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Organ transplantation is the strategy of choice for end-stage organ disease. Immunosuppressive therapies have allowed patients to extend the life of the organ but require careful monitoring to prevent toxicity and rejection. Therapeutic ranges and toxic thresholds should be carefully considered based on the clinical setting. Important factors include the organ transplanted, time posttransplant, age and clinical status of the patient, and concomitant medications.
Immunosuppressive Drug Regimens for Organ Transplants | |||
Available Immunosuppressives (immunosuppressive regimen depends on organ transplanted; most common combination is steroid plus calcineurin) | Mechanism of Action | Toxicity | Therapeutic Ranges |
Antithymocyte globulin (ATG®, Atgam®, Thymoglobulin®) | Depletes lymphocytes | Increases risk of infection | Aim for 0.1-0.3 lymphocytes/mL |
Corticosteroids | Proapoptotic effect on lymphoid cells; suppresses eicosanoid production; increases TGF expression | Increases risk of infection and malignancy (nonmelanoma skin cancers [NMSC]) | |
IL-2 antibodies
| Selectively blocks IL-2 receptors on T helper cells, preventing T-cell proliferation | Increases risk of malignancy (NMSC and lymphomas) | |
OKT3 (Muromonab CD3®) | Depletes lymphocyte T-cells | Increases risk of infection | 500-1,500 ng/mL during steady state treatment |
| Alemtuzumab (Campath-IH) | Targets CD52 on T-cells, B-cells, and NK-cells, causing depletion | Increases risk of infection | |
| Rituximab (Rituxan®, MabThera®) | Binds CD20 and B-cells mediating lysis | Increases risk of infection | |
| Belatacept (LEA 29Y) | Binds to T-cells to prevent CD28 signalling | Increases risk of infection | |
Immunosuppressants | |||
| Inhibits purine nucleotide synthesis, which interferes with DNA synthesis | Increases risk of infection and malignancy (acute myeloid leukemia and myelodysplastic syndromes) | |
| Selectively inhibits inosine monophosphate dehydrogenase – interferes with DNA purine synthesis | Increases risk of infection | Measured as trough level; therapeutic range not well established |
| Blocks B- and T-cell proliferation by blocking pathway between IL-2 receptor and nucleus; does not block calcineurin pathway; synergistic with cyclosporine | Increases risk of hyperlipidemia and infection | Measured as trough level
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| Inhibits calcineurin phosphatase and reduces IL-2 expression | Increases risk of malignancy, nephrotoxicity, cardiotoxicity, hyperlipidemia | Cyclosporine therapeutic ranges for kidney post-transplant measured 2 hours after first dosing
Cyclosporine therapeutic ranges for liver post-transplant
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| Inhibits calcineurin phosphatase and reduces IL-2 expression | Increases risk of malignancy, nephrotoxicity, cardiotoxicity, hyperlipidemia | Measured as trough level Tacrolimus therapeutic ranges for kidney and liver
Tacrolimus therapeutic ranges for heart
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Tests generally appear in the order most useful for common clinical situations
| Test name: Cyclosporine A by Tandem Mass Spectrometry |
| ARUP #: 0070035 |
| Methodology: Quantitative Liquid Chromatography-Tandem Mass Spectrometry |
| Use: Optimize dosage; monitor compliance |
| Limitations: Concentrations determined by mass spectrometry may be 10-50% lower than those observed by immunoassay methods due to greater specificity of the assay for the parent drug |
| Test name: Everolimus by Tandem Mass Spectrometry |
| ARUP #: 0092118 |
| Methodology: Quantitative Liquid Chromatography-Tandem Mass Spectrometry |
| Use: Optimize dosage; monitor compliance Optimal therapeutic range for a given patient may differ based on treatment phase (initiation or maintenance), use in combination with other drugs, time of specimen collection relative to prior dose, type of transplanted organ or the therapeutic approach of the transplant center |
| Test name: Mercaptopurine Quantitation, Serum or Plasma |
| ARUP #: 0091084 |
| Methodology: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry |
| Use: Monitor compliance |
| Limitations: Measures concentration of parent drug only; risk of toxicity associated with TPMT deficiency should be evaluated by TPMT, RBC |
| Test name: Mycophenolic Acid |
| ARUP #: 0090213 |
| Methodology: High Performance Liquid Chromatography |
| Use: Optimize dosage; monitor compliance |
| Limitations: In vitro conversion of parent drug to mycophenolic acid can occur if specimens are collected shortly after IV administration and could contribute to falsely elevated concentrations of mycophenolic acid Therapeutic ranges and toxic thresholds are not well established |
| Test name: Sirolimus by Tandem Mass Spectrometry |
| ARUP #: 0098467 |
| Methodology: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry |
| Use: Optimize dosage; monitor compliance |
| Limitations: Concentrations determined by mass spectrometry may be 10-50% lower than those observed by immunoassay methods due to greater specificity of the assay for the parent drug |
| Test name: Tacrolimus by Tandem Mass Spectrometry |
| ARUP #: 0090612 |
| Methodology: Quantitative Liquid Chromatography-Tandem Mass Spectrometry |
| Use: Optimize dosage; monitor compliance |
| Limitations: Concentrations determined by mass spectrometry may be 10-20% lower than those observed by immunoassay methods due to greater specificity of the assay for the parent drug |
| Test name: Thiopurine Methyltransferase, RBC |
| ARUP #: 0092066 |
| Methodology: Enzymatic/Quantitative Liquid Chromatography-Tandem Mass Spectrometry |
| Use: Identify patients at risk for severe toxicity with azathioprine or 6-mercaptopurine |
| Limitations: Requires blood sample collected prior to thiopurine drug administration Prefer that the patient has not received a blood transfusion during the two weeks prior to blood collection TPMT enzyme activity can be inhibited by several drugs including the following
Patients should abstain from these drugs for at least 48 hours prior to TPMT testing in order to avoid falsely low results |
| Test name: Lymphocyte Transplantation CD3 |
| ARUP #: 0095949 |
| Methodology: Quantitative Flow Cytometry |
| Use: Monitor immunosuppressive therapy with OKT3; test verifies CD3 antigen removal |
| Follow-up: For testing of immunocompromised patients, order Lymphocyte Subset Panel 4 - T-Cell Subsets Percent and Absolute |
| Test name: Lymphocyte Transplantation Profile |
| ARUP #: 0095798 |
| Methodology: Quantitative Flow Cytometry |
| Use: Monitor immunosuppressive therapy with anti-lymphocyte drugs such as OKT3 or ATG (anti-thymocyte globulin) |