Leukemia

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Treatment

Treatment of leukemia depends on the type and extent of the disease and is tailored to each individual patient. In general, chemotherapy—the use of drugs that kill rapidly dividing cells—is the mainstay of treatment for both acute and chronic leukemias. In acute leukemias, chemotherapy is very intensive and uses several drugs, either simultaneously or sequentially, in order to kill as many leukemic cells as possible. Antibiotics and transfusions of red cells and platelets help sustain patients whose blood counts are dangerously low because they are receiving intensive chemotherapy.

Sometimes radiation is used to shrink collections of leukemic cells that accumulate in various parts of the body, such as on the lining of the brain and spinal cord in acute lymphocytic leukemia, or within lymph nodes in chronic lymphocytic leukemia. If left untreated, collections of cells on the lining of the brain and spinal cord can cause headache, blurred vision, and confusion, and elsewhere in the body can cause swelling and tenderness of the affected area.

Particularly in young patients, if doctors determine that chemotherapy alone is not likely to be successful or if patients relapse after chemotherapy, allogeneic (genetically different) stem cell transplantation may be performed. In this procedure, very intensive total body radiation or very high doses of chemotherapy or both are used. The chemotherapy and radiation are designed to destroy all the leukemic cells in a patient’s body; however, this treatment also destroys the blood-forming system in the patient’s bone marrow. For this reason, healthy stem cells, the cells in bone marrow that enable long-term formation of blood, must then be infused into a patient to replenish the blood-forming system. The stem cells must come from an immunologically matched donor, usually a sibling, but if a sibling match is unavailable, occasionally an unrelated donor may be sought. The latter can be identified from a database of volunteer donors. These databases can be searched for a person with an identical or very close tissue type match. Formerly, stem cells could only be transplanted from the bone marrow of the donor. The procedure was known as bone marrow transplantation. Recent advances now make it possible to recover stem cells from blood, or from the placenta and umbilical cord blood (“cord blood”) after delivery of a newborn, making the transplant procedure much simpler and less risky for the donor. Cord-blood stem cells are frozen, kept in a “bank,” and can be used later for a patient in need. The number of stem cells in these samples may be insufficient for larger adults and are used most commonly for children or smaller adults who require a transplant and are in need of a matched, unrelated donor.

An unexpected effect of allogeneic stem cell transplantation is what is known as graft-versus-leukemia effect. The immune cells of the donor recognize minor tissue type antigens (the proteins that produce antibodies) that do not match the recipient’s. These donor immune cells attack the recipient’s tissues, including both leukemia cells and normal tissues. The attack against the recipient’s normal tissues is referred to as graft-versus-host disease. This attack can be acute or chronic, and very mild or very severe. It is a serious, unwanted complication of allogeneic stem cell transplantation. Graft-versus-leukemia-cells, on the other hand, is a desirable effect and is responsible in part for some of the beneficial effects of transplantation, especially in patients who received transplants to treat acute or chronic myelocytic leukemia.

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Transplantation is most effective in children and young adults; in older adults it is often too hazardous a procedure to apply. An approach called non-myeloablative stem cell transplantation is being tested in older patients. Here very mild pretreatment with chemotherapy or irradiation is used, while anti-immune therapy is relied on to prevent the recipient’s immune system from rejecting the donor’s stem cells. The graft-versus-leukemia effect is relied on as a substitute for the very intensive therapy given before a standard transplant for leukemia.

Immunotherapy is a promising new approach to treating leukemia. In this technique, highly specific molecules known as monoclonal antibodies are manufactured in the laboratory to target molecules on the surface of leukemic cells. The antibodies themselves may kill the leukemic cells, or a radioactive substance or cell toxin attached to the antibodies may kill the leukemic cells, when injected intravenously into a patient. This method provides a convenient means of delivering the radioactive or toxic substance directly to leukemic cells, where it may kill these cells with minimal effect on healthy cells.

The goal in treating acute leukemias is to kill enough leukemic cells to produce a remission, meaning that the production of healthy blood cells is no longer suppressed, blood cell counts return to normal, and the patient’s symptoms diminish. At that stage, further therapy is used to try to prolong remission or achieve a cure. About 80 percent of children with acute lymphocytic leukemia are cured. Cure rates in acute myelocytic leukemia are estimated to be about 40 percent in children but are much lower in adults depending on their age. Since most patients are over 65 years when they develop the disease, cures are infrequent.

In the chronic leukemias, cures are very infrequent, but today’s chemotherapy regimens have increased the average survival in these patients from about three years to more than six years. Chronic lymphocytic leukemia in its most indolent form may not require treatment and may not progress or be a serious health consequence for the patient. In patients with active or progressive disease, several new drugs and types of monoclonal antibodies are available to treat the disease. In chronic myelocytic leukemia, a dramatic advance in therapy involves the introduction of a drug that specifically targets the leukemia-causing change in the marrow cell. The introduction of this treatment has been projected to increase survival to more than a decade on average. Young patients with the disease who have an appropriate stem cell donor can be cured with stem cell transplantation.