Acute Lymphoblastic Leukemia
By Debbie Block
Summer Discovery Program: Exploring Careers in Medicine
Instructor: Steve Anisman
Summer, 1998
Acute lymphoblastic leukemia, also referred to as ALL, is a form of cancer usually found in children. Acute means that the disease is formed rapidly and that the symptoms appear suddenly, rather than over a long period of time as in chronic diseases. Lymphoblastic means that the blast cells of the lymphatic system are affected. ALL is a malignant disorder from the clonal proliferation of lymphoid precursors with arrested maturation. In other words, it is a blood dyscrasia and a form of cancer of the white blood cells in which many immature white blood cells are produced. The nuclei of the cells regenerate out of control. The white blood cells are overproduced and the cancerous cells tend to live longer than the normal cells. Therefore, the cancerous cells monopolize the body. The cancerous cells circulate through the entire body and can affect all of the organs. In the bone marrow, the leukemic cells interfere with the bone marrow's production of red blood cells and a certain type of white blood cells known as neutrophils. Neutrophils are mature white blood cells formed in the bone marrow and released into the blood. They make up 54- 65% of the total leukocytes.
Most of the body's blood cells are produced in the bone marrow, however, lymphocytes, or white blood cells, are produced in the spleen or in the lymph glands which are found in the neck, arm pits, groin, and many other body parts. Together with channels and ducts, which connect them and the spleen and lymph glands, they form the lymphatic system. ALL affects lymphocytes that are produced in the lymph glands. The cancerous cells overflow in the lymph glands. That is due to the fact that in a normal system, the rate of lymphocyte production is the same as the rate at which lymphocytes die. The difference between that and a body with leukemia is that in a body with leukemia, the rate at which the cancerous lymphocytes are produced is much greater than the rate at which lymphocytes die. Also, the cancerous cells' life expectancy is much longer than the life expectancy of normal cells.
In 70 to 75% of children with ALL, acquired clonal chromosome abnormalities can be detected in the spontaneously dividing blast cells at the time of the diagnosis. About half of those tend to be specific to the tumor type that is involved. Cell specificity means that there is a close correlation between the aberrations and the immunophenotype of the blasts. Structural abnormalities, mostly translocations and deletions involving specific break points, are in two thirds of the patients with abnormal karyotypes described to date.
The standard treatment of ALL consists of the following, differentiating according to the individual needs of each patient. Usually, anti- cancer and/or steroid drugs are consumed using a multi- drug schedule, along with radiation therapy. In most cases, this treatment causes major symptoms to disappear, also known as when a patient goes into remission after several weeks or so depending on the case. The child then returns home and tries to conduct as normal of a life as possible. Over the next year, the child comes in for frequent check ups and doses of drugs. If the symptoms reoccur, the most effective treatment is a bone marrow transplant. Chemotherapy, or drug treatment, cures approximately 70% of children who have ALL. Some patients may not survive because they are either over-treated or under-treated with chemotherapy. Allogenic bone marrow transplants (AlloBMTs) may cure patients who have ALL and never receive remission with chemotherapy.
A bone marrow transplant consists of destroying leukemic and healthy cells by radiation and drugs. Those are then replaced with healthy cells from a donor. The child is then kept in isolation to protect against infection. AlloBMTs work especially well if an identical twin is able to donate marrow. Blood marrow transplants provide disease- free survival rates 40- 70% in children with reoccurring ALL. Application is limited by lack of sibling donors. Only about 30% of all children who have ALL will have a suitable, matched sibling donor. Bone marrow transplants may be needed because there is no other possible life saving alternative. It is recommended that all family members of a patient who has ALL be tested for bone marrow compatibility as soon as the patient is diagnosed with ALL to save time if an AlloBMT is needed.
Thromboembolic events (TE) are very serious complications in the treatment of pediatric ALL that result in significant morbidity and occasional mortality. A thromboembolic event, or thromboembolism, is an obstruction of a vessel by a blood clot that has been transported to that place from a distant site by the blood stream. It can cause a cardiac arrest and it is strongly associated with the administration of a drug called L'aspariginase. Other Complications that often occur in patients who have ALL are hyperuricemia and acute renal failure.
More than fifteen different structural rearrangements are known in ALL. Pediatrics who have ALL without specific structural abnormalities are classified by the modal chromosome numbers which are diploid (46 chromosomes), psuedodiploid (46 with structural or numerical abnormalities), hyperdiploid (47- 50), and hyperdiploid B (greater than 50). To identify patients with greater than fifty chromosomes there are three methods. They are classical cytogenetic analysis, flow cytometry, and florescence in situ hybridization (FISH). A recently developed FISH technique, the so called comparative genomic hybridization (CGH) offers new possibility to determine all chromosome gains and losses in tissues unsuitable for traditional cytogenetic analysis. None of the current methods gives complete information about all genetic changes.
Abnormalities of chromosome 21 are the most frequent numerical abnormalities found in ALL. An extra chromosome 21 is the most frequent gain in ALL in the 330 cases collected at the third international workshop on chromosomes in leukemia. Down syndrome and Alzheimer Disease are also resulted from Chromosome 21 abnormalities. Alzheimer Disease is a condition found in elderly people in which they have gradual memory loss. Down Syndrome is acquired before birth in which the people who have it have some degree of mental retardation. It is the most common autosomal chromosomal anomality in the general population. The first case of acute leukemia in a child with Down Syndrome was reported in 1930. One person out of every 660 live births is born with Down Syndrome. One person out of every 2800 has acute leukemia before he or she is 15. Children with Down Syndrome have 10-15 times the risk of developing acute leukemia because of chromosome 21 abnormalities. There are approximately 14 fold increased incident of ALL in children with Down Syndrome. There are only a few differences in ALL between children with Down Syndrome and Children without Down Syndrome. The remission rates are very similar, although children with ALL whom have Down Syndrome tend to have less platelets and more favorable prognosis factors.
There are four major types of leukemia that are known. ALL is the most commonly detected type of leukemia. Acute myeloid leukemia (AML) is the other type of acute leukemia and also the second most common type. The two other types are chronic lymphoblastic leukemia and FIND OTHER TYPE. Lymphomas are also types of cancer that are similar to ALL because they affect the lymphatic system.
There are many experiments to find a cure to ALL. To do this, first scientists must conduct experiments to figure out what causes someone to have ALL. Countries all over the world are spending a lot of money on experiments, all of which, so far, are unsuccessful. There are many groups of people who hold conferences to discuss results of their experiments and possibilities of causes and cures. Some of these groups are Pediatric Oncology Group (POG), Children's Cancer and Leukemia Study Group (CCLSG) and International Society of Pediatric Oncology (ISOP). Most research that is conducted has something to do with drug therapy.