Acute Lymphocytic Leukemia (ALL)

Adult Acute Lymphocytic Leukemia (also called acute lymphoblastic leukemia or ALL) is a disease in which too many infection-fighting white blood cells called lymphocytes are found in the blood and bone marrow. Lymphocytes are made by the bone marrow and by other organs of the lymph system.

Lymphocytes are found in the lymph which is a colorless, watery fluid present in the lymph vessels. The lymph vessels are part of the lymph system which is made up of thin tubes that branch, like blood vessels, into all parts of the body. Along the network of vessels are groups of small, bean-shaped organs called lymph nodes. Clusters of lymph nodes are found in the underarm, pelvis, neck, and abdomen. The spleen (an organ in the upper abdomen that makes lymphocytes and filters old blood cells from the blood), the thymus (a small organ beneath the breastbone), and the tonsils (an organ in the throat) are also part of the lymph system.

In ALL, the developing lymphocytes do not mature and become too numerous. These immature lymphocytes are then found in the blood and the bone marrow. They also collect in the lymph tissues and make them swell. Lymphocytes may crowd out other blood cells in the blood and bone marrow. If the bone marrow cannot make enough red blood cells to carry oxygen, then anemia may develop. If the bone marrow cannot make enough platelets to make the blood clot normally, the bleeding or bruising may develop more easily. The cancerous lymphocytes can also invade other organs, the spinal cord, and the brain.

Several years ago, an international conference of prominent hematologists/oncologists specializing in leukemia treatment and pathologists specializing in laboratory tests for blood disease diagnosis was held to decide upon the best system of classification of acute leukemias. This group of French, American, and British (FAB) doctors decided that acute leukemias should be divided into eight subtypes of AML and three subtypes of ALL.

The subclassification of the disease is important. Different types of therapy may be used and the likely course of the disease may be different. Additional features may be important in guiding the choice of therapy, including: abnormalities of chromosomes , the cell immunophenotype, the age and the general health of the patient, and others.

The original FAB system was based only on appearance of leukemic cells under the microscope after routine processing or cytochemical staining. More recently, doctors have found that cytogenetic studies, flow cytometry, and molecular genetic studies provide additional information that is sometimes useful in classification of acute leukemias and predicting the patient's prognosis.

French-American-British (FAB) Classification of ALL
FAB Subtype	Approximate % of adult ALL patients	Immunologic Type	Comments
L1	30%	T cell or pre-B cell
L2	65%	T cell or pre-B cell
L3	5%	B cell	Poor prognosis with standard therapy. Also called Burkitt’s type leukemia.

Most patients feel a loss of well-being. They tire more easily and may feel short of breath when physically active. They may have a pale complexion from anemia. Signs of bleeding because of a very low platelet count may be noticed. These include black- and-blue marks occurring for no reason or because of a minor injury, the appearance of pinhead-sized, red spots under the skin, called petechiae, or prolonged bleeding from minor cuts. Frequent minor infections of the skin or of the ear, slow healing of cuts, or discomfort in bones or joints may occur. In acute lymphocytic leukemia, the abnormal cells may collect in the brain or spinal cord (also called the central nervous system). The result may be headaches and vomiting. Leukemia cells can also collect in the lymphatic system, and lymph nodes may become enlarged.

If there are symptoms, please see your family doctor who may order blood tests to count the number of each of the different kinds of blood cells. If the results of the blood test are not normal, the doctor may order more blood tests. A bone marrow biopsy also may be done. During this test, a needle is inserted into a bone and a small amount of bone marrow is taken out and looked at under the microscope. The doctor can then tell what kind of leukemia the patient has and plan the best treatment.

Stage Explanation

There is no staging for ALL. Your choice of treatment depends on whether a patient has been treated before.

Untreated ALL means that no treatment has been given except to treat symptoms. There are too many white blood cells in the blood and bone marrow, and there may be other signs and symptoms of leukemia.

