Multiple myeloma (MM), a neoplasm of plasma cells, approximately 1Â to 5 per 100 000 individuals each year worldwide were affected with a higherÂ incidence in the West (a). It is the major hematologic malignancy in the United State and about 10790 deaths is estimated due to myeloma in 2007 (b). Multiple myeloma is a cancer in which the the abnormal plasma cells are found in the bone marrow. Normally , plasma cells are in charge in producing the immune globulins, the immune protein that our body needs to fight infections. However , in myeloma , the abnormal plasma cells produced uncontrollably causing the distruptions of normal bone marrow function , destruction of the surrounding bone, and production of excessive amounts of monoclonal protein called M-protein. Therefore, what could be the best solution to restore the production of the normal immunoglobulins that help fight infections?
Figure 1 Figure 2
Figure 1 : Normal plasma cells help protect the body from germs and other harmful substances.
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Figure 2 : Myeloma cell (abnormal plasma cell) making M proteins.
http://www.cancer.gov/cancertopics/wyntk/myeloma/page2#a1 (180 words)
1. CONVENTIONAL CHEMOTHERAPY
Chemotherapy is one of the common treatment that is use to treat cancers. Chemotherapy acts by killing the cancerous cells which grow and divide rapidly and keeping them from growing, dividing and spreading. However , it can also harm the healthy cells that divide quickly such as those that line the mouth and intestines.
Thalidomide (ThalidomidÂ®), lenalidomide (RevlimidÂ®), and bortezomib (VelcadeÂ®) has been shown to be highly effective in diagnosed and relapsed MM patients whether to used it alone or combine with the other chemotherapy drugs (j). For example, patients taking bortezomib plus PLD were more likely to survive than patients taking bortezomib alone.These combinations often produce more effective results than the older agents as can be seen in Graph 1.
"Such combinations produce more effective anti-myeloma activity with less added toxicity,"
Dr. Raymond Alexanian
M.D. in the Department of Lymphoma and Myeloma
University of Texas M.Â D. Anderson Cancer Center.
( 336 words )
Graph 1 : The overall survival of patients taking bortezomib (Velcade) or bortezomib plus pegylated liposomal doxorubicin (PLD, Doxil) for treatment of multiple myeloma.
( 361 words )
2. HIGH DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL THERAPY(ASCT)
Autologous stem cell transplant is a procedure that use one's own stem cell in conjunction with high-dose chemotherapy, which is frequently more effective than conventional chemotherapy in destroying myeloma cells. Since high-dose chemotherapy also destroys the normal blood-producing stem cells in the bone marrow, these cells must be replaced in order to restore blood cell production (q).
The first step in the ASCT is the collection of stem cells from the patients themselves which can be harvested from the peripheral blood, drugs are used to "mobilize" them.Â A medication called a Granulocyte-Colony Stimulating Factor (G-CSF) (e.g. NeupogenÂ®) is used to stimulate the bone marrow to increase the number of stem cells in the blood (p).Â Pheresis is the process that is used to collect the stem cells from the blood. Â They are then frozen and stored until needed. After high-dose chemotherapy is completed, the stored stem cells are thawed and infused back into the patient.Â In time, the transplanted stem cells begin to produce new healthy blood cells in order to replace the normal cells which is lost during high-dose chemotherapy.
Figure 3 : The infused stem cells travel through the bloodstream and settle in the bone marrow, where they begin to produce new white blood cells, red blood cells, and platelets.
http://www.themmrf.org (583 words)
Â ASCT have shown some progressive improvement in the overall survival from the time of relapse was observed during the past decade (l). This can be seen in Graph 2 below. Part A shows the overall survival of from the time of post transplantation relapse whilst in part B illustrates the overall survival from the time of post transplantation relapse grouped and whether they were treated subsequently with one or more of the newer drugs (thalidomide, bortezomib, or lenalidomide).
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Graph 2 : The overall survival from time of relapse after ASCT.Â
Many people diagnosed with cancer wonder if they should quit their job and should tell their employer or not. They may be worried that they will be treated differently. This will affects one's emotions but the advantage to letting the boss know is that it will be easier to rearrange work schedule due to treatment.
Another concern about working is the potential exposure to infections from co-workers when their white blood cells counts are low because of chemotherapy.They will be more susceptible to infections and need to take more precautions that is urge co-workers who are ill to stay away from work area and try to minimize contact with public when the white counts are low.
As long as one can do their work there are laws to protect them from discrimination due to cancer diagnosis such as The Americans with Disabilities Act (ADA) and Family and Medical Leave Act (FMLA) (u,v). This law protects workers against discrimination and protects individuals who need to take time off from work due to their own illness or to care for a loved one.
Chemotherapy drugs are very expensive which depends on many factors which include type of drugs used, the amount of the dose, the duration and the place of the treatment (hospital or clinic)(k).
In Malaysia the cost of chemotherapy using the latest chemotherapy drugs will cost RM10,000 to 30,000 per cycle (x). Â Whilst in the UK, thalidomideÂ which is more cost-effective than bortezomib will costs around £3,000 per cycle (m). These expenses only include drug cost which exclude many other expanses like the insurance. If the drugs taken is the combination of other drugs, the cost of chemotherapy treatment may increase.
Many patients who are suffering from cancer cannot afford such high cost of treatment.As a result ,they treatment will be delayed and some of them even skip it entirely just because of the cost of chemotherapy.Thus ,many may suffer earlier death or disability (k).
