Leukaemia, treatment

Alemtuzumab - monoclonal antibody leukaemia treatment Allopurinol - prevention of uric acid production, gout treatment Alteplase - fibrinolytic thrombosis Amantadine - antiviral Parkinson s disease Amfetamine (amphetamine) - CNS stimulant (little therapeutic use)... 

Rituximab - monoclonal antibody rheumatoid arthritis, leukaemia treatment Rofecoxib - COX2 inhibitor (withdrawn)... 

Maciel, R. and Minim, L.A., Adaptive control of an open tubular heterogeneous enzyme reactor for extracorporeal leukaemia treatment, J. Process Control, 6, 317, 1996. 

Fig. 18. Dose-response curve for [Au(dppe)2]Cl in mice bearing ip. P388 leukaemia (treatment on days 1 to 5 with a single daily ip. dose). Each point is the average of median survival time at a particular dose in 21 experiments (from Ref. 83)...

Cytarabine, 4-amino-l-/3-D-arabinofuranosylpyrimidin-2(lif)-one or cytosine arabino-side (1033 R = H, X = NH2), is an established drug for the treatment of acute leukaemias of childhood and adult granulocytic leukaemia. It must be given intravenously and much of the drug becomes the corresponding inactive uracil derivative in vivo by virtue of a deaminase in the liver it interferes with DNA but not RNA synthesis, and it has incidental... 

Cytokines and biological response modifiers represent a broad class of therapeutic agents that modify the hosts response to cancer or cancer therapies. The enormous body information about their clinical uses and their side effects is beyond the scope of this essay that can only give illustrative examples. For an up-to-date information the reader can resort to reference [5]. As many as 33 different interleukins are known and the list continues to grow IL-2 used in the treatment of kidney cancer is one example. Interferon alpha is used for chronic myelogenous leukeia, hairy cell leukaemia and Kaposi s sarcoma. Interferons are also used in the treatment of chronic infections such as viral hepatitis. Tumor necrosis factor (alpha), G/GM/M-CSF, and several other cellular factors are used in treatment of various cancers. Many of these cytokines produce serious side effects that limit their use. 

L-Asparaginase, an enzyme derived from E. coli or Erwinia carotovora, has been employed in cancer chemotherapy where its selectivity depends upon the essential requirement of some tumours for the amino acid L-asparagine. Normal tissues do not require this amino acid and thus the enzyme is administered with the intention of depleting tumour cells of asparagine by converting it to aspartic acid and ammonia. Whilst L-asparaginase showed promise in a variety of experimentally induced tumours, it is only useful in humans for the treatment of acute lymphoblastic leukaemia, although it is sometimes used for myeloid leukaemia. 

Thiopurine drugs in the treatment of childhood leukaemia the influence of inherited thiopurine methyltransferase activity on dmg metabolism and cytotoxicity. Br J Clin Pharmacol 1997 44 455-461. 

Lennard L, Gibson BES, Nicole T, Lilleyman JS. Congenital thiopurine methyltransferase deficiency and 6-mer-captopurine toxicity during treatment for acute lymphoblastic leukaemia. Arch Dis Child 1993 69 577-579. 

Clinical trials have shown the recombinant interferons to be effective in the treatment of various cancer types, with rhIFN-a2a and -a2b both approved for treatment of hairy cell leukaemia. This is a rare B-lymphocyte neoplasm for which few effective treatments were previously available. Administration of the recombinant interferons promotes significant regression of the cancer in up to 90 per cent of patients. 

Further studies have shown additional cancer types, most notably ovarian and bladder cancer, non-Hodgkin s lymphoma and acute myeloid leukaemia, to be at least partially responsive to IL-2 treatment. However, a persistent feature of clinical investigations assessing IL-2 effects on various cancer types is variability of response. Several trials have yielded conflicting results, and no reliable predictor of clinical response is available. 

