Lymphoid leukaemia

Various pyridazine-A-oxides (including cinnoline A-oxides) have been prepared as potential antitumour agents in Japan [276-278]. Among several 4-nitro-pyridazine 1-oxides tested for activity against rat ascites hepatoma AH-13, 3,6-dimethoxy-4-nitropyridazine 1-oxide (74) has been found to be the most potent compound a minimal effective dose of 5 mg/kg has been estimated [276], Also pyridazine A-oxides of type (75) bearing a bis(2-chloroethyl)ami-nomethyl side-chain at C-6 have been reported to be effective (0.5-5 mg/kg, i.p.) against AH-13 in rats [278]. Both types of compound (74), (75, R = H, Br), however, have been shown to be inactive against mouse lymphoid leukaemia L-1210. 

Kl. Kamihira, S., Yamada, Y., Hirakata, Y, Tsuruda, K., Sugahara, K., Tomonaga, M., Maeda, T, Tsukasaki, K., Atogami, S., and Kobayashi, N., Quantitative characterization and potential function of membrane Fas/APO-1 (CD95) receptors on leukaemic cells from chronic B and T lymphoid leukaemias. Br. J. Haematol. 99, 858—865 (1997). 

Aksoy M. 1987. Chronic lymphoid leukaemia and hairy cell leukaemia due to chronic exposure to benzene report of three cases. BrJ Haematol 66 209-211. 

A cytotoxic alkaloid from Boehmeria cylindrica (Urticaceae), active in cell cultures against Eagle s K.B. carcinoma of the nasopharynx, but inactive against sarcoma 180, adenocarcinoma 755, L-1210 leukaemia, and Walker carcinosarcoma, was identified as cryptopleurine (61) (67) is a close relative of tylocrebrine (68), from Tylophora crebrifolia (Asclepiadaceae), whose high activity against lymphoid leukaemia L-1210 in mice had been observed. ... 

The injection of cytosine (50-100 mg/kg) into the stomach of mice with lymphoid leukaemia prolonged life and reduced the leukocyte count. In some cases a haematological and clinical remission occurred. Uracil by itself worsened the leukaemia, although it sometimes had beneficial results in combination with cytosine [251]. Other studies have shown beneficial effects with solid tumours [252, 253-255]. Cytosine was reported to increase antibody formation in rabbits with an intact spleen [256]. 

When fludarabine phosphate and pentostatin were used in the treatment of chronic lymphoid leukaemia, 4 out of 6 patients de-... 

A single-centre reported topical cidofovir use in four cases of extensive molluscum contagiosum in immunocompromised children on chemotherapy for acute lymphoid leukaemia 1% cidofovir cream was used and no adverse reactions were reported [8 ]. 

Table 5. The following complexes have been found to be inactive (T/C < 125%) against ip. L1210 lymphoid leukaemia in mice (data supplied by the National Cancer Institute). The vehicle of administration and dose range tested (see footnote) are given in brackets.

CAH Chronic active hepatitis CALLA Common lymphoblastic leukaemia antigen CALX Conjunctival associated lymphoid tissue CaM Calmodulin cAMP Cyclic adenosine monophosphate also knomt as adenosine 3, 5 -phosphate CAM CeU adhesion molecule CAP57 Cationic protein from neutrophils CAT Catalase CatG Cathepsin G... 

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. 

B25. Brunning, R. D., Borowitz, M. J., Matutes, E., Head, D., Glandrin, G., and Swerdlow, S. H., Precursor B lymphoblastic leukaemia/lymphoblastic lymphoma (precursor B-cell acute lymphoblastic leukaemia). In World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues (E. S. laffe, N. L. Harris, H. Stein, and J. W. Vardiman, eds.), pp. 111-114. IARC Press, Lyon, 2001. 

Cancer is uncommon during the first two decades of life, but is nonetheless a substantial concern. In the United States, cancer is diagnosed in approximately 12 400 children and adolescents annually and is the most common cause of death from any kind of disease between 1 and 19 years of age. In the United States and other developed countries, lymphoid neoplasms (leukaemia, lymphoma) and cancers of the central nervous system are the most common paediatric malignancies. Other kinds of childhood tumours include embryonal tumours of the retina, sympathetic nervous system, kidney, and liver tumours of bone and soft connective tissues and certain gonadal neoplasms. Different kinds of cancer (e.g. carcinomas of liver or thyroid) may predominate in children in parts of the world where specific environmental risk factors are more prevalent. 

Adrenocortical steroids are used for their action on specific cancers and also to treat some of the complications of cancer, e.g. hypercalcaemia, raised intracranial pressure. Their principal use is in cancer of the lymphoid tissues and blood. In leukaemias they may also reduce the incidence of complications such as haemolytic anaemia and thrombocytopenia. A glucocorticoid is preferred, e.g. prednisolone, as high doses are used and mineralocorticoid actions are not needed and cause fluid retention. 

Fig. 38.10 Chronic lymphatic leukaemia dense portal lymphoid cell infiltration (HE)...

Pentostam " sodium stibogluconate, pentostatin [ban, inn, usan) (deoxycoformycin DCF Nipent ) is a nucleoside ANTIBIOTIC produced by Streptomyces antibioticus and Aspergillus nidulans. It is a potent ENZYME INHIBITOR of adenosine deaminase. As a cytotoxic ANTICANCER AGENT it is used in chemotherapy to treat hairy cell leukaemia and lymphoid neoplasms. Pentothal thiopentone. 

Nioolle A, Proctor SJ, Summerfield GP. High dose chlorambucil in the treatment of lymphoid malignancies. Leukaemia Lymphoma, 2004, 45 271-275. 

Loutit J, Carr T. 1978. Lymphoid tumours and leukaemia induced in mice by bone-seeking radionuclides. Int J Radiat Biol Relat Stud Phys Chem Med 33 245-264. 

C11H16N4O4 268.272 Nucleoside antibiotic. Prod, by Strepto-myces antibioticus and Aspergillus nidulans. Potentiator, antineoplastic. Powerful adenosine deaminase inhibitor. Used to treat hairy cell leukaemia and lymphoid neoplasms. Nucleoside transporter substrate. Launched 1992 (US)... 

This alkylating agent acts on the haemo-poietic system, and particularly pronounced on the lymphoid series. It has been found to be effective in chronic lymphatic leukaemia, the non-Hodgkin lymphomas, Hodgkin s disease and in macroglobulinaemia. On the whole toxicity is slight, gastrointestinal intolerance is relatively uncommon and bone marrow depression is a late unavoidable complication. 

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