Anti-Lymphocyte Globulin (ALG)
Anti-Lymphocyte Globulin (ALG) is an anti-human T cell antibody immunosuppressive used in the prevention and treatment of acute rejection in kidney transplantation. It has also been used to induce remission in Aplastic Anaemia. ALG use is less common than ATG use.
Anti-Thymocyte Globulin (ATG)
Anti-Thymocyte Globulin (ATG) is an anti-human T cell antibody immunosuppressive used for transplant induction in highly sensitised patients and in the prevention and treatment of acute rejection in kidney and cardiac transplantation and in the prevention and treatment of GvHD in stem cell transplantation. It is also used to induce remission in Aplastic Anaemia.
ATG depletes T cells by direct complement action and by cell mediate cytotoxicity. Side effects include activation of the T cells and release of IL-2 before the T cells are destroyed thus potentially causing a cytokine storm. For this reason, anti-IL-2 receptor antibodies such as Basiliximab and Daclizumab are increasingly being used in place of ATG.
Azathioprine
Azathioprine is an immunosuppressive antimetabolite. It inhibits purine synthesis. Azathioprine is used in rheumatoid arthritis, granulomatosis with polyangiitis, severe crohn’s disease, severe ulcerative colitis and in kidney transplants to prevent rejection.
Basiliximab
Basiliximab is a chimeric mouse-human monoclonal immunosuppressive antibody to the α chain (CD25) of the IL-2 receptor of T cells. Basiliximab binds to CD25 thus blocking IL-2 from binding to activated lymphocytes.
Basiliximab is used for induction in solid organ transplantation as an alternative to the more potent ATG. Basiliximab is also used in the prevention and treatment of acute rejection in kidney transplantation in combination with ciclosporin and corticosteroid-containing immunosuppression regimens.
Bortezomib
Bortezomib is proteasome inhibitor used for the treatment of relapsed multiple myeloma and mantle cell lymphoma. Proteasomes are thought to support the immortal phenotype of multiple myeloma by rapidly degrading pro-apoptotic factors. Bortezomib binds to the catalytic site of proteasome with high affinity and specificity, inhibiting its action and permitting the activation of programmed cell death.
Bortezomib is one of the options for post-transplant treatment of patients with DSA, often secondary to plasma exchange, IVIg and Rituximab.
Busulfan
Busulfan is a cell cycle nonspecific alkylating antineoplastic agent which causes profound myelosuppression in patients. Alkylating agents are compounds which are capable of adding an alkyl group (CH4) to the guanine nucleotide bases of DNA molecules, causing damage by cross linking the guanine bases. As cancer cells have less error correction of their DNA during replication, they are disproportionately affected when compared to normal cells.
Busulfan is often used together with Cyclophosphamide (Bu/Cy) as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation.
Campath
Campath (also known as Alemtuzumab) is an anti-CD52 recombinant humanized monoclonal antibody used for the treatment of chronic CLL and T cell Lymphoma. It binds to CD52, which is present on all mature lymphocytes but not on stem cells. Binding targets these cells for destruction.
Campath is indicated for the treatment of B-cell chronic lymphocytic leukaemia (B-CLL) in patients who are refractory to first line treatment with Fludarabine. It is also used as an anti-rejection agent in some conditioning regimens for bone marrow transplantation, kidney transplantation and islet cell transplantation.
Carmustine
Carmustine (also known as BCNU) is a mustard gas related compound with an alkylating mechanism of action. Alkylating agents are compounds which are capable of adding an alkyl group (CH4) to the guanine nucleotide bases of DNA molecules, causing damage by cross linking the guanine bases. As cancer cells have less error correction of their DNA during replication, they are disproportionately affected when compared to normal cells.
Carmustine is used in the treatment of several types of brain cancer, for treatment of Multiple Myeloma and for treatment of Hodgkins and non-Hodgkins Lymphoma. It is often used as a conditioning regime prior to allogeneic hematopoietic progenitor cell transplantation for lymphoma as part of the BEAM cocktail which includes BCNU (Carmustine), Etoposide, Arabinoside-C (also known as Cytarabine) and Melphalan.
