Table 2.
A summary of the mechanisms of action of drugs used for conditioning and prophylaxis in HSCT patients, with references to paediatric PK studies.
| Drug type | Type | Mode of action | PK Studies |
|---|---|---|---|
| Conditioning | |||
| Fludarabine | Purine analogue | Interferes with ribonucleotide reductase and DNA polymerase, preventing DNA synthesis. | Plunket et al. [195], Salinger et al. [196]. |
| Cyclophosphamide | Nitrogen mustard alkylating agent | Attaches alkyl group to guanine bases in DNA, thus inducing cell apoptosis. Attacks resting and dividing cells. | Tasso et al. [197], Van Hasselt et al. [198]. |
| Melphalan | Nitrogen mustard alkylating agent | Attaches alkyl group to guanine bases in DNA, thus inducing cell apoptosis. Attacks resting and dividing cells. | Van Hasselt et al. [198]. |
| Busulphan | Alkylating anti-neoplastic agent | Alkylation causes adenine–guanine cross-links, causing cell apoptosis. Attacks resting and dividing cells. | Van Hasselt et al. [198]. |
| Treosulphan | Alkylating anti-neoplastic agent | Alkylation causes adenine–guanine cross-links, causing cell apoptosis. Attacks resting and dividing cells. Less toxicity than with busulphan therapy. | Główka et al. [199]. |
| Alemtuzumab | Monoclonal antibody | Binds to CD54, a protein found on the surface of mature lymphocytes but not on haematopoietic stem cells. | Elter et al. [200]. |
| Anti-thymocyte globulin | Polyclonal antibody | Rabbit derived antibodies against human T-cells, formed by injecting human lymphatic cells into a rabbit and harvesting the antibodies produced. | Call et al. [201], Seidel et al. [202]. |
| Prophylaxis | |||
| Cyclosporin | Immuno-suppressant | Lowers immune response and activity of T-cells. Binds to lymphocyte cyclophilin, and the resulting complex inhibits calcineurin, preventing transcription of IL-2. | Willemze et al. [203]. |
| Methotrexate | Antimetabolite | Inhibits metabolism of folic acid, thereby inhibiting purine base synthesis. Mainly inhibits rapidly proliferating cells. | Van Hasselt et al. [198]. |
| Mycophenolate | Immuno-suppressant | Inhibits inosine monophosphate dehydrogenase, the enzyme controlling the rate of synthesis of guanine monophosphate in purine base synthesis in proliferating B- and T-cells. | Downing et al. [204]. |