Mantle Cell Lymphoma
Mantle Cell Lymphoma
Description, Causes and Risk Factors:
Lymphoma is a cancer of the white blood cells, namely lymphocytes. Lymphoma is the most common blood cancer and the third most common cancer of childhood. Lymphoma occurs when lymphocytes, a type of white blood cell, grow abnormally. The body has two types of lymphocytes: B lymphocytes, or B-cells, and T lymphocytes, or T-cells. Although both cell types can develop into lymphomas, B-cell lymphomas are more common. Like normal lymphocytes, those that turn malignant can grow in many parts of the body, including the lymph nodes, spleen, bone marrow, blood or other organs.
MCL is a B-cell lymphoma that gets its name because mantle cell tumors are composed of cells that come from the “mantle” zone of the lymph node. Frequently, MCL is diagnosed as a stage 4 disease, often present in lymph nodes above and below the diaphragm and in most cases involves the gastrointestinal tract and bone marrow. MCL is a relatively rare disease, constituting only about 6 percent of all NHL (non-Hodgkin lymphoma) cases in the United States (i.e., only about 3,000 cases per year in the U.S.). This lymphoma usually affects men over the age of 60.
Generally, the cancer is not confined to one place in the body — that is, it's not localized. MCL occurs in one or more lymph nodes, but at the same time it can also appear in the digestive system, lungs, skin, spleen, bone marrow, or blood. Often, MCL has spread by the time it is diagnosed by a doctor.
Researchers discovered that most people with MCL have a mutation in two of their chromosomes, the strands of genes that shape all of our characteristics. In MCL , parts of chromosomes 11 and 14 exchange places, what doctors call a translocation. This translocation leads to the release of too much of a substance called cyclin D1. A buildup of cyclin D1 leads to the uncontrollable growth of a type of B cell and MCL. An excess of cyclin D1 is almost always found in the lymph nodes of people with MCL.
Another important research finding was that MCL could be identified through either the presence or absence of B-cell markers on the surface of MCL cells. There are several types of markers associated with MCL: CD5, CD19, and CD20. The absence of other B-cell markers, such as CD23 and CD10, is also used to identify MCL.
Stage II: Two or more lymph node regions are affected, but the affected regions are restricted to either above the diaphragm or below the diaphragm.
Stage III: The affected areas are found on both sides of the diaphragm.
Stage IV: The affected areas are on both sides of the diaphragm, and the cancer has spread to other organs, such as the liver or bone marrow.
Stage I: Only one lymph node region or area of the body is affected.
Painless swelling in the:
High fever with no identifiable cause.
Excessive night sweats.
At the time of diagnosis most patients have disease involving multiple lymph nodes and other sitesof the body. These sites may include the spleen, marrow and blood, the lymph nodes in the throat(tonsils and adenoids), the liver, or the gastrointestinal tract. In the gastrointestinal tract acondition known as “multiple small intestine polyps” may result from the lymphoma cell growth.MCL cells may invade the brain and spinal cord.
In order to diagnose the presence of MCL, a biopsy is usually done first.A biopsy is a minor diagnostic surgery in which a small amount of tissueis removed for observation.To confirm the diagnosis of MCL, doctors will first view abiopsy sample under the microscope, often complimentingthis step with sensitive molecular tests that detect alterationsin the genetic material of tumor cells in the biopsy tissue.Overproduction of a growth-promoting protein called cyclinD1 is found in more than 90% of casesand is considered a very sensitive tool for diagnosing MCL.The overproduction of cyclin D1 is caused by a molecularevent called a genetic translocation, in which inappropriateshuffling of DNA directs cells to make large quantities ofthis growth-stimulating protein.
CT scan and PET scan: It may be recommended that you get a CTscan (a type of x-ray) to check for tumors in areas ofyour body that are susceptible to MCL, including thelymph nodes, spleen, and liver. These are likely areasfor MCL to spread.
Colonoscopy: Your doctor may recommend aprocedure called a colonoscopy. A thin, flexible,hollow lighted tube is used to look inside the entirecolon.
Endoscopy: MCL can spread to the esophagus andstomach. The endoscopy procedure uses a fiber opticcamera to examine these areas.
Blood tests: These tests check the levels ofcalcium, uric acid, and certain proteins called LDHand beta 2-microglobulin. They also determinethe concentration of red and white blood cells andplatelets.
After the stage of your MCL has been determined, your doctor can suggest proper treatment. Other than chemotherapy and radiation therapy, there are no standard forms of treatment for MCL, however there are several treatment options available for MCL patients:
MCL is an aggressive form of NHL (non-Hodgkin lymphoma) that requires combination chemotherapy. Like other forms of NHL, there is no consensus on the frontline or subsequent line treatments. Up-front treatments can range from simple R-CHOP to complex regimens like hyperCVAD, EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) and even stem cell transplant. MCL is considered a difficult cancer to treat. However, it is important to remember that survival times for individual patients can vary quite dramatically, since statistical figures can only describe the general features of a population. Recent research has unveiled novel combinations of chemotherapy, new biological therapies and combination regimens that show promise in treating MCL, and possibly, in improving survival from this lymphoma. In fact, in recent years, major advances are being made routinely to improve the treatment of MCL.