Remission means that treatment has been given and that the number of white blood cells and other blood cells in the blood and bone marrow is normal. There are no signs or symptoms of leukemia.

Recurrent disease means that the leukemia has come back after going into remission. Refractory disease means that the leukemia has failed to go into remission following treatment.

Treatment Options

There are treatments for all patients with ALL. The primary treatment of ALL is chemotherapy. Radiation therapy may be used in certain cases. Bone marrow transplantation is being studied in clinical trials.

This is the standard method of treatment in which anti-cancer drugs are administered to the patients. The dose is adjusted according to their WBC counts that is taken every 2-3 weeks. This form of treatment can reduce WBC counts, spleen size and other symptoms.

Prior to advent of chemotherapy, radiotherapy to spleen was the preferred treatment. Since chemotherapy yields better results, radiotherapy is generally not considered except for situations where spleen doesn't respond to chemotherapy.

Bone marrow transplantation is used to replace the patient's bone marrow with healthy bone marrow. First, all of the bone marrow in the body is destroyed with high doses of chemotherapy with or without radiation therapy. Healthy marrow is then taken from another person (a donor) whose tissue is the same as or almost the same as the patient's. The donor may be a twin (the best match), a brother or sister, or another person not related. The healthy marrow from the donor is given to the patient through a needle in the vein, and the marrow replaces the marrow that was destroyed. A bone marrow transplant using marrow from a relative or person not related to the patient is called an allogeneic bone marrow transplant.

Another type of bone marrow transplant, called autologous bone marrow transplant, is being tested in clinical trials. To do this type of transplant, bone marrow is taken from the patient and treated with drugs to kill any cancer cells. The marrow is then frozen to save it. The patient is given high-dose chemotherapy with or without radiation therapy to destroy all of the remaining marrow. The frozen marrow that was saved is then thawed and given back to the patient through a needle in a vein to replace the marrow that was destroyed.

Standard treatment may be considered because of its effectiveness in patients in past studies, or participation in a clinical trial may be considered. Most patients are not cured with standard therapy and some standard treatments may have more side effects than are desired.

This is the initial phase of specific treatment. The specific drugs used, the doses used, and the timing of their administration depend on several factors, including the patient's age, the features of the leukemia, and the general health of the patient. Several drugs are combined. Acute lymphocytic leukemia cells often collect in the lining of the spinal cord and brain, called the meninges. If not treated, the meninges can harbor leukemia cells, and relapse can occur in this site (meningeal leukemia). For this reason, treatment is also directed to those sites by injecting drugs into the spinal column, or irradiating the covering of the central nervous system using an X-ray treatment machine. Sometimes both forms of treatment are used. These areas of the body, which are less accessible to chemotherapy when given by mouth or in the vein, have been referred to as sanctuary sites.

In most patients, after several weeks normal blood cell production will return and transfusion of cells and antibiotics will no longer be needed. Blood cell counts gradually approach normal, well-being returns, and leukemia cells cannot be identified in blood or marrow. This is a remission. In this state, residual leukemia cells are inactive. They do not interfere with normal blood cell development but have the potential to regrow and cause a relapse of the leukemia. For this reason, additional therapy in the form of chemotherapy usually continues.

Since residual leukemia cells that cannot be detected by the blood or marrow examination remain after a remission, the optimal treatment of ALL requires additional intensive therapy after remission has been achieved. As in the induction phase, individual factors such as age of the patient, the ability to tolerate intensive treatment, cytogenetic findings, the availability of a stem cell donor, and others may influence the approach used. In most cases, post-remission chemotherapy also includes drugs not used during induction treatment .

Patients between the ages of approximately 1 and 50 years who are in remission and have an HLA-matched donor are candidates for allogeneic stem cell transplantation. The decision to do a transplant depends on the features of the leukemia, the age of the patient, and the patient's (or his or her family's) understanding of the potential benefits and risks.