About Authors:
Ms. Shilpa G. Lodha1, Vanita Nimje2, Ramzan Virani3
1 Department of Biotechnology,
Agnihotri College of Science, Ram Nagar,
Wardha 442001, India.
2 Department of Biotechnology,
Jankievi Bajaj college, Arvi Naka,
Wardha 442001, India.
3 Department of Biology,
Shivramji Moghe College of Science,
Panharkawada- 445 302, India.
Abstract
Many types of Cancer and Malingancy are known, in that Waldenstrom’s macroglobulinemia is rare cancer of an uncommon lymphoproliferative disorder characterized primarily by bone marrow infiltration and IgM monoclonal gammopathy. It should be considered a distinct clinicopathological entity rather than a clinical syndrome secondary to IgM secretion. The concentration of monoclonal IgM can vary widely in Waldenstrom’s macroglobulinemia and it is not possible to define a concentration that reliably distinguishes it from monoclonal gammopathy of undetermined significance (MGUS). Besides having lots of diagnosis method, there is no single accepted treatment for Waldenstrom’s macroglobulinemia. Commonly used treatment includes the monoclonal antibody rituximab, sometimes in combination with chemotherapeutic drugs such as chlorambucil, cyclophosphamide, or vincristine or with thalidomide. We have to find out the successful and low cost methods to cure Waldenstrom’s macroglobulinemia.
Reference ID: PHARMATUTOR-ART-1192
Introduction
There are many kinds of cancer which behave very differently. For example, bone cancer, lung cancer, breast cancer, etc. They grow at different rates and respond to different treatments. One such cancer isWaldenstrom’s macroglobulinemia (WM, also known as lymphoplasmacytic lymphoma) is cancer involving a subtype of white blood cells called lymphocytes. Waldenstrom’s macroglobulinemia (WM) is a type of lymphoproliferative disease, and shows clinical characteristics with the indolent non-Hodgkin lymphoma by production of high level of serum monoclonal immunoglobulin M [macroglobulin], elevated serum viscosity, and presence of lymphoplasmacytic infiltrate in bone marrow. Waldenstrom’s macroglobulinemia is a cancer of the B lymphocyte. This condition is considered to be “Lymphoplasmacytic Lymphoma” as defined by Revised European American Lymphoma classification (REAL) and World Health Organization (WHO) classification. It was first time discovered by Swedish physician Jan G. Waldenstrom in 1944 in two patients with bleeding nose and mouth, swollen lymph nodes, neoplastic plasma cells in bone marrow and increased velocity of blood. Waldenstrom’s macroglobulinemia is very much similar with multiple myeloma type of cancer with some differences like Organomegaly is common in Waldenstrom’s macroglobulinemia while it is absent in Multiple myeloma while renal disease are common in Multiple myeloma but absent in Waldenstrom’s macroglobulinemia. The cells of Waldenstrom’s macroglobulinemia have features of both plasma cells and lymphocytes are called lymphoplasmacytoid.
The Waldenstrom’s macroglobulinemia is caused by uncontrolled clonal proliferation of terminally differentiated B lymphocytes. The understanding of etiology is not yet known but a number of risk factors have been identified. A riskfactoris anything that affects your chance of getting a disease such as cancer. Researchers have found a few risk factors that make a person more likely to develop Waldenstrom’s macroglobulinemia, but most people with these risk factors never develop the disease. Even if a patient with Waldenstrom’s macroglobulenemia does have one or more risk factors, it is impossible to know for sure how much that risk factor contributed to causing the Waldenstrom’s macroglobulenemia.
Incidences:
The incidence has been estimated to be 0.3 per 100,000 white men and 0.17 per 100,000 white women, with approximately 1400 new cases occurring in the United States each year. In the UK the median age at presentation is 71 years and the median overall survival is 60months (Owen et al, 2001). No causative or predisposing factors are known, nor have any discrete susceptibility genes been discovered.
The Common Symptoms of Waldenstroms Macroglobulenia:
Following are the symptoms of Waldenstrom’s macroglobulenemia:
• Weakness, Loss of appetite, Fever, Enlarged lymph nodes, Swollen abdomen, Neurological problems [e.g. vertigo headaches, diziness] , Abnormal bleeding, Blurry vision, Bluish skin discoloration, Rash, Kidney problems, Heart problems, Raynaud phenomenon, Cold agglutinin disease, Cryoglobulinemia, fingers that change color upon pressure, etc.