Cyclophosphamide
Cyclophosphamide, an alkylating agent, is one of the most efficacious immunosuppressive drugs available. Alkylating agents are compounds which are capable of adding an alkyl group (CH4) to the guanine nucleotide bases of DNA molecules, causing damage by cross linking the guanine bases. As cancer cells have less error correction of their DNA during replication, they are disproportionately affected when compared to normal cells.
Cyclophosphamide is used for treatment of autoimmune disorders such as SLE and multiple sclerosis and as a broad-spectrum anti-cancer drug often given together with other drugs for treatment of non-Hodgkin’s lymphoma, leukaemia’s, multiple myeloma, breast and ovarian cancer. Cyclophosphamide is often used together with Busulfan (Bu/Cy) as a conditioning regimen prior to HSCT.
Cyclosporin
Cyclosporin-A is a Calcineurin inhibitor. Calcineurin is a protein phosphatase also known as protein phosphatase 3. In T-cells, activation of the T-cell receptor normally increases intracellular calcium, which acts via calmodulin to activate Calcineurin. Calcineurin then activates NFAT (Nuclear Factor of Activated T-cells) by dephosphorylating it. Upon activation, NFAT is translocated into the nucleus where it upregulates the expression of IL-2 which, in turn, stimulates the growth and differentiation of T cell response. Cyclosporin binds to the cytosolic protein Ciclophilin and the resulting complex binds to and inhibits Calcineurin.
Cyclosporin was used in solid organ transplantation though its use has mostly been overtaken by the use of Tacrolimus.
Cyclosporine and methotrexate has historically been used as GvHD prophylaxis in HSCT.
Cytarabine
Cytarabine (also known as Arabinoside-C/Ara-C) is an anti-metabolite that competes with dCTP for incorporation into DNA, thereby inhibiting DNA synthesis and is used most often to treat acute leukaemia’s and non-Hodgkins lymphomas.
When used as a conditioning regime prior to allogeneic hematopoietic progenitor cell transplantation for lymphoma, it is often part of the BEAM cocktail which includes BCNU (Carmustine), Etoposide, Arabinoside-C (also known as Cytarabine) and Melphalan.
Daclizumab
Daclizumab is, like Basiliximab, a monoclonal immunosuppressive antibody to the α chain (CD25) of the IL-2 receptor of T cells. Daclizumab binds to CD25 thus blocking IL-2 from binding to activated lymphocytes. Daclizumab is used in the prevention and treatment of acute rejection in kidney transplantation. Daclizumab is often used in combination with Glucocorticoids and Cyclosporine.
Dactinomycin
Dactinomycin is a chemotherapy medication that inhibits transcription by binding DNA at the transcription initiation complex and preventing elongation of RNA chain by RNA polymerase.
It is used to treat a number of types of cancer, including Wilms tumour, Childhood rhabdomyosarcoma and other soft-tissue sarcomas, Ewing’s sarcoma, trophoblastic neoplasm, testicular cancer and certain types of ovarian cancer.
Dexamethasone
Dexamethasone is a Glucocorticoids, a steroid hormone that bind to and activate the glucocorticoid receptor, which is expressed on almost every cell and regulates inflammatory and allergic responses. Activation of the glucocorticoid receptor up-regulates the expression of anti-inflammatory proteins and down-regulate the expression of pro-inflammatory proteins.
Dexamethasone is used to treat many inflammatory conditions such as allergic disorders and skin conditions, to treat ulcerative colitis, arthritis, lupus, psoriasis, and breathing disorders. Dexamethasone is also used in induction for HSCT for patient with multiple myeloma and some other haematological malignancies.
Eculizumab
Eculizumab (aka Soliris) is a monoclonal antibody directed against the complement component C5 which is a component on the final common Complement pathway leading to the formation of Membrane Attack Complex (MAC). Eculizumab blocks the cleavage of C5 and thus halts the process of Complement mediated cell destruction.
Eculizumab is licensed in the UK for treating adults and children with atypical haemolytic uraemic syndrome (aHUS) or paroxysmal nocturnal haemoglobinuria (PNH). Transplant centres often wish to use Eculizumab for preventing recurrence of glomerulopathy post‑transplant, however it is a very expensive drug and is not licenced by NICHE for this use.
