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Old 09-13-2015, 06:51 PM
gdpawel gdpawel is offline
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Default Surviving Stage IV Mantle Zone Lymphoma

Robert A. Nagourney, M.D.

Just a year ago a colleague referred a patient for consultation. This 80 year old gentleman, himself a physician, presented with extensive lymphadenopathy. Lymph node and bone marrow biopsies established mantle zone lymphoma with over 40% marrow infiltration. The PET/CT confirmed large volume retroperitoneal disease. As we discussed options, I explained that laboratory analysis might help us to select the most active treatments.

Mantle zone lymphoma is a subtype of non-Hodgkin's lymphoma constituting approximately 6% of all cases diagnosed in the U.S. It is associated with a specific genetic translocation known as the t(11;14) that upregulates the protein cyclin D1 causing rapid cell turnover. It is considered among the most aggressive of the B-cell neoplasms and the treatments, among them one known as hyper CVAD, can be very toxic. Hoping to avoid excessive toxicity we conducted our functional profile to explore treatment options. The results were highly gratifying. In addition to activity for Bortezomib, the patient had a very favorable profile for Bendamustine.

With our laboratory results in hand, I suggested the relatively mild combination of Rituxan plus Bendamustine. This combination which was found active in the patient's tissue culture had been reported by a German group to provide good results when compared with R-CHOP.

After three cycles of treatment, there was much improvement. After six cycles still more. The question then became: Should we change to an alternative treatment? After conferring with a consultant, I opted to complete eight total cycles and then moved to maintenance Rituxan. With three months additional follow up (off Bendamustine) the recent PET-CT is entirely normal. All parameters have normalized.

Soon to be 81, the patient continued to practice medicine and maintained an extremely active lifestyle throughout his entire therapy. He was able to receive a simple combination that provided durable benefit but very little toxicity. My initial concern that I might be undertreating him was put to rest by our laboratory analysis that gave me the confidence to use this comparatively mild combination. Even with a diagnosis as grave as Stage IV Mantle Zone Lymphoma, this patient was not too old to be cured.
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Old 09-13-2015, 06:58 PM
gdpawel gdpawel is offline
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Default Mantle Cell Lymphoma

Lymphoma is the most common blood cancer. The two main forms of lymphoma are Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). Lymphoma occurs when cells of the immune system called lymphocytes, a type of white blood cell, grow and multiply uncontrollably. Cancerous lymphocytes can travel to many parts of the body, including the lymph nodes, spleen, bone marrow, blood, or other organs, and form a mass called a tumor. The body has two main types of lymphocytes that can develop into lymphomas: B-lymphocytes (B-cells) and T-lymphocytes (T-cells).

Mantle cell lymphoma (MCL) is a rare, B-cell NHL that most often affects men over the age of 60. The disease may be aggressive (fast growing) but it can also behave in a more indolent (slow growing) fashion in some patients. MCL comprises about five percent of all NHLs. The disease is called "mantle cell lymphoma" because the tumor cells originally come from the "mantle zone" of the lymph node. MCL is usually diagnosed as a late-stage disease that has typically spread to the gastrointestinal tract and bone marrow.

A diagnosis of MCL requires taking a small sample of tumor tissue, called a biopsy, and looking at the cells under a microscope. A blood test may also be necessary to measure the white blood cell count and certain proteins, which help to diagnose MCL. Other tests, such as a bone marrow biopsy and a computed axial tomography (CAT) scan may be used to confirm a diagnosis and to determine what areas of the body are involved by the cancer.

Overproduction of a protein called Cyclin D1 is found in more than 90 percent of patients with MCL. Identification of excess Cyclin D1 from a biopsy is considered a very sensitive tool for diagnosing MCL. One-quarter to one-half of patients with MCL also have higher than normal levels of certain proteins that circulate in the blood, such as lactate dehydrogenase (LDH) and beta-2 microglobulin. Measuring these and other proteins can help doctors determine how aggressive an individual patient's MCL is and may guide therapy decisions.

The type of treatment selected for a patient with MCL depends on multiple factors, including the stage of disease, the age of the patient, and the patient's overall health. For the subset of patients who do not yet have symptoms and who have a relatively small amount of slow growing disease, "watchful waiting" and monitoring the disease for progression may be an acceptable option. MCL is usually diagnosed once it has spread throughout the body, and the majority of these patients will require treatment. Initial treatment approaches for aggressive MCL in younger patients include combination chemotherapy, typically in combination with the monoclonal antibody rituximab (Rituxan), as first-line treatment, followed by autologous stem cell transplant (in which patients receive their own stem cells). HyperCVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and cytarabine) plus rituximab are recommended as aggressive induction therapy and are associated with durable remissions in newly diagnosed patients For older patients, chemotherapy followed by a prolonged course of rituximab alone, known as maintenance, is often recommended. A common chemotherapeutic treatment approach used to treat MCL is called R-CHOP, which combines rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. Bendamustine (Treanda) in combination with rituximab is another common first-line treatment option. Several additional intensified chemotherapy combinations are also used in combination with rituximab, particularly in younger patients.

Although high-dose chemotherapy followed by allogeneic (in which patients receive stem cells from a donor) stem cell transplantation is very intensive and causes various side effects, it may increase response times for selected younger patients.

Bortezomib (Velcade) is approved by the U.S. Food and Drug Administration for the treatment of MCL patients who have received at least one prior therapy. In October 2014, bortezomib for injection was approved for previously untreated patients with MCL. Bortezomib is the first treatment in the United States to be approved for use in previously untreated patients with MCL; for more information, please visit: Bortezomib (Velcade)

On June 5, 2013, the U.S. Food and Drug Administration (FDA) approved lenalidomide (Revlimid) for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies.

Source: Lymphoma Research Foundation
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