The other major problems associated with Waldenstrom’s macroglobulenemia are Lymphadenopathy or Hepatomegaly, Hyper viscosity syndrome, Splenomegaly. Tracytopenis is found in approximately 50% with bleeding diathesis. It is very difficult to prevent this disease. Most people with Waldenstrom’s macroglobulinemia have no known risk factors. The risk factors that are known, such as aging, cannot be changed or controlled by a person. For these reasons, there is no known way to prevent this disease.
Mortaliy:
Waldenstrom’s macroglobulinemia is a chronic indolent lymphoproliferative disorder. Median survival time is approximately 78 months. Kaplan-Meier survival curves of patients with Waldenstrom’s macroglobulinemia do not show a plateau.
• The most important causes of death are progression of the proliferative process, infection, cardiac failure, and other causes, including renal failure, strokes, and GI bleeding.
• Transformation to a more aggressive immunoblastic variant is less common (6% of cases).
Causes:
The cause of WM is unknown. The potential role of viral agents such as the hepatitis C and human herpesvirus-8 remains controversial. A possible role for genetic factors has been suggested by reports of familial clustering of Waldenstrom’s macroglobulinemia. In a recent study, approximately 20% of 181 serial Waldenstrom’s macroglobulinemia patients presenting to a tertiary referral had a first degree relative with either Waldenstrom macroglobulinemia or another B cell lymphoproliferative disease. Reports of familial cases suggest a genetic predisposition.
Diagnosis:
Following test may be used to diagnose Waldenstrom’s macroglobulinemia.
• Blood Tests- Simple blood tests, such as CBC-D (complete blood count with differential count) and examination of the blood smears, can give clues to the diagnosis of Waldenstrom’s macroglobulinemia. There is also an increase in IgM that can be detected by protein electrophoresis.
• Computed Tomography (CT or CAT) Scan- A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities, tumors, enlarged lymph nodes, or a swollen spleen. Sometimes, a contrast medium (a special dye) is injected into a patient’s vein to provide better detail.
• Bone Marrow Aspiration and Biopsy- Lymphoma often spreads to the bone marrow, the spongy material in the center of bones where blood cells are produced. A sampling of the bone marrow can be important in the diagnosis of Waldenstrom’s macroglobulinemia, and it can help determine if the cancer has spread. In a bone marrow biopsy, a doctor takes a sample of marrow, usually from the back of the patient’s hipbone with a needle after the area has been numbed. A small amount of bone marrow is removed and examined under a microscope.
• Positron Emission Tomography (PET) Scan- A PET scan is a way to create pictures of organs and tissues inside the body. A small amount of a radioactive substance is injected into a patient’s body. This substance is absorbed mainly by organs and tissues that use the most energy. Because cancer tends to use energy actively, it absorbs more of the radioactive substance. A scanner then detects this substance to produce images of the inside of the body.
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Treatment:
Treatments for WM patients are aimed at relieving symptoms of marrow infiltration and hyperviscosity syndrome. Long term survival is possible for WM patients, although the disease is not curable. There is no single best treatment for all WM patients. Decisions regarding treatment need to be made in the context of the patient’s age, the nature and extent of symptoms, need for rapid disease control, candidacy for stem cell transplantation and quality of life. Some are described here under.
1. Alkylating Agents:
Chlorambucil with or without prednisolone is frequently used as the initial therapy in Waldenstrom’s macroglobulinemia. Responses are usually slow and toxicity is minimal providing the dose is adjusted if cytopenias ensue. The response rate is approximately 60%, depending on the criteria used, and the median survival approximately 60 months (Facon et al 1993, Demopoulos et al 1994a, Garcia-Sanz et al 2001). A recent study showed no difference in response rate or survival when chlorambucil was administered either daily or intermittently for 1 week every 6 weeks (Kyle et al 2000). The optimal duration of treatment is unknown. There are no data on the use of high-dose chlorambucil in WM. Cyclophosphamide alone or in combination is also effective.
2. Plasmapheresis :
Plasmapheresis is used to reduce the thickness of the blood. During this procedure, blood is taken from a vein and plasma is removed from the body after it is separated from the red and white blood cells. The blood cells are then mixed with a plasma substitute, usually an albumin solution, and returned to the patient. This procedure is often done continuously using a blood cell separator. Plasmapheresis is usually helpful in relieving the symptoms of hyper viscosity in people with Waldenstrom’s macroglobulinemia.