Etoposide
Etoposide is an alkaloid anticancer that exerts its effect by disrupting the cell cycle. It is used in the treatment of solid tumours, including testicular, breast and small cell lung cancers and some lymphomas. Etoposide acts by inhibiting the enzyme topoisomerase II, which normally unwinds DNA, causing the DNA double strand to break. Cancer cells are less able to repair this damage compared to normal cells and are therefore disproportionately affected.
When used as a conditioning regime prior to allogeneic hematopoietic progenitor cell transplantation for lymphoma, Etoposide is often part of the BEAM cocktail which includes BCNU (Carmustine), Etoposide, Arabinoside-C (also known as Cytarabine) and Melphalan.
Everolimus
Everolimus is a derivative of Sirolimus (aka Rapamycin) and is an mTOR (mammalian Target of Rapamycin) inhibitor. mTOR is a serine-threonine protein kinase that regulates cell growth, proliferation, motility, survival, protein synthesis and transcription. mTOR also functions as a tyrosine protein kinase that promotes the activation of insulin receptors and insulin-like growth factor 1 receptors.
Unlike the Calcineurin inhibitors which block the synthesis of IL-2, the mTOR inhibitors block cell responses to IL-2. Inhibition of mTOR blocks cell responses to IL-2, thereby preventing the differentiation of T cells into effector T cells and into memory T cells.
Everolimus is used as an immunosuppressant to prevent rejection in heart and kidney transplants and for treatment of advanced kidney cancer.
Fludarabine
Fludarabine is a purine analog that inhibits DNA synthesis by interfering with ribonucleotide reductase and DNA polymerase. Fludarabine is highly effective in the treatment of chronic lymphocytic leukaemia (CLL), producing higher response rates than alkylating agents.
Fludarabine is often used in Reduced Intensity Regimes (RIC) prior to stem cell transplantation either alongside reduced intensity TBI or together with Busulfan with or without ATG.
Ifosfamide
Ifosfamide is an alkylating agent often used in the treatment of solid tumours, including testicular, breast and lung cancers and some lymphomas. Alkylating agents are compounds which are capable of adding an alkyl group (CH4) to the guanine nucleotide bases of DNA molecules, causing damage by cross linking the guanine bases. As cancer cells have less error correction of their DNA during replication, they are disproportionately affected when compared to normal cells.
When used for lymphoma treatment, Ifosfamide is often administered together with Cisplatin and Etoposide as part of the ICE cocktail or with Rituximab and ICE as part of the R-ICE cocktail.
Imatinib
Imatinib is a Tyrosine Kinase Inhibitor used to treat CML. It selectively inhibits BRC-ABL, a constitutively active tyrosine kinase typical of CML. Tyrosine Kinase Inhibitors (TKIs) act by inhibiting tyrosine phosphorylation, which is a key step in the signalling pathways which lead to various cellular processes including growth and differentiation. Inhibition disrupts the cell signalling pathway and reduces proliferation.
Use of Imatinib has significantly reduced the need for stem cell transplantation in CML patients.
Infliximab
Infliximab is an anti TNFα monoclonal antibody used in the treatment of many autoimmune diseases including Psoriasis, Crohn’s disease, Ankylosing Spondylitis, Psoriatic Arthritis, Rheumatoid Arthritis and Ulcerative Colitis.
Lenalidomide
Lenalidomide is a derivative of thalidomide. It is an immunomodulatory agent, the exact mechanism of action of which is not known. It has anti-neoplastic, anti-angiogenic and pro-erythropoietic properties.
In the UK, Lenalidomide is licenced in combination with dexamethasone as a second line treatment for multiple myeloma when first line treatment has failed.
Lomustine
Lomustine (also known as CCNU) is a lipid soluble alkylating agent capable of crossing the blood brain barrier and is used most often to treat brain tumours. Alkylating agents are compounds which are capable of adding an alkyl group (CH4) to the guanine nucleotide bases of DNA molecules, causing damage by cross linking the guanine bases. As cancer cells have less error correction of their DNA during replication, they are disproportionately affected when compared to normal cells.
Lomustine is also used to treat Hodgkins and non-Hodgkins Lymphomas.
