Celebrity / NYJSM Consult / Melissa Baker

Melissa Baker consults Dr. Vasey and NYJSM.com

February 8, 2009

Matthew Vasey, MD





© Caitlin Mitchell Photography


"I would like to encourage everyone to get involved with St. Jude Children's Research Hospital and check out some of the amazing work they have done. Dr. Vasey and NYJSM, could you explain to your readers a little bit about chemotherapy and the fight against leukemia in children?"




Thank you very much Melissa. We are delighted to look into this topic on your behalf with the hopes of generating some awareness and publicity for all the great work being done related to leukemia in children and in particular, some recent work done at St. Jude Children's Research Hospital.

Chemotherapy by definition is the treatment of disease by means of chemicals that have a specific toxic effect upon the disease-producing microorganisms or that selectively destroy cancerous tissue. (5) The chemotherapy that is now used to save and prolong life was once used to take and destroy life. The concept of chemotherapy today stems from the use of mustard gas first introduced as a weapon in the First World War. Mustard gas is a chemical that causes skin destruction, blindness, suffocation from your own fluid secretions into your airway and lung injury often leading to a slow and painful death. (7) While sporadic observations by doctors of the notable effects the chemical was having on the human lymphatic system and various blood cell lines the history of research related to mustard derivatives and other toxic gases were kept far out of the public eye as its contribution had been for the purposes of human destruction on a massive genocidal scale and other war-related purposes. Not until 1946 did doctors collaborate to publish a post World War II study looking the affects of poison gas on lymphomas, a cancer of lymph nodes. (3) This publication likely never would have taken place had an American war ship secretly carrying thousands of mustard bombs not been so publicly destroyed while stationed at Bari, Italy in what was referred to as the second Pearl Harbor. Similar observations soon after yet another tragic event made by military doctors in Bari on blood cells of the people exposed to the chemical. (4) Since this landmark publication in 1946 the world of chemotherapy and cancer related research as we know it today was begun.

Leukemia by definition is any of several cancers of the bone marrow that prevent the normal manufacturing of red and white blood cells and platelets, resulting in anemia, increased susceptibility to infection, and impaired blood clotting. (5) So what does that mean? Well, it is a testament to the complex make up of blood. The cells responsible for all of those things mentioned have to come from somewhere. They come from the bone marrow which fills the hollow areas of most bones. Imagine if you will a complex factory growing many different types of cells all destined to comprise the "blood" within vessels (vehicles on an interstate system) and lymph nodes (interstate truck stops and rest areas). Cancer is simply a pot-luck term for unregulated cell growth of any type, hopefully you can recall meiosis and mitosis from pretty much any high school science class where one cell becomes two, two cells become four and so forth.

What controls cells growth and replication? The answer is jeans, or genes that make proteins. These genes and proteins are hot topics in medical research and where I suspect most cancer research dollars are spent. In leukemia there is an imbalance of this cell growth in the bone marrow. You essentially have some "bully" cell line taking over, growing uncontrollably and spreading throughout the body like a wildfire. The problem is that these cells have a function in the body, both the over produced and under produced. If the blood cell types and amounts aren't what they are supposed to be in the body, you begin to have symptoms. The purpose of chemotherapy is to delicately and precisely kill the cells that are being over produced and restore a healthy balance for survival.

Acute leukemia as opposed to chronic for classification purposes are the most common forms of cancer in children with acute lymphoblastic leukemia (ALL) being five times more common than acute myeloid leukemia (AML). (9) Lymphoblastic and myeloid are just fancy names for cell lines like I mentioned before. Of course there are different types of cell lines within each of those. Yes, it gets quite complex and difficult to understand. Then you take into consideration lymphomas or cancers of lymph nodes (Recall: truck stops and rest area analogy) which are sometimes the result of dysfunctional gas pumps and cold pretzel machines or the progression of primary leukemia's meaning too many vehicles. Then of course the storm clouds can roll in as there are cancers from other organs ie. lung, breast, colon, liver etc ... that metastasize to lymph nodes!

Acute lymphoblastic leukemia occurs most often in children age 2-5 years old. (10) There are approximately 2500 to 3000 new cases in children each year. (6) Fortunately, since the 1980's, five year survival rates have reached almost 80%. (9) While there have been great improvements in the treatment of ALL, many children still die from this cancer. Thanks to facilities such as St. Jude's Children Research Hospital and others like it exciting breakthroughs continue to be made in this fight.

Children with ALL most commonly experience vague initial symptoms such as fever, bleeding, bone pain, swollen lymph nodes, headache or a few others that prompt visits to their doctors. A formal diagnosis and classification requires a bone marrow biopsy. Once a diagnosis is made the child should be transferred immediately to facilities specialized for children with cancer to begin treatment.

Treatment consists of various combinations of drugs separated into three phases usually lasting a few years to complete. The treatment is very dangerous as 2.6-5% of patients will die from the treatment itself. (2) Part one is "Induction Therapy" and it is 90% successful putting ALL in complete remission. (1) Part two is "Consolidation Therapy" which is an intensified regimen based on the child's predicted outcome (higher-risk vs. lower-risk) based on various factors with different drugs in order to prevent relapse. Lastly, part three is "Maintenance Therapy" which involves a less intense regimen completing the course of approximately 2 to 3 years. Those "cured" will continue to see their cancer doctor at least annually long after therapy has completed.

Despite the advances and recent successes in the management of children with ALL, there are still relapses where the leukemia comes back. This situation is very dangerous and relapsed ALL is the second most common cause of cancer-related death in children. This is where research plays such an important role. St. Jude's Cancer Research Hospital is a leader in this area of research. They are studying genes and proteins that might be able to predict which children will relapse from their initial therapy so they know to intensify a particular child's treatment with the hopes of preventing relapsed ALL. Just this month, St. Jude's Researchers is publishing their findings on this topic related to the IKZF1 gene that makes the IKAROS protein in medicine's most respected journal. (8)
Click here to read their abstract

Be sure to check out St. Jude Children's Research Hospital to find out how to get involved. http://www.stjude.org

REFERENCES:

1. Boissel, N, Auclerc, MF, Lheritier, V, et al. Should Adolescents With Acute Lymphoblastic Leukemia Be Treated as Old Children or Young Adults? Comparison of the French FRALLE-93 and LALA-94 Trials. J Clin Oncol 2003; 21:774.
2. Christensen, MS, Heyman, M, Mottonen, M, et al. Treatment-related death in childhood acute lymphoblastic leukaemia in the Nordic countries: 1992-2001. Br J Haematol 2005; 131:50.
3. Goodman LS, Wintrobe MM, Dameshek W, Goodman MJ, Gilman A, McLennan MD. Nitrogen mustard therapy. JAMA 1946. 132:126-32.
4. Hirsch, J. An anniversary for cancer chemotherapy. JAMA, 2006(296)12:1518-1520.
5. http://dictionary.reference.com
6. Jemal, A, Siegel, R, Ward, E, et al. Cancer statistics, 2008. CA Cancer J Clin 2008; 58:71.
7. Joensuu, H. Systemic chemotherapy for cancer: from weapon to treatment. Lancet Oncol 2008; 9:304.
8. Mullighan CG, Su X, Zhang J, et al. Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia. N Engl J Med 360:470, January 29, 2009.
9. SEER Cancer Statistic Review, 1973-1999. National Cancer Institute, Bethesda, MD, 2000. p.467.
10. Svendsen, AL, Feychting, M, Klaeboe, L, et al. Time trends in the incidence of acute lymphoblastic leukemia among children 1976-2002: a population-based Nordic study. J Pediatr 2007; 151:548.

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