Harousseau, J. 1997. The role of colony-stimulating factors in the treatment of acute leukaemia. Biodrugs 7(6), 448-460. 

Ronghe, M., Burke, G.A., Lowis, S.R, and Estlin, E.J. 2001. Remission induction therapy for childhood acute lymphoblastic leukaemia clinical and cellular pharmacology of vincristine, corticosteroids, L-asparaginase and anthracyclines. Cancer Treatment Reviews 27(6), 327-337. 

Interleukin 1 (IL-1) is produced mainly by activated monocytes-macropha-ges, and its principal action is to stimulate thymocytes. A pleiotropic cytokine, IL-1 induces the expression of a large diversity of cytokines such as IL-6, leukaemia inhibitory factor (LIF), and other proinflammatory molecules (Di-marello 1994). IL-1 and TNF-a carry out as part of their function increasing the expression of NF-/cB and JNK (c-Jun N-terminal kinase). The importance of IL-1 in OCS is demonstrated because the IL-1-receptor-deficient mouse is resistant to ovariectomy (OVX)-induced bone loss (Lorenzo et al. 1998). The importance in pathological bone loss is also illustrated by the fact that treatment with IL-1 receptor antagonist slows down bone erosion for patients affected with rheumatoid arthritis (Kwan et al. 2004). IL-1 increases osteoclast differentiation rather than mature osteoclast activity, and infusion of IL-1 into mice induces hypercalcemia and bone resorption. Finally, IL-1 and TNF-a... 

The URDP/PNP/Ara-U process is used to manufacture nelarabine, a water-soluble prodrug of 9-p-D-arabinofuranosylguanidine produced as a treatment for acute lymphoblastic leukaemia (Scheme 1.29). The two-enzyme process is run at 200 g... 

Millar JL, Millar BC, Powles RL, et al. Liposomal vincristine for the treatment of human acute lymphoblastic leukaemia in severe combined immunodelicient (SCID) mice. Br J Haematol 1998 102 718. 

Humanized and chimerized MAbs have been developed for the treatment of non-Hodgkin lymphoma, renal cell carcinoma, ovarian carcinoma, breast cancer, melanoma, and neuroblastoma [117,119,120,123,124]. Patients with relapsed or refractory myeloid leukaemias that have been treated with HuM95, did not develop significant HAMA responses [59]. 

Vincamine, vinblastine and vincristine are very important clinic alkaloids. They are produced naturally by plants vincamine by Vinca minor, and vinblascine and vincristine by Madagascar periwinkle Catharanthus roseus). The vindoline synthesis pathway starts with strictosidine and, via dehydrogeissoschizine, preakuammicine, stemmadenine and tabersonine, is converted to vindoline and vincristine (Figure 42). Conversion from vindoline to vinblastine is based on the NADH enzyme activity. Vinblastine and vincristine are very similar alkaloids. The difference is that vincristine has CHO connected to N, whereas vinblastine in the same situation has only CO3. This synthetic structural differences influence their activity. Vinblastine is used to treat Hodgkin s disease (a form of lymphoid cancer), while vincristine is used clinically in the treatment of children s leukaemia. Vincristine is more neurotoxic than vinblastine. 

PTD has been evaluated in the treatment of transfused blood going into blood banks, the objective being to inactivate viruses, such as HIV, without affecting erythrocytes. Use of silicon phthalocyanine or naphthalocyanine derivatives allows irradiation at wavelengths where the erythrocytes do not absorb, and the process is reported to be very effective. The use of Photofrin in inactivating HIV-1 in blood has also been described, whilst BPD (see Figure 4.23) has been used to inactivate feline leukaemia retrovirus in both spiked human blood and infected cat s blood. ... 

Intron A (Sobering Plough) Interferon-a (treatment of leukaemia) 1.4... 

Filgrastim also shows therapeutic promise in the treatment of additional conditions characterized by depressed blood neutrophil counts. Such conditions include severe chronic neutropenia, leukaemia and AIDS. 

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