Leukemia (cont.)

Medical Treatment

Leukemia treatment falls into 2 categories: treatment to fight the cancer and treatment to relieve the symptoms of the disease and the side effects of the treatment (supportive care).

The most widely used anti-leukemic treatment is chemotherapy, that is, the use of powerful drugs to kill leukemia cells.

• Treatment usually involves combinations of chemotherapy.



• Depending on the medication, therapy may be administered by vein or by mouth.



• In some cases, chemotherapy can be given at the doctor's office or some may be taken at home; in other cases, the patient may have to stay in a hospital. This depends on which agents the patient is receiving along with his or her overall condition (sometimes measured in terms of "performance status").

Many people with leukemia have a semi-permanent intravenous (IV) line placed in the upper chest, near the shoulder.

• A thin, plastic tube called a catheter is passed through the skin of the chest and inserted into a large vein. It is held in place, usually for the planned duration or therapy, with a few stitches, which makes it possible to use the same vein on numerous occasions without worry about the intravenous line being pulled out. The line is often burrowed under the skin. 

People who have leukemia in their cerebrospinal fluid, or who are at high risk of having leukemic cells migrate to the spinal fluid, receive chemotherapy directly into the cerebrospinal canal. This is known as intrathecal chemotherapy.

• Intrathecal chemotherapy is necessary because drugs given via IV do not sufficiently penetrate into the cerebrospinal fluid or brain and, thus, cannot kill leukemia cells there. Insufficient penetration of drugs into the cerebrospinal fluid results in uncontrolled growth of leukemic cells in the cerebrospinal fluid. Sometimes the therapy is inserted into a sac placed in one of the larger fluid-filled areas of the brain, a ventricle. The sac is known as an Ommaya reservoir, so named after its developer. 



• The reservoir stays in place for the duration of the treatment.

Chemotherapy kills cells or stops them from reproducing. Chemotherapy also kills rapidly growing healthy cells, accounting for many of the side effects of therapy.

• The exact side effects depend on the particular agent or agents administered to the patient, and the severity of side effects depends on the doses given and the patient's tolerance.



• Chemotherapy has its most severe effects on the bone marrow, the hair follicles, and the digestive system (from the mouth to the anus). These are the areas of the body where cells reproduce and replace themselves most quickly. Occasionally, the fingernails and toenails may splinter, crack, develop deep ridges, or stop growing.



• Common side effects of chemotherapy include nausea and vomiting, diarrhea, hair loss, and irritation of the esophagus (the tube through which food passes from the mouth to the stomach).



• Because chemotherapy kills normal blood cells, it can have some of the same effects as the leukemia itself: infections, anemia, and bleeding problems. Therefore, treatment of a patient with leukemia may involve the use of antibiotics and other anti-infective agents, red blood cell and platelet transfusions, and periodic injections to help increase the production of healthy red blood cells.

Newer agents are being developed that target leukemia cells and only minimally affecting healthy cells.

• These agents greatly reduce the severity of side effects.



• Imatinib (Gleevec), an agent used in the treatment of CML, is an example of such a chemotherapeutic drug.

Chemotherapy is usually given in cycles.

• Each cycle consists of intensive treatment over several days followed by a few weeks without treatment for rest and recovery from side effects caused by the chemotherapy, particularly anemia and low white blood cells. The sequence is then repeated.



• Chemotherapy regimens may be administered for 2-6 cycles, depending on subtype of leukemia and risk factors involved.



• In accordance with particular treatment regimens, bone marrow exams may be carried out prior to each cycle of chemotherapy. After completion of treatment, the patient is evaluated again to see the effect of the chemotherapy on the leukemia.

Hematologists and oncologists often refer to phases of chemotherapy. Only in certain types of leukemia are all 3 phases used.

• Induction: The purpose of this first phase is to kill as many leukemia cells as possible and bring about a remission.



• Consolidation: In this phase, the goal is to seek out and kill the residual leukemia cells not killed by induction. Often, these cells are not detectable, but they are assumed to be still present.



• Maintenance: The third phase is used to keep numbers of leukemia cells low, that is, to keep the disease in remission. The doses of chemotherapy are not as high as in the first 2 phases. This phase can last as long as 2 years.

The fundamental goal of chemotherapy is to cure the patient. Cure means that blood tests and bone marrow biopsy show no evidence of leukemia and the leukemia does not come back (relapse) over time. Only time can determine whether a remission (with no evidence of disease) will lead to disease-free survival (cure). In effect, remission may be short-lived, thereby requiring administration of new, previously unseen therapy. Results of this approach, often referred to as second-line therapy, are rarely curative. Stem cell transplant, if available, has the best chance of a second-line therapy cure.

Biological drug therapy: This type of therapy uses biological drugs that act similarly to the body's natural immune system, such as monoclonal antibodies, interferon, or interleukins.

• Biological therapy consists of proteins like those produced naturally by the body's immune system to promote the body's innate ability to fight cancer.



• Some people with chronic lymphocytic leukemia or acute myelogenous leukemia receive a monoclonal antibody. This is an antibody specifically designed to fight their type of leukemia cells.



• Some people with chronic myelogenous leukemia receive injections of interferon, a protein produced by some of the body's lymphocytes, which on occasion may slow the growth of leukemia cells but which has many unpleasant side effects.

Radiation therapy: Radiotherapy is another treatment occasionally used in some types of leukemia.

• A high-energy beam is targeted at an organ, such as the brain, bones, or spleen, where large numbers of leukemia cells have collected. The radiation kills these cells.



• Radiation to the brain can have negative long-term effects on some people, especially children. It has been linked to learning or thinking problems later in life. For this reason, radiation to the brain is carefully calibrated and used only when absolutely required.

Stem cell transplantation: This is a treatment that allows use of very high doses of chemotherapy along with total body irradiation in order to kill the leukemic cells.

• At the completion of high-dose (lethal) therapy, the patient's immune system is essentially depleted, and the patient is at high risk of developing serious life-threatening infections. Accordingly, these patients are treated in specially designed, sterile, air-filtered marrow transplant rooms.



• Immediately upon completion of the high-dose therapy, stem cells from a healthy, complete blood cell matched donor, usually a sibling or less commonly a parent, are transplanted into a vein whereupon they migrate to the marrow where they grow and multiply before entering the circulation, a process that may take 2-3 weeks to be completed. On rare occasions, when a donor is not available, one's own marrow cells, usually pretreated in order to remove residual, but otherwise unseen, leukemic cells, are infused. This approach is far less successful than the use of matched donor cells.



• If a patient receives stem cells from a matched donor, the type of stem cell transplant is called allogeneic. If the patient’s own stem cells are reintroduced back into the patient following high dose therapy, the infusion is called autologous. Marrow or stem cells from an identical twin is referred to as syngeneic.

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