Transplantation & Graft Rejection
provides the opportunity for definitive treatment of end-stage organ disease. The common solid organs transplanted are the kidney and the liver, and less frequently are the heart, lung, and pancreas.Kidney transplantation
The organs are either:1. cadaveric (previously healthy who experienced brain stem death)
2. living related donation (usually close relatives such as siblings).
Contra-indications to receiving a renal transplant
1.Predicted patient survival of less than 5 years2. Predicted risk of graft loss of > 50% at 1 year
3. Patients unable to comply with immuno-
suppressant therapy
4. Immunosuppression predicted to cause life-threatening complications
5. Body mass index (BMI) is of >30
6. Patients with severe vascular access problems
Indications of renal transplants
Renal transplant is used for end-stage renal failure (ESRF) caused by:1. Diabetes mellitus
2. Glomerulonephritis
3. Renovascular disease/vasculitis
4. Pyelonephritis
5. Hypertension
6. Adult polycystic kidney disease (APKD)
Evidence indicate failing kidney transplant
1. Signs of fluid overload
2. Hypertension
3. Tenderness over the graft
4. A tunneled line for haemodialysis
5. Signs of uraemia
6. Cushingoid features
Graft rejections in renal transplants
Hyperacute rejectionThis is due to presence of pre-existing antibodies against the receipt HLA antigens causing thrombosis and tissue necrosis with bleeding.
Acute vascular rejection
1-This is vasculitis due to antibodies formed after transplantation and complement reactions
2-type IV hypersensitivity due to CD4 and CD8 reactions Immuno- suppression is required for prevention and treatment of these conditions.
Chronic allograft failure
This may be due to immunological mechanism or non-immunological ones such as hypertension, hyperlipidaemia and chronic drug toxicity.
Immunosuppressive drugs (ISD)
drugs used in synergistic combinations to minimize drug side effects in the prevention and treatment of these types of rejections .The main risks of using these agents are infections and malignancy.
The risk of infections is minimized by prophylactic use of medications .
Bone marrow and peripheral blood stem cell transplantation
2-Autologus transplant
Stem cells are harvested from the blood or bone marrow of the same patient.1-Allogeneic transplant
Stem cells are taken from the blood or bone marrow of HLA-identical siblings, or closely HLA-matched The BMT is given to the patient intravenously, after chemotherapy with or without radiotherapy that destroys malignant cells, Enough erythrocytes, granulocytes, and platelets are produced after 3-4 weeks of engraftment. The immune system of the recipient is boosted by infusion of T-cells taken from the donor, so called donor lymphocyte infusion (DLI). Long term immunosuppression by fludarabine and cyclophosphamide is required in so called reduced-intensity BMT.Complications of allogeneic BMT
1. Mucositis2. Infections
3. Cataract
4. Pneumonitis
5. Infertility
6. Acute/chronic GvHD
Indications for allogeneic BMT
1. Acute myeloid leukaemia (AML)2. Chronic myeloid leukaemia (CML) resistant to imitanib (Mab)
3. Acute lymphoblastic leukaemia (ALL)
4. Severe aplastic anaemia
5. Myelofibrosis
The outcome of autologous BMT is better than allogeneic BMT since it does not require immunosuppressant, with no risk of GvHD, quicker engraftment in 2-3 weeks
Indications to autologus BMT
1. AML
2. Myeloma
3. Mantle cell lymphoma
Liver transplantation
It is the replacement of a diseased liver with a healthy liver from another person the transplant could be Whole cadaveric liver or Portion Usually the right lobe of living donor liver transplantFull liver functions are achieved in 4-6 weeks.
Post-transplantation immunosuppression is required
Rejection episodes are experienced such as hyperacute, acute , and chronic .
Indications of liver transplantation
1. Cirrhosis
2. Hepatocellular carcinoma with: - One lesion < 5 cm . 3 lesions < 3 cm . extra-hepatic manifestations . No vascular invasion