Leukemia

Leukemia means too many white cells. The normal white blood count is between four and ten thousand per cubic millimeter of blood. There are two types of white cells; neutrophils and lymphocytes. There are two general types of leukemia; acute, connoting rapidly growing and chronic, meaning slowly growing. Untreated acute leukemia can kill in six weeks; untreated chronic causes no symptoms for years. Chronic Myelogenous Leukemia Chronic Lymphocytic Leukemia Chronic myelogenous leukemia evolves when a clone of neutrophils expands in an uncontrolled fashion. Chronic lymphocytic leukemia occurs when the lymphocytes become malignant and expand explosively. Chronic Myelogenous Leukemia The cause of this disease is unknown. It usually occurs in either sex in the mid fifties, though it can occur earlier. It is diagnosed by doing a simple blood test where the neutrophil count can be observed to be between twenty to two hundred thousand cells per drop of blood. Since the disease does not cause any symptoms –no pain, no fever -- the patient may have had the disease for years before it is diagnosed. The Evolution Of Disease The disease starts when a bone marrow myeloblast cell (the precursor stem-cell of the neutrophil) is damaged either by a virus, a chemical or natural mutation during cell division. Cells divide after they have duplicated their total quantity of nuclear material and then precipitate into twenty-six different chromosomes. At cell division, the twenty-six chromosomes have doubled to fifty-two and then divide into two cells containing twenty-six chromosomes each. Myelogenous leukemia evolves, when the chromosomes go through a chaotic division of chromosomes and one piece of Chromosome Nine becomes attached to chromosome Twenty-two and forms a new hybrid chromosome. This is called the Philadelphia chromosome, after the city where it was discovered. At the point where these two chromosomes form a union, a new gene, called the Bcr-Abl, is created. The product of this gene is a protein called tyrosine kinase, which promotes rapid cell growth. It stimulates that clone of "Philadelphia" myeloblasts to grow and maturate and thus a new generation of neutrophils evolves that is different and distinct from the original normal clone of white cells. The Three Phases of Chronic Myelogenous Leukemia Chronic myelogenous leukemia starts from a single cell and grows into a population of billions. It has three phases. During the chronic phase, the cells pack the bone marrow first; then the cells spill over into the blood and the white blood count rises. Later the spleen, the lymph nodes and sometimes the liver become packed with these "Philadelphia" neutrophils. The disease remains in this chronic asymptomatic phase for two to three years before it starts to change into a more aggressive disease. The intermediate phase lasts between six to twelve months and then acute leukemia evolves. During this phase, the disease is beginning to dedifferentiate into a more rapidly growing disease. During the chronic phase, the myeloblasts mature into almost normal neutrophils; during the acute phase, maturation ceases and the myeloblasts proliferate, without maturating, and fill the body with immature, useless cells that interfere both with the immune system and the production of vital blood cells, causing the patient, if untreated, to die of either infection or bleeding. The Treatment Treatment entails of selectively getting rid of the "Philadelphia" clone of cells. This used to be done using a drug called Hydrea and Interferon. But now a new drug has come along that makes this disease curable. It is called Imitinib Myselate. It inhibits the Bcr-Abl tyrosine kinase and puts it out of action so the "Philadelphia" clone dies off. Relapses have occurred but with the addition of the antibiotic tetracycline, remissions can be obtained. Imitinib Myselate is a tablet and has very few side effects other than its cost. The trade name is Gleevec. The production of these new drugs is taking the "scare" out of the word Leukemia. If you wish to know more about this disease or the drugs used to treat it, call my office for an appointment and I will be happy to discuss, clarify and successfully manage your disease. Chronic Lymphocytic Leukemia This is a malignancy of the immune system and those who have it have a weakened immune system. It is a disease of older people; sixty-five years or more. It is rare to see it in a young person but it can occur. The disease evolves when a clone of lymphocytes goes through a mutation and begins to grow in an uncontrolled fashion producing billions and billions of lymphocytes. Lymphocytes are small nuclear-rich cells that fill the bone marrow and then spill over into the blood. While circulating in the blood, many cells are precipitated in the lymph nodes, in the spleen and liver causing these to enlarge. The rapid growth of these cells goes unnoticed by the patient and when a diagnosis is made, the disease is usually advanced. Now-a-days, because patients have blood counts for many different reasons, chronic leukemia is being picked up very early and is much easier to control. The Nature of the Leukemic cells There are two different types of lymphocytes, named B-Cells and T-Cells. (For a description of these cells, go to the page on Cancer and The Immune System) Most chronic lymphatic leukemias are expansions of the B-Cells; very small percentages are T-Cells leukemias. Since B-Cells are producers of anti-bodies, they can usually be differenciated by the type of anti-body they produce. The B-Cells also have different antigens on their cell wall, which helps identify them. Different types of B-cell leukemias respond to different types of Anti-Sense drugs. (See the Page on Anti-sense drugs) Bcl-2 This type of leukemia evolves because the B-Cells go through a mutation after which the lymphocytes produce a protein called Bcl-2. Apoptosis is the natural death program that is programmed into the genome of all cells, right from the time of their birth. By bypassing apoptosis, the lymphocytes cannot. Some will remain in a dormant state while others keep proliferating so a large population of cells grows larger. First they occupy the marrow, then they filling up the lymph nodes, then the spleen and even the liver and many other organs become infiltrated with these small eternal cells. So patients, with advanced disease, present at the doctors office, they have large livers and spleens and quite often are anemic with low platelet counts because the marrow malfunctions due to the invasion of lymphocytes. While all this is going on, patients remain without symptoms until they become anemic and tire easily. The Treatment Chronic lymphatic leukemia is now very easy to treat. Since it is a slowly growing disease, many patients can be observed, without treatment, for a period of time. Treatment is not always needed right away. In older patients, many of them will have other diseases that are more life treating than their leukemias and will not need to be treated. If this disease is diagnosed in a very early phase, it can be observed for a while so its normal biological behavior can be monitored. It is treated when the disease is observed to be advancing. If the white blood count continues to rise, or if the patient notices that the lymph nodes are getting larger; if the hemoglobin level or the platelet count begins to drop. Remissions can be achieved now with combinations of drugs called Fludaramine and Cytoxan. Both these drugs kill lymphocytes. However they will weaken the immune system because they kill good lymphocytes as well as bad. So patients on these drugs must be watched for infections, especially slowly involving infections like tuberculosis, pneumocystis, coccidiomycosis, and legionaire’s disease. Rituxan is another drug that can be used to treat this type of leukemia. Rituxan is a monoclonal antibody that is preprogrammed to hit a target that sits on the wall of most lymphatic leukemia cells. One plan of treatment is to reduce the population of lymphocytes with Fludaramine and Cytoxan and then give Rituxan to eradicate any residual leukemia cells. By doing this, it is hope to get a higher remission rate. Another drugs, not yet on the market, called Genasense. This drug inhibits the expression of Bcl-2. Bcl-2 prevents cells from going to Apoptosis and if Bcl-2 is missing, due to Genasense, then the leukemic cells will die, helping to increase the remission and cure rate of this disease. Patients with chronic lymphatic leukemia have an increased risk of developing other malignancies during their lifetime so constant vigilance is necessary. Monitoring for polyps in the colon or spots in the lungs for smokers should be done. The production of all these new drugs is taking the scare out of the word "Leukemia". If you wish to know more about this disease or the drugs used to treat it, call my office for an appointment and I will be happy to discuss, clarify or manage your condition.