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Stem-cell transplantation

Stem-cell transplantation is often used as consolidation therapy after a patient has achieved a complete remission (CR), or after a second CR is achieved in recurrent disease. It is also used in patients who are unable to achieve a remission with first line, or so called standard, therapy.

• Stem-cell transplantation is more effective than conventional chemotherapy in killing myeloma cells. However, it is a physically and emotionally demanding treatment, so not everyone with myeloma is a candidate for such an aggressive approach. Stem cell transplantation is most often used for younger patients or selected older patients with a good performance status. It has been associated with higher remission rates, as well as longer remission and survival than those of standard-dose chemotherapy.
• This procedure involves the use of very high doses of chemotherapy to kill the aggressive cancer cells.
• The chemotherapy dose is designed to destroy the marrow, in essence to keep the marrow from spontaneously recovering and producing abnormal cells once again.
• The individual is then given a transfusion of healthy bone marrow stem cells. The number of cells infused is calculated to be sufficient to induce marrow recovery with the bone marrow stem cell precursors. Conceptually, an allogenic (from a tissue-matched family donor) stem cell transplant would be preferable, in order to infuse tumor-free stem cells. However, because myeloma is a disease of the elderly, few patients may meet criteria for such an aggressive approach, and those who undergo standard allogeneic transplantation are at higher risk of complications and death.
• Should one's own stem cells be used, the reinfusion after high-dose therapy is referred to as autologous (one's own). Autologous re-infusion, or transplantation, of stem cells is a frequent treatment recommendation for patients with aggressive myelomas. It may be the only recourse if an allogeneic donor is unavailable, but it is more tolerable and associated with better survival than standard allogeneic transplantation. Nevertheless, the outcome is less likely to result in myeloma-free survival because of the uncertainty that the autologous marrow is completely disease free.
• Nonetheless, early autologous transplant, compared with continuation of chemotherapy and delayed transplant in several studies, was associated with a longer symptom-free interval.
• Allogeneic transplant may be recommended for long-term control of disease; however, such an approach is associated with higher morbidity and mortality rates compared to younger patients and those with other diagnoses. Recently, however, there have been a number of clinical trials evaluating the outcomes of patients who have received less intensive, "nonmyeloablative" transplants, sometimes referred to as "mini-transplants." A tissue-compatible family donor is still required for such a procedure, but it is associated with lower mortality rates compared with those of standard allogeneic transplant. The idea behind such an approach is to administer lower doses of chemotherapy to minimize organ damage, and to use allogeneic stem cells to exert an immune reaction against the myeloma, called "graft versus myeloma" effect.

Supportive care

Supportive care is very important in the management of all cancers, and myeloma is no exception. The following issues should be addressed in controlling the complications of the disease:

• Bone stabilization: A class of drugs, the bisphosphonates, is able to slow bone damage, reduce the risk of fractures, and reduce pain due to thinning of bone. They also regulate calcium levels in the blood and possibly affect the immune system in ways that may help fight the myeloma. These drugs are given intravenously, generally once every 3-4 weeks. Examples include pamidronate (Aredia) and zoledronic acid (Zometa). Other bisphosphonates are undergoing development or further evaluation.
• Pain control: Osteolytic lesions and the resulting fractures can cause considerable pain. Patients with myeloma often require pain-reducing medications or radiation to painful lesions.
• Orthopedic care: The fractures from osteolytic damage can cause severe pain and disability. A bone specialist (orthopedist) may provide relief from pain and improve functionality of the affected bones, if necessary. Neurosurgeons, orthopedists, or interventional radiologists may offer a procedure called vertebroplasty (injection of bone cement) to stabilize affected bones in the spine.
• Growth factors: These agents boost production of new blood cells from the bone marrow and aid in recovery from the effects of chemotherapy.

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