Melphalan
Melphalan is a nitrogen mustard alkylating agent. Alkylating agents are compounds which are capable of adding an alkyl group (CH4) to the guanine nucleotide bases of DNA molecules, causing damage by cross linking the guanine bases. As cancer cells have less error correction of their DNA during replication, they are disproportionately affected when compared to normal cells.
Melphalan is mainly used in the treatment of multiple myeloma and for ovarian cancer. It is also used as a conditioning regime prior to HSCT for lymphoma as part of the BEAM cocktail which includes BCNU (Carmustine), Etoposide, Arabinoside-C (also known as Cytarabine) and Melphalan.
Methotrexate
Methotrexate (MXT) is a folic acid antagonist that inhibits dihydrofolate reductase, a key enzyme in the synthesis of the amino acids serine and methionine, thereby interfering with the formation of DNA.
Methotrexate is used in the treatment of some autoimmune diseases, including Psoriasis and Rheumatoid Arthritis as well as treatment of many types of cancer including ALL.
Methylprednisolone
Methylprednisolone is a Glucocorticoids, a steroid hormone that bind to and activate the glucocorticoid receptor, which is expressed on almost every cell and regulates inflammatory and allergic responses. Activation of the glucocorticoid receptor up-regulates the expression of anti-inflammatory proteins and down-regulate the expression of pro-inflammatory proteins.
Methylprednisolone is used to treat many different inflammatory conditions such as arthritis, lupus, psoriasis, ulcerative colitis, allergic disorders, gland (endocrine) disorders, and conditions that affect the skin, eyes, lungs, stomach, nervous system or blood cells.
Mycophenolic acid / Mycophenolate mofetil (MMF)
Mycophenolic acid is the active derivative of Mycophenolate mofetil or MMF. It is an antiproliferative immunosuppressant which inhibits purine synthesis thus suppressing T and B cell responses. MMF inhibits primary antibody responses more efficiently than secondary responses.
MMF is indicated for the prophylaxis of acute rejection in kidney and cardiac transplant patients. It is increasingly utilized as a steroid sparing treatment. MMF can be used concomitantly with cyclosporine and corticosteroids.
Prednisolone
Prednisolone is a corticosteroid it is used to treat many different inflammatory conditions such as arthritis, lupus, psoriasis, ulcerative colitis, allergic disorders, gland (endocrine) disorders, and conditions that affect the skin, eyes, lungs, stomach, nervous system or blood cells.
Rituximab
Rituximab is an anti-CD20 recombinant chimeric murine-human monoclonal antibody. It is often used to treat non-Hodgkins lymphoma and CLL. It binds to CD-20 which is expressed on all B cells (but not on plasma cells). Binding triggers a series of cytotoxic immune response resulting in the elimination of B cells. The mechanism of action includes complement-mediated lysis, antibody-dependent cellular cytotoxicity and induction of apoptosis in the malignant lymphoma cells.
Rituximab is used as part of the induction for ABOi kidney transplantation. It is also often one of the options for post-transplant treatment of patients with DSA. Under expert guidance, Rituximab is also indicated for post-transplantation lymphoproliferative disease, Non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, Severe cases of resistant immune modulated disease including idiopathic thrombocytopenia purpura, haemolytic anaemia and systemic lupus erythematosus.
Sirolimus (aka Rapamycin)
Sirolimus is an mTOR (mammalian Target of Rapamycin) inhibitor used in the prevention of rejection in heart and kidney transplants. Unlike the Calcineurin inhibitors which block the synthesis of IL-2, the mTOR inhibitors block cell responses to IL-2. For this reason, Calcineurin nephrotoxicity is often reduced by use of Sirolimus, allowing a reduction in the dose of Cyclosporin/Tacrolimus.
Tacrolimus
Tacrolimus is a Calcineurin inhibitor which is similar in action to cyclosporin. Tacrolimus prevents NFAT dephosphorylation by complexing with the immunophilin FK binding protein 12 (FKB12) creating a new complex which interacts with and inhibits Calcineurin, thereby inhibiting the expression of IL-2 which, in turn, inhibits the growth and differentiation of T cell response.
Tacrolimus is indicated for prophylaxis of graft rejection following liver transplantation, kidney and heart transplantation.