important in renal transplant recipients to screen for rejection, as well as in all patients on CNIs of potential renal toxicity.

34

What laboratory tests should be routinely performed in liver transplant recipients specifically?

Liver function testing is routinely performed in liver transplant recipients because rejection causes elevated ALT, AST, bilirubin, and ALP.

35

What laboratory tests should be routinely performed in lung transplant recipients specifically?

Pulmonary function is monitored by spirometry and indicated in lung transplant patients as well as HCT patients with GVHD.

36

What test is routinely used to screen for solid organ rejection?

Surveillance needle biopsy is routinely performed for most solid organs to screen for rejection.

37

What constitutes triple-drug immunosuppressive therapy?

In solid organ transplantation, this typically consists of triple-drug therapy with

  1. a corticosteroid (prednisone, tapered over a period of weeks)
  2. a calcineurin inhibitor (cyclosporine or tacrolimus)
  3. a purine synthesis inhibitor (almost exclusively mycophenolate)
38

What is the standard GVHD prophylaxis regimen following HCT?

GVHD prophylaxis regimens typically consist of a short course of methotrexate combined with a CNI is tapered over a 3- to 6-month period.

39

What drugs are considered "first-line therapy" for rejection and GVHD?

First-line therapy for rejection and GVHD is corticosteroids.

40

What is the objective of pretransplant dental screening and clearance?

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To reduce the risk of infection in the immediate posttransplant period of immunosuppression.

41

How long before transplantation should all necessary dental treatment be completed?

All necessary dental treatment, and in particular extractions or other invasive procedures, should be completed at least 2 weeks before transplantation.

42

What are the three phases of dental management of patients after transplantation?

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The dental management of patients after transplantation can be divided into three phases:

  1. the immediate posttransplant period;
  2. the stable graft period; and
  3. the chronic rejection period
43

What are the oral complications of organ transplantation? (10)

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  1. oral candidiasis
  2. recrudescent HSV infection
  3. gingival overgrowth (cyclosporine associated)
  4. aphthous stomatitis (mTOR inhibitor–associated)
  5. pyogenic granuloma (tacrolimus associated)
  6. orofacial granulomatosis
  7. oral hairy leukoplakia
  8. cancer
  9. oral mucositis
  10. graft-versus-host disease
44
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This patient has acute myelogenous leukemia and is undergoing myeloablative allogeneic hematopoietic cell transplantation. What is the diagnosis?

Oral mucositis is a complication that is unique to HCT characterized by diffuse, nonspecific erythema and ulcerations of the nonkeratinized oral mucosa.

45

What is the management for oral mucositis? (3)

Management includes

  1. diet modifications (e.g. soft, bland foods)
  2. palliative rinses (e.g. viscous lidocaine), and
  3. systemic analgesics (opioids in some cases)
46
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This patient underwent a renal transplant and is currently receiving cyclosporine. What is the diagnosis?

Cyclosporine-associated gingival overgrowth is characterized by fibro-inflammatory enlargement of the gingiva often involving interdental regions.

47

What is the management for cyclosporine-associated gingival overgrowth? (3)

Poor oral hygiene with dental plaque and calculus accumulations increases the risk of this complication significantly. Management includes:

  1. intensive periodontal care,
  2. improved oral hygiene, and
  3. surgical excision by gingivectomy
48
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This patient is receiving tacrolimus following a hematopoietic cell transplant. What is the diagnosis?

Tacrolimus has been associated with nongingival soft tissue fibroinflammatory polyps that closely resemble pyogenic granulomas.

49

What is the management for pyogenic granuloma?

Management is simple surgical excision, although some lesions may respond to intralesional steroid therapy.

50
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This patient is receiving sirolimus following an organ transplant. What is the diagnosis?

mTOR inhibitor therapy is associated with development of painful aphthous-like oral ulcers, referred to as mTOR inhibitor–associated stomatitis.

51

What is the management for mTOR inhibitor–associated stomatitis?

Management with topical and intralesional steroid therapy is generally effective, although in some cases, mTOR inhibitor dose reduction may be considered.

52
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This is a child patient who is receiving tacrolimus after allogeneic hematopoietic cell transplantation. What is the diagnosis?

Atypical orofacial granulomatosis-like oral lesions have been described in pediatric solid organ transplant recipients who received tacrolimus.

53
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A transplant patient presents with corrugated white plaques on the ventrolateral tongue that cannot be removed. What is the diagnosis?

Oral hairy leukoplakia (OHL) is a painless, benign condition associated with Epstein-Barr virus (EBV) replication encountered in patients with immunodeficiency.

54

What is the management for OHL?

OHL is asymptomatic and does not require treatment.

55

What are the most common oral infections in transplant recipients?

The most frequently encountered oral infections in transplant recipients are candidiasis and recrudescent HSV.

56
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This transplant patient presents with generalized white curdlike papules and plaques throughout the oral cavity. What is the diagnosis?

Pseudomembranous candidiasis presents with generalized white curdlike papules and plaques throughout the oral cavity.

57
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This transplant patient presents with patchy redness throughout the oral cavity. What is the diagnosis?

Erythematous candidiasis presents with generalized or more patchy redness.

58

What is the management for oral candidiasis?

Although topical antifungal therapy is available, systemic azole therapy with fluconazole is generally most effective.

59
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This transplant patient presents with irregularly shaped shallow ulcerations on both the lips and tongue. What is the diagnosis?

HSV recrudescence presents as painful lesions that can affect both keratinized and nonkeratinized surfaces.

60

What is the management for recrudescent herpes simplex virus infection?

Management requires systemic antiviral therapy with acyclovir or valacyclovir or rarely foscarnet in cases of acyclovir resistance.

61

What is the major complication associated with allogeneic HCT?

Graft-versus-host disease is a major complication of allogeneic HCT and the leading cause of nonrelapse mortality.

62
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This patient presents with diffuse ulcerations of the lips and tongue following hematopoietic cell transplantation. What is the diagnosis?

Although infrequently involved, oral features of acute GVHD are similar to those of erythema multiforme and are managed with steroids.

63
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This patient presents with oral mucosal lichenoid inflammation following hematopoietic cell transplantation. What is the diagnosis?

The oral cavity is frequently affected by chronic GVHD causing oral mucosal lichenoid inflammation, xerostomia and high risk for dental decay.

64
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This patient presents with superficial saliva-filled blisters primarily on the palate. What is the diagnosis?

Superficial mucoceles are a common feature of GVHD caused by inflammation of minor salivary glands and do not generally require any specific therapy.

65

What is a secondary complication associated with allogeneic HCT?

Organ transplant patients are at increased risk for developing cancer.

66
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This patient presents with palatal ulceration after hematopoietic cell transplantation. What is the diagnosis?

Extramedullary disease can present in the oral cavity as a nonspecific mass or ulceration following hematopoietic cell transplantation.

67
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This patient presents with palatal ulceration after hematopoietic cell transplantation. What is the diagnosis?

Posttransplant lymphoproliferative disease in the oral cavity as a mass or ulceration after hematopoietic cell transplantation.

68
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This patient presents with buccal ulceration after hematopoietic cell transplantation. What is the diagnosis?

Risk of squamous cell carcinoma (SCC) is increased in posttransplant patients, with patients with GVHD after HCT being at particularly high risk.