The treatment of acute lymphocytic leukemia is directed first at trying to destroy the leukemic cells in the bone marrow and lymphoid systems, and secondly destroying any leukemia cells that are left in so-called ‘sanctuary sites’. These sanctuary sites are body parts that include the testes, ovaries, brain and spinal cord—where leukemic cells are found but where drugs are difficult to execute. Leukemic cells can reside in sanctuaries, in a resting state for prolonged periods prior to beginning to proliferate again and causing a clinical relapse.

The treatment of acute lymphocytic leukemia has improved substantially in the past 40 years, particularly in children, whom have an improved successful cure rate of 70—75%. The success rate for adults has been considerably less but both the remission rates and probability of cure do appear to be rising.

The conventional approach is a treatment plan in three phases: remissions induction, consolidation and maintenance.

Remission induction

Remission induction treatments usually involve the use of three or four drugs, and commonly results in complete remission—which is defined as the absence of detectable leukemic cells in the blood and bone marrow. Complete remission is usually achieved in more that 90% of children and 60% of adults.

Consolidation

Once complete remission is achieved, several extra courses of the same drugs are taken to minimize the occurrence of reoccurrence of the disease. This is known as consolidation. The most common drug used in the first and second phases of treatment are vincristine, daunorubicin (or its equivalent), L-asparaginase, and prednisolone. Prednisolone is taken by mouth while the others are injected.

Vincristine is a potent cancer chemotherapeutic drug that works by biding leukemic cells to the proteins tubulin and preventing cellular division. Tubulin forms fibers that help cells divide in an orderly fashion. Since all leukemic cells irregularly divide, vinvristine is given weekly in the hope that eventually all the leukemic cells will be affected. Vincristine can cause constipation and stomach cramps, and if given in excess can lead to temporary paralysis of the bowel or of certain nerves—resulting in muscle weakness which may result in foot-drop, wrist-drop, and facial paralysis.

Daunorubicin is an anthracycline that acts directly by inhibiting cell growth by blocking the action of the enyzyme topoisomerease II. Anthracycline inhibit powerful enzyme prevent repair of broken DNA strands, resulting in cell death. It gives urine a harmless reddish color that can persist for 24-48 hours. The drug has several common side-effects including nausea, vomiting, and bone marrow depression—an abnormal condition of the bone marrow in which it’s unable to produce normal amounts of red blood cells. On rare occasions it can also cause heart disease and damage, particularly in high doses.

In recent years, new generation anthracycline drugs have become available such as epirubicin and idarubicin. These new drugs seem safer to the heart and idarubicin also appear to be more potent in killing leukemic cells. An increasing number of specialists now use idarubicin instead of daunorubicin. Mitozantrone, another experimental drug, may also have fewer toxic effects than daunorubicin.

All anthracyclines can produce hair loss after the first week of injections, and in most cases the hair grows back after 1-2 months after the drug is stopped taken. Often the new hair is curlier and of a lighter shade than before.

L-asparaginase works by depriving cancer cells of an essential amino acid called asparagine. It can produce allergic reactions—inflammation of the liver and pancreas. These reactions can be quite serious and can cause difficulty breathing, puffy face, and/or rashes. Other side-effects can include tiredness, loss of appetite, stomach cramps, and an increase in blood sugar. This can stimulate diabetes, frequent urination, and increased thirst.

Prednisolone is an anabolic steroid, which is usually taken by mouth causes stomach problems (particularly superficial ulcers) and high blood pressure due to water retention. In rare cases, steroids can cause psychiatric difficulties, particularly depression and other mood alterations. In addition, it can also cause muscle cramps, blurred vision, and difficulty sleeping. However, its beneficial action is rapid and has been an exceptional drug in acutely leukemic patients. Side-effects disappear upon discontinuing the drug.

In a typical treatment plan, vincristine is administered by intravenous (IV) each week for 5-6 weeks. Prednisolone each day for 3-4 weeks, daunorubicin each day for the first 3 days of the treatment cycle, and L-asparaginase each day for 10 days, beginning on day 22 of the treatment cycle.

Most doctors believe the rate of at which leukemic blast cells are killed in blood and bone marrow is an important prognostic indicator. Remission within the first 2 weeks of commencing induction therapy predicts a better outcome. Once induction treatment has been complete and normal blood counts have been restored, therapy directed at the sanctuary sites will begin.

The next phase of the treatment plan is consolidation, its main objective being to minimize tumor load. A variety of cytotoxic drugs are used including cyclophosphamide, teniposide, Ara-C, daunorubicin, etoposide, and prednisolone.

Maintenance

The final phase of the treatment is maintenance, which usually starts soon after completing CNS and consolidation treatment, and is continued for 2-3 years on an outpatient basis. The role of maintenance therapy has been fully established in both children and adults with acute lymphocytic leukemia. The intensity of maintenance therapy should be such that both bone marrow and the immune system are suppressed to avoid failure.

The drugs most often used for maintenance are 6-mercaptopurine and methotrexate, both taken orally. 6-Mercaptoputine acts by interfering the synthesis of DNA building blocks and is relatively free of any side-effects.

Methotrexate works by preventing cells from making new DNA by blocking the enzyte dihydrofolate reductase, and is absorbed and excreted rapidly by normally functioning kidneys; in patients with impaired kidneys it is very poorly excreted, resulting in higher blood levels of the drug. Side-effects range from nausea and vomiting to ulcerations of the stomach.