Alkylating agents are important because they interfere with the growth and reproduction of cells, disrupting their replication. This CYTOTOXIC property is used to retard the division and growth of cancer cells, and alkylating drugs are widely used in the chemotherapy of malignant tumours – often in conjunction with surgery and sometimes with radiotherapy. Unfortunately, troublesome side-effects occur, such as: damage to veins when the drug is given intravenously, with resultant leakage into adjacent tissues; impaired kidney function due to the formation of URIC ACID crystals; nausea and vomiting; ALOPECIA (hair loss); suppression of BONE MARROW activity (production of blood cells); and adverse effects on reproductive function, including TERATOGENESIS. Indeed, cytotoxic drugs must not be given in pregnancy, especially during the ?rst three months. Prolonged use of alkylating drugs, especially when accompanying radiotherapy, is also associated with a sign?cant rise in the incidence of acute non-lymphocytic LEUKAEMIA. Among the dozen or so alkylating drugs in use are CYCLOPHOSPHAMIDE, CHLORAMBUCIL, MELPHALAN, BUSULFAN and THIOTEPA. (See also CHEMOTHERAPY.)... alkylating agents
According to the type of cells that predominate, leukaemia may be classi?ed as acute or chronic lymphoblastic leukaemia or myeloid leukaemia. Acute lymphoblastic leukaemia (ALL) is mostly a disease of childhood and is rare after the age of 25. Acute myeloid leukaemia is most common in children and young adults, but may occur at any age. Chronic lymphatic leukaemia occurs at any age between 35 and 80, most commonly in the 60s, and is twice as common in men as in women. Chronic myeloid leukaemia is rare before the age of 25, and most common between the ages of 30 and 65; men and women are equally affected. Around 2,500 patients with acute leukaemia are diagnosed in the United Kingdom, with a similar number annually diagnosed with chronic leukaemia.
Cause Both types of acute leukaemia seem to arise from a MUTATION in a single white cell. The genetically changed cell then goes through an uncontrolled succession of divisions resulting in many millions of abnormal white cells in the blood, bone marrow and other tissues. Possible causes are virus infection, chemical exposure, radiation and genetic background. The cause of chronic lymphocytic leukaemia is not known; the chronic myeloid version may have a genetic background.
Symptoms In acute cases the patient is pale due to anaemia, may have a purpuric rash due to lack of platelets, and may have enlarged lymphatic glands and spleen. The temperature is raised, and the condition may be mistaken for an acute infection (or may ?rst become apparent because the patient develops a severe infection due to a lack of normal white blood cells).
In the chronic type of the disease the onset is gradual, and the ?rst symptoms which occasion discomfort are either swelling of the abdomen and shortness of breath, due to painless enlargement of the spleen; or the enlargement of glands in the neck, armpits and elsewhere; or the pallor, palpitation, and other symptoms of anaemia which often accompany leukaemia. Occasional bleeding from the nose, stomach, gums or bowels may occur, and may be severe. Generally, there is a slight fever.
When the blood is examined microscopically, not only is there an enormous increase in the number of white cells, which may be multiplied 30- or 60-fold, but various immature forms are also found. In the lymphatic form of the disease, most white cells resemble lymphocytes, which, in healthy blood, are present only in small numbers. In the myeloid form, myelocytes, or large immature cells from the bone marrow, which are never present in healthy blood, appear in large numbers, and there may also be large numbers of immature, nucleated erythrocytes.
Treatment This varies according to the type of leukaemia and to the particular condition of the patient. Excellent results are being obtained in the control of ALL using blood transfusions, CHEMOTHERAPY, RADIOTHERAPY and bone-marrow TRANSPLANTATION. In the case of acute leukaemia, the drugs now being used include MERCAPTOPURINE, METHOTREXATE and CYCLOPHOSPHAMIDE. Blood transfusion and CORTICOSTEROIDS play an important part in controlling the condition during the period before a response to chemotherapy can be expected. Chemotherapy has almost completely replaced radiotherapy in the treatment of chronic leukaemia. For the myeloid form, BUSULFAN is the most widely used drug, replaced by hydroxyurea, mercaptopurine, or one of the nitrogen mustard (see NITROGEN MUSTARDS) derivatives in the later stages of the disease. For the lymphatic form, the drugs used are CHLORAMBUCIL, CYCLOPHOSPHAMIDE, and the nitrogen mustard derivatives.
Prognosis Although there is still no guaranteed cure, the outlook in both acute and chronic leukaemia has greatly improved – particularly for the acute form of the disease. Between 70 and 80 per cent of children with acute lymphoblastic leukaemia may be cured; between 20 and 50 per cent of those with acute myeloid leukaemia now have much-improved survival rates. Prognosis of patients with chronic lymphocytic leukaemia is often good, depending on early diagnosis.... leukaemia
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