Multiple Myeloma and Waldenstrom’s Macroglobulinemia

In these two disorders, the cancerous or neoplastic cells produce abnormal proteins known as monoclonal antibodies. Normal antibodies are specific proteins produced by certain white blood cells (lymphocytes and their close relative, the plasma cell) that help fight infections. Normal people have many different groups (or clones) of lymphocytes and plasma cells that make a large variety of antibodies without any predominant type. A person afflicted with multiple myeloma or Waldenstrom’s macroglobulinemia has unregulated growth of a single clone of cells that often produces a large amount of a single useless antibody with suppression of normal antibody production.

Multiple Myeloma Treatment
Multiple myeloma is a cancer of plasma cells usually associated with abnormal antibody production, anemia, fatigue, bone pain and kidney insufficiency. Waldenstrom’s macroglobulinemia behaves like a low-grade lymphoma but with the production of large amounts of a specific type of antibody (IgM) that may cause the blood to become very thick, leading to symptoms such as severe fatigue, coma and bleeding problems. In both disorders, patients have increased susceptibility to infection.

Multiple myeloma affects almost 15,000 new patients a year. The neoplastic plasma cells grow in the bone marrow without normal regulation. In addition to producing monoclonal antibodies, these cells also produce chemicals known as cytokines that cause bone destruction. The destruction of bone may release large amounts of calcium into the blood stream causing excessive urination (and resulting dehydration), severe malaise, lethargy and even coma. Patients may feel tired because of impairment of red blood cell growth, resulting in anemia. Large amounts of antibody protein may cause fatigue and kidney damage.

Various tests are performed to diagnose and stage multiple myeloma. Blood tests help assess the degree of anemia, the amount of the abnormal protein, status of the kidneys and blood calcium level. A bone marrow biopsy and aspirate helps assess the degree of marrow replacement by the abnormal population of cells. A skeletal survey, X-rays of all the major bones of the body, is performed to look for lytic lesions (holes in the bones) and fractures.

Various modalities are used in the treatment, such as conventional dose chemotherapy, high-dose chemotherapy with stem cell rescue transplants, immunomodulators such as thalidomide, radiation therapy and orthopedic intervention when needed. Novel agents that interfere with normal cell control mechanisms, such as bortezomib (Velcade) are being used here to give patients every possible chance to combat the disease.

Newly diagnosed patients may be treated with standard chemotherapy regimens (such as combination of vincristine, doxorubicin and dexamethasone), or may be eligible for trials of new treatment regimens. For patients with relapsed or refractory disease, Rush offers traditional and investigational protocols with agents such as Doxil, bortezomib, arsenic trioxide and Revemid, a thalidomide-like compound, but much more potent than the parent compound.

Waldenstrom’s Macroglobulinemia Treatment
Waldenstrom’s Macroglobulinemia is a rare, low-grade-lymphoma-type disease accompanied by production of a large amount of a specific type of monoclonal protein, namely an IgM protein. The cancerous cells are plasmacytoid lymphocytes. Patients with Waldenstrom’s macroglobulinemia often develop enlarged organs (liver, spleen or lymph nodes) because neoplastic cells invade these areas. Fatigue and weakness are common symptoms. Patients may develop a hyperviscosity syndrome (thickened blood) due to the large amounts of abnormal protein in the blood. Patients with this syndrome may experience severe lethargy, bleeding, headaches, vision problems, numbness and tingling in hands and feet. The reason that the IgM monoclonal protein behaves differently from the monoclonal protein found in multiple myeloma (IgG or A or D) is that individual molecules of IgM have a tendency to link together, with five IgM molecules clustering to form a super-sized protein.

Blood tests are performed to diagnose and evaluate Waldenstrom’s macroglobulinemia. A bone marrow biopsy and aspirate is performed to assess the degree of marrow infiltration by the cancer cells. In addition, measurement serum viscosity documents the degree of blood thickness. Patients with symptoms of hyperviscosity may need plasmapheresis. This procedure removes the abnormal protein from bloodstream by removing the patient’s plasma, where the abnormal proteins reside. Definitive therapy is with chemotherapy or a combination of chemotherapy and immunotherapy.