Many persons with acute lymphocytic leukemia (ALL) have a good chance for remission, or freedom from the signs and symptoms of cancer, with the current standard treatments. However, some persons have risk factors for not doing as well as others. In particular, an abnormal chromosome (called the

Philadelphia chromosome) found in the leukemia cells of some individuals, indicates that the standard treatments may not be as successful as for those without the abnormal Philadelphia chromosome. Researchers in Houston and Chicago now say that more intensive chemotherapy may improve the survival time for persons with ALL.

Acute lymphocytic leukemia, also called

acute lymphoblastic leukemia, is a cancer of the lymph system and bone marrow. The bone marrow (and circulating blood) contains early blood-forming cells, called

stem cells, which grow and mature into the 3 blood cell types: white blood cells (protect the body from infection), red blood cells (carry oxygen to the tissues), and platelets (help the blood to clot). In the case of ALL, the early immature white blood cells, called

lymphocytes, multiply rapidly and uncontrollably. Not only can this excess of lymphocytes cause swelling in the lymph tissues, but they can also crowd out other important blood cells made by the marrow, such as red blood cells and platelets, preventing these cells from doing their jobs properly.

Many treatment options are being studied for ALL, including new chemotherapy drugs, new ways to deliver chemotherapy (for example, directly to the brain and spine because leukemia can recur there), and new ways to use higher doses of chemotherapy in combination with stem cell transplantation or biologic therapies. Higher doses of chemotherapy (called

dose-intensive or

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high-dose chemotherapy) can kill more leukemia cells than standard doses of chemotherapy; however, they can also damage healthy cells, especially the young stem cells in the bone marrow. For this reason, a procedure called a

stem cell transplantation may be used in combination with high-dose chemotherapy and/or radiation therapy to “rescue” the bone marrow and enhance the production of new blood cells. In the case of an

allogeneic stem cell transplantation, stem cells are collected from the blood or bone marrow of a donor, are frozen, and then infused into the patient after he or she has undergone high-dose chemotherapy to kill the leukemia cells. This procedure replaces the patient’s own stem cells, which have been destroyed by the high-dose chemotherapy, thereby allowing more rapid recovery and production of the red blood cells, white blood cells, and platelets that the body needs. Alternatively, biologic therapies, such as Neupogen®, may sometimes be used to help speed up recovery from chemotherapy-related low blood counts.

Researchers treated 204 adults who had newly diagnosed ALL with an intravenous, high-dose 6-drug chemotherapy combination. The patients received 8 cycles of intensive chemotherapy, with injections of chemotherapy into the spinal fluid to prevent recurrences in the brain, followed by an injection of Neupogen to enhance blood cell recovery. If a stem cell donor was available, patients whose leukemia cells contained the Philadelphia chromosome

also underwent an allogeneic stem cell transplantation. Otherwise, these patients received followup chemotherapy with the drug cytarabine as well as biologic therapy with interferon-alfa, to maintain their responses. The results show that 91% of patients had a complete remission, and 6% died of complications from treatment. The 5-year survival without any disease was 39%. However, persons 60 years and older had a 3-year survival rate of only 25%. Overall, the response to this intensive therapy was superior to that of previously studied regimens, apparently increasing the complete remission rate from 75% to 91%, and the 5-year survival rate from 21% to 39%.

These researchers concluded that this intensive regimen was more effective in terms of response rate and survival time than a previously studied less intensive regimen; however, further investigation to compare these regimens directly is needed. In addition, further study to develop better treatments for persons with ALL who are at risk for a poor outcome is needed. Persons who have ALL with the Philadelphia chromosome or other risk factors may wish to talk with their doctor about the risks and benefits of participating in a clinical trial in which other new treatments are being studied. (

Journal of Clinical Oncology, Vol 18, No 3, pp 547-561, 2000)

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