Although there is no clear consensus about the best treatment for individual MCL patients, a common chemotherapeutic treatment approach that has been used is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Recent studies suggest that combining chemotherapy regimens with the monoclonal antibody rituximab (Rituxan) improves patients' response rates and possibly overall survival. More intensive chemotherapy regimens are also being tried. One example is hyperCVAD-R (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine and rituximab). Supplementing hyperCVAD with rituximab or stem cell transplantation has shown promising early results and although more intensive, may be better than R-CHOP for selected younger patients with the disease. HyperCVAD is usually administered as an inpatient in the hospital. Other combinations of drugs like a dose intense R-CHOP plus ICE chemotherapy (iphosphamide, carboplatin and etoposide) may be equally as active as hyperCVAD and don't require long hospitalizations.
Immunotherapy: Several clinical studies are investigating the effectiveness of immunotherapy, in which the power of the immune system is enlisted to fight cancer. Monoclonal antibodies, such as Rituxan, work by targeting and attaching to surface markers on lymphoma cells and gluing themselves on. This action triggers the patient's immune system to kill the cancer cells as it might attack any foreign invader, such as a bacterium or virus. Radioimmunotherapy is a modification of this approach, in which a monoclonal antibody is combined with a radioisotope particle, “arming” the antibody with a local source of radiation. After a monoclonal antibody hones in on its cancer cell target, radiation destroys it and nearby cancer cells in what is called a “crossfire effect.” Two such antibody drugs, Iodine-l3l tositumomab (Bexxar) and Yttrium-90 ibritumomab tiuxetan (Zevalin) have been approved to treat some types of NHL and are currently being tested against MCL. In one study, Bexxar is being tested in a sequential treatment with CHOP.
Side effects may include: Anemia, fatigue, nausea, vomiting, hair loss, risk of infection, diarrhea, easy bruising, mouth sores, loss of appetite, peripheral neuropathy, flu-like symptoms.
Hematopoietic Stem Cell (bone marrow) Transplantation: Bone marrow, the spongy material found inside bones, contains immature “stem” cells. These cells develop into three types of cells found in the blood: red blood cells that deliver oxygen to all parts of the body and take away the waste product carbon dioxide; white blood cells that protect the body from infection; and platelets that help blood clot. If very high doses of chemotherapy or radiation are used to destroy cancer cells, normal bone marrow is destroyed. A stem cell transplant can help restore healthy bone marrow. There are two sources of hematopoietic stem cells: allogeneic sources, in which patients receive bone marrow or stem cells donated by another person, and autologous sources, in which patients receive their own cells. Autologous stem cell transplantation (SCT) is far more commonly used than is allogeneic stem cell transplantation (SCT). High-dose chemotherapy coupled with SCT can be used for MCL patients who have failed their initial chemotherapy but are responsive to a second chemotherapy regimen, although some researchers feel that allogeneic SCT is better for patients who have had a relapse and that autologous SCT should only be used to treat patients as part of initial therapy. Mini-stem cell transplants are procedures in which hematopoietic stem cells are received from an allogeneic donor, but the chemotherapy administered is “minidose.” These procedures are quite new and are therefore still considered investigational. Unlike a normal hematopoietic stem cell transplant in which high dose chemotherapy is administered, in these procedures the patient receives low or normal dose chemotherapy, just enough to allow the body to accept the donor cells. This approach is used to take advantage of the graft-versus lymphoma effect, in which the transplanted cells recognize the tumor as a foreign invader and activate immune cells to destroy it. Patients who experience a graft-versus lymphoma effect may remain in remission for a longer period. Also, because patients receive lower doses of chemotherapy, they may avoid some of the toxicities seen with higher dose chemotherapy.
Side effects may include: Anemia, fatigue, high risk of infection, easy bruising, nausea, vomiting, hair loss, mouth sores.
Presently, there are many exciting new drugs that appear to have promising activity in MCL. Many of these therapies are based upon what scientists have learned about the biology of human cells. For example, a new medication, called Velcade (bortezomib or PS-341), acts to disrupt a cellular process called the ubiquitin-proteasome pathway, which performs a critical role in eliminating proteins in normal and cancer cells. Velcade has been approved by the FDA for the treatment of patients with MCL who have relapsed or refractory disease after at least one prior therapy. The approval is based on a clinical trial involving 155 patients with relapsed MCL. Velcade was also approved by the FDA in treatment of multiple myeloma, another blood cancer.
Other drugs are also being investigated that show promise in treating this challenging disease. Scientists know that a protein called bcl-2 protects cancer cells from dying. They are testing new drugs that intentionally block bcl-2. One of these experimental drugs is called oblimersen (Genasense). This drug leads to the degradation of Bcl-2 messages in cancer cells, increasing their sensitivity to chemotherapy.
Another novel class of drugs that have recently emerged as having promising activity in MCL include the mTOR inhibitors. mTOR stands for the `mammalian target of rapamycin'. Rapamycin is a naturally occurring compound that happens to inhibit mTOR quite effectively. mTOR plays an important role in turning on a host of proteins called transcription factors, which then can influence cell growth. Excessive activation of the mTOR pathway can lead to excessive cell growth, while inhibition of mTOR can lead to inhibition of cell growth and even cell death.
Clinical trials: Over 150 clinical studies are currently underway to test new treatments for MCL.
NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.
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