3. Targeted Therapy:
Targeted therapy is a treatment that targets specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. Monoclonal antibodies are a type of targeted therapy. The monoclonal antibody rituximab (Rituxan) is used to treat many different types of B-cell lymphoma. Rituximab works by targeting a cell-surface molecule called CD20. When the antibody attaches to this antigen, some lymphoma cells die and others appear to become more susceptible to chemotherapy. Rituximab can be used either alone or in combination with chemotherapy in people with Waldenstrom’s macroglobulinemia.
4. High Dose Chemotherapy With Autologous Stem Cell Transplantation:
Blood-forming stem cells are harvested and stored, then given back to the patient following high-dose chemotherapy. The harvested cells may be treated before transplantation to get rid of cancer cells. The transplanted cells travel to the bone marrow and begin to produce new blood cells.
Current Research:
Research for Waldenstrom’s macroglobulinemia is ongoing. The following advances may still be under investigation in clinical trials and may not be approved or available at this time.
New Treatments: These therapies are being explored in clinical trials:
• Sildenafil (Viagra) blocks the function of several proteins necessary to the survival of certain types of cancer, and laboratory tests have shown that it can destroy Waldenstrom’s macroglobulinemia cells.
• PR-171 is an experimental drug that is a proteasome inhibitor, an enzyme responsible for degrading a wide variety of cellular proteins.
• AVN944 is an enzyme inhibitor that is being tested in patients with advanced Waldenstrom’s macroglobulinemia.
Drug Combinations: Drugs are being used in combination to treat Waldenstrom’s macroglobulinemia:
• Monoclonal antibodies, such as rituximab can locate cancer cells and eliminate them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Adding rituximab to combination chemotherapy may eliminate more cancer cells.
• The drug fludarabine combined with cyclophosphamide is sometimes used to treat patients with advanced and/or symptomatic Waldenstrom’s macroglobulinemia, as is another combination of drugs called DTPACE (dexamethasone [Decadron], thalidomide [Thalomid], cisplatin [Platinol], doxorubicin [Adriamycin], cyclophosphamide, and etoposide [VePesid]) plus rituximab.
Conclusion:
The concentration of monoclonal IgM can vary widely in Waldenstrom’s macroglobulinemia and it is not possible to define a concentration that reliably distinguishes it from monoclonal gammopathy of undetermined significance (MGUS). Currently, there is no any successful treatment for Waldenstrom’s macroglobulinemia. Hence researcher has to find out the new ways to treat this disease.
References:
[1] Ghobrial IM, Witzig TE, Waldenstrom Macroglobulinemia. Current Treatment Options in Oncology, June 2004, Vol. 5, No. 3: 239-47.
[2] Treon SP, Hatjiharissi E, Leleu X, Roccaro A, Merlini G. Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma. In: Hoffman R, Benz EJ, Shattil SS, et al, eds. Hematology: Basic Principles and Practice. 5th ed. Philadelphia, Pa: Elsevier Churchill Livingstone; 2008:chap 88.
[3] Owen RG, Treon SP, Al-Katib A, et al. Clinicopathological definition of Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia. Semin Oncology 2003;30:110–115. [PubMed]
[4] Jaffe ES, Harris NL, Stein H, Vardiman JW. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001. 12.
[5] Massari R, Fine JM, Metais R. Waldenstrom's macroglobulinaemia observed in two brothers. Nature. 1962;196:176–178. [PubMed]]
[6] Chang WJ, Schop RF, Price-Troska T, et al. Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma. Blood. 2006;108:2755–2763. [PMC free article] [PubMed]
[7] Steve Krisch’s story, “Waldenstrom’s macroglobulinemia: My story.”
[8] Meredith A. Lazar, MD; Brett R. Levine, MD, MS; German Steiner, MD; William L. Jaffe, MD et al. Bilateral THA in a patient With Waldenstrom’s Macroglobulinemia.
[9] Gertz MA, M.D. Waldenstrom Macroglobulinemia: A Review of Therapy. 2004 Mayo Foundation for Medical Education and Research. Yang L, Wen B, Li H, Yang M, Jin Y, Yang S, Tao J (1999). Autologous peripheral stem cell.
[10] Nicholos GL, Savage DG (2004). Timing of rituximab/fludarabine in Waldenstrom’s Macroglobulinemia may avert hyperviscosity.
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