Leukemia Chemotherapy.

The goal of chemotherapy is to give a sufficient amount of drugs to destroy nearly all cells, both normal and abnormal, that are contained in the patient's bone marrow. This may require a combination of two to five drugs, each possibly attacking the cancer cells in a different way. Since leukemia cells are known to divide more slowly than their normal counterparts, then theoretically, if almost all the marrow is destroyed, the healthy cells, which grow and regenerate faster, are more likely to re-populate the marrow.

The schedules of chemotherapeutic drug administration have been worked out over years through a combination of theory and trial and error.

They are designed to take maximum advantage of the susceptibilities and re growth cycles of leukemia cells. The proportion of normal cells will then increase with each cycle of chemotherapy in a successfully treated patient. The goal is to induce a complete remission, the state in which all blood tests, including bone marrow examination, have returned to normal. A complete remission is defined as finding no evidence in laboratory tests that the patient has or has ever had leukemia. Depending on the particular category of leukemia, 50 to 90 percent or more of patients will achieve a complete remission.

Some remissions are not as successful: the patient feels better; the pattern and number of cells in the blood have returned to normal; but the bone marrow, although improved, remains abnormal. The exact degree of these partial remissions is not easily ascertained, since abnormal leukemia cells can closely resemble their normal but immature counterparts. If a remission is not obtained with the usual drugs, the oncologist will try to induce it with second-line or experimental drugs. Patients who do not enter into a period of complete or partial remission do not have as good a prognosis.

Once a complete or partial remission has been induced, the patient will be placed on maintenance chemotherapy, with the dose, schedule, and duration tailored to the patient's specific diagnosis and ability to tolerate chemotherapy. Depending on the timing and specific strategy chosen, these treatments may be termed consolidation, intensification, or reinforcement. Maintenance therapy may be continued for as long as four years in apparently cured patients, especially children. Since relapse after five years of complete remission is rare, patients whose remission surpasses this may be considered cured. On the other hand, patients who do not obtain a complete remission lasting at least four years will almost undoubtedly have a relapse.

Patients who experience a relapse will receive more chemotherapy, possibly with the same drugs that induced the original remission. Repeated relapses generally signal a progressively poorer response to therapy, with remissions becoming shorter and shorter and an effective strategy and drug regimen more difficult to prescribe. Drug resistance on the part of leukemic cells is the fundamental problem. Although doctors do not know the cause of the resistance, they suspect that the chemotherapeutic agents destroy the sensitive cells and establish an environment that allows the resistant cells to flourish.

The major drugs used to treat leukemia are vincristine, methotrexate, G-mercaptopurine, cytosine arabinoside, busulfar chlorambucil, daunorubicin, 1-asparaginase, and prednisone. Most of these drugs have been used for at least ten years and oncologists have become familiar with their actions and side effects. Relatively few successful new agents have been developed during the last five to ten years except for s-azacytidine and M-amsa.

The side effects of chemotherapy necessitate hospitalization for almost all patients during the entire process of chemotherapy, until remission is induced. This stay may last six weeks or longer. The low white count induced by the drugs makes patients susceptible to infection, while the reduction in platelets predisposes to bleeding. Patients must be closely monitored, often with daily blood tests in case transfusions of red cells, white cells, platelets, gamma globulin, and clotting factors are needed.
Infection remains a serious problem, although the situation has vastly improved because of new, more powerful antibiotics. Gram-negative bacteria, especially pseudomonas and E. coli, are among the most common causes of infection. Fungal and viral infections also occur and are more difficult to treat. Antileukemic therapy can be complicated by problems other than infection and bleeding, such as cardiac toxicity (induced by daunorubicin), or nerve toxicity (induced by vincristine).

The first problem is not reversible on stopping the drug; the second is.
Some patients with chronic leukemia who require no or only mild chemotherapeutic treatment can, after the initial investigations are completed, be treated on an outpatient basis. Maintenance therapy after remission can usually be administered in the outpatient department of a hospital, in the hematologist-oncologist's office, or during relatively brief intermittent hospital stays.

The physical examination plays a relatively small role in the initial diagnosis and evaluation of a leukemia patient. It is hardly ever crucial to the diagnosis but must not be neglected, and should be performed at appropriate intervals to judge the effect of therapy and the regression or progression of the disease. Particular attention should be paid to the lymph nodes, pharynx, gums, eyes (for bleeding), and possible sites of infection such as the skin, mouth, vagina, and anus. This routine and brief inspection should be performed at almost every visit, especially if chemotherapy is being administered and the risk of infection by bacteria or fungi is increased. Changes in the size of the liver and spleen also should be noted.

Patients undergoing intense chemotherapy experience numerous side effects, since the drugs are highly toxic to both normal and cancerous tissue. Nausea and vomiting are almost universal, as is hair loss. Anti nausea drugs and timing of chemotherapy can help counter the nausea and vomiting. The hair loss is temporary, but distressing to most patients.

In most cases the patient will remain under the care of his or her internist or general practitioner while the oncologist concentrates on the anticancer chemotherapy. Continuing treatment can usually be given close to home but induction of remission should almost always be carried out in a major medical center. The potential problems and complications are too great to be managed at small community hospitals that are not equipped or experienced in this field.