BENEFITS AND RISKS
1 ) Chemotherapy
The aim for chemotherapy is to control the disease as we know that multiple myeloma is an incurable disease. Chemotherapy increase the chances in prolong the life of the patient by significantly reduces the chances of cancer relapse and death from the disease.Apart from slows down the progression of multiple myeloma , chemotherapy also can eliminate the amount of the abnormal plasma cells that canÂ travelÂ and spread to other parts of the body. As a result , the chances of secondary cancer occuring will be reduced (n).
Patients undergone chemotherapy will be more vulnerable to infections as their blood counts are low due to the effects of the drugs in chemotherapy in which it destroy the fast-growing cells like white blood cell.Thus , their immune system are weakened (s). The side-effects of chemotherapy may also develop into more severe nerve damage (naturopathy) which may cause impaired walking abilities, severe bladder dysfunction, and disabling sensory loss. Futhermore , a second cancer also may be develop (r).
2 ) High Dose Chemotherapy with Autologous Stem-cell therapy
Since the stem cell was taken from the patient itself , therefore there will be no risk of rejection .
The most significant potential side effects of stem cell transplantation would be due to the high-dose chemotherapy. The short-term side effects include nausea, vomiting, diarrhea, mouth sores , skin rash, and hair loss (t). ASCT patient will be susceptible to infection, anemia, and bleeding caused by low blood cell counts as a result of the high-dose chemotherapy which destroys blood-producing cells in the bone marrow. However, the severity of the side effects can be reduced byÂ palifermin that help to reduce the duration and severity of the mouth sores.
1)Autologous Immune Enhancement Therapy (AIET)
In AIET, the NK cellsÂ and T lymphocytes are isolated from the peripheral blood of the cancer patients which is during the remission in patients who undergo chemotherapy.The cells are expanded to 25 - 30 fold until they are activated .Then they are reinfused back into the patient's body. These cells act against the cancer cells effectively. The activated NK cell will 'clings' to the membrane of the cancer cell and injects toxic granules which dissolve the target cell when they encountering a tumour cell. The cancer cell dies in less than five minutes and the will moves on to its next target cancer cell.
2) Dendritic cell based immunotherapy
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The dendritic cell is a type of antigen presenting cell (APC) that help to activate aÂ cytotoxicÂ response towards anÂ antigen (y). In this treatment , the dendritic cells are harvested from a patient. Later, these cells are pulsed with an antigen or transfected with aÂ viral vector in order to activate the cells. The activated dendritic cells are then infused back into the patient and will present the antigens to effector lymphocytes (CD4+ T cells, CD8+ T cells, and in specialized dendritic cells, B cells also). This will induces a cytotoxic response to occur and reacts against these antigens and anything that may present these antigens. In MM patients, the Tumor Antigens are presented to dendritic cells that will cause the immune system to target on these antigens and destroy all the tumor cell.
3) T cell based adoptive immunotherapy
Adoptive cell transfer uses T cell-based cytotoxic responses to attack cancer cells. The T cell was taken from the patient's own white blood cells which being isolated in the laboratory. This process technically called as the autologous lymphocytes (z) .Chemotherapy drugs like the cyclophosphamide and the fludarabine are given to deplete the patient's remaining lymphocytes. Meanwhile, the aggressive tumor-killing lymphocytes are identified , let them multiplied in the lab before being re-injected back into the patient. Finally , the patient will receive a high dose of interleukin-2 (a protein made by the body) which induces the tumor-fighting cells mature and multiply. The ACT method basically can be use to treat MM patient by using their own immune system to specifically attack an the cancerous cells.
EVALUATION OF SOURCES
"Alkylating agents act much like radiation and often refered to as a radionemics.They cause cancer cells to die by attaching to their DNA molecules at several sites resulting in DNA breaking.This means that alkylating agents would also cause considerable damage to the patient normal cell possibly leads to secondary cancer after a variable latent period. "
This extract was taken from the book called the (c) " The Natural Strategies For Cancer Patient" by Russell L. Blaylock , M.D in 2003. This book can be trusted because Dr Russell is the board certified neurosurgeon , an author and a lecturer .He has practiced neurosurgery for the past 25 years before devoted himself to the nutritional studies and research.Eventhough the book was published in 2003 and may be the information is back-dated but the extract agrees with many other sources like (h)http://www.medicinenet.com/script/main/art.asp?articlekey=21716 with the following extract:
"Chemotherapy can cause permanent changes or damage to the heart, lungs, nerves, kidneys, reproductive or other organs. And certain types of chemotherapy may have delayed effects, such as a second cancer, that show up many years late. "
"Â A group of new therapies has been developed and approved for use in MM patients, including thalidomide (ThalidomidÂ®), lenalidomide (RevlimidÂ®), and bortezomib (VelcadeÂ®). Used alone or paired with traditional chemotherapy, these drugs have been shown to be highly effective in recently diagnosed and relapsed MM patients. "
This extract is taken from reference (i) http://www.medicalnewstoday.com . This source is very reliable and factual because this article referred to the study from German Cancer Research Center which I believe is trustable and valid as it Â is the largest biomedical research institute in GermanyÂ and more than 1000 scientists are working in developing novel approaches in the prevention, diagnosis, and treatment of cancer. Besides this extract agrees with many other sources ,(l) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2254544/?report=abstract with the following extracts "Patients treated with one or more of the newer drugs (thalidomide, lenalidomide, bortezomib) had longer survival from relapse".