Transplant medicine

Question 1

Acute renal allograft rejection

Answer 1

Two principal histologic forms of acute rejection:
- Acute T cell-mediated (cellular) rejection (TCMR): lymphocytic infiltration of the tubules, interstitium, and, in some cases, the arterial intima.
- Active (acute) antibody-mediated rejection (ABMR): dx requires 1) Histologic evidence of acute tissue injury, 2) Evidence of antibody interaction with vascular endothelium (eg, C4d staining in peritubular capillaries), 3) Serologic evidence of circulating donor-specific antibodies

Question 2

Risk factors for the development of acute rejection

Answer 2

• Pre-sensitization (ie, presence of donor-specific antibodies or a high panel reactive antibody)
• Human leukocyte antigen (HLA) mismatches
• Pediatric recipient
• Blood group incompatibility
• Prolonged cold ischemia time
• Delayed graft function
• Previous episode of rejection
• Patient receiving a second or greater transplant
• Medication nonadherence

Question 3

Symptoms of acute rejection episodes

Answer 3

• Most patients who have acute rejection episodes are asymptomatic
• Patients can present with fever, malaise, oliguria, and graft pain and/or tenderness but these symptoms are rare with modern immunosuppressive drug regimens

Question 4

Chronic active ABMR

Answer 4

• Chronic active antibody-mediated rejection
• Lacks evidence of acute inflammation and demonstrates findings consistent w/ matrix synthesis
• Generally develops late (>6m post-transplant)
• Occurs in pts w/ or w/o hx of active ABMR
• Difference b/w diagnostic criteria for chronic active and active ABMR: Histologic evidence of chronic (rather than acute tissue injury) in chronic ABMR; otherwise, remaining 2 criteria are same

Question 5

Mixed acute rejection

Answer 5

• Involves acute TCMR and ABMR occurring within the same renal allograft
• May be misdiagnosed as having only TCMR or ABMR, which can lead to these patients being undertreated or incorrectly treated

Question 6

Late pulmonary complications after HSCT

Answer 6

• Most common: cGVHD which manifests as obliterative bronchiolitis (OB), organizing pneumonia, or nonclassifiable interstitial pneumonia
• Other less common: air leak syndrome (ALS), posttransplant lymphoproliferative disorder (PTLD), pulmonary veno-occlusive disease (PVOD), and pleuroparenchymal fibroelastosis (PPF)

Question 7

cGVHD

Answer 7

• cGVHD complications occur more than 100 days after HSCT
• Noninfectious complications more common than infectious complications
• cGVHD is most common complication in long term survivors of HSCT patients

Question 8

Conditioning regimens

Answer 8