DESCRIPTION
Primary Systemic Amyloidosis
Primary systemic amyloidosis is a plasma cell disorder that causes extracellular deposition of insoluble protein (usually light-chain immunoglobulins) in critical organs and tissues such as the heart, liver, kidneys, gastrointestinal tract, spleen, or nervous system. Progressive protein accumulation impairs organ function and results in organ failure and death when treatment is unsuccessful. Primary amyloidosis is not a malignancy, although it is related to multiple myeloma, which is also a plasma cell disorder. Clonal plasma cells are found in the marrow of patients with either disease. However, in those with primary amyloidosis, the proportion of marrow cells that are plasma cells does not change much with time.
High-Dose Chemotherapy
High-dose chemotherapy (HDC) involves the administration of cytotoxic agents using doses several times greater than the standard therapeutic dose. In some cases, whole body or localized radiotherapy is also given and is included in the abbreviation HDC when applicable. The most significant adverse effect of HDC is marrow ablation. Thus, HDC is followed by infusion of hematopoietic stem cells to repopulate the bone marrow.
Stem-Cell Transplant
Autologous hematopoietic stem cells are those harvested from the patient prior to myeloablative therapy. Allogeneic hematopoietic stem cells are those harvested from a donor.
Hematopoietic stem cells can be collected from either the bone marrow or the peripheral blood of patients. Stem cells may be harvested from the peripheral blood using a pheresis procedure. To increase the number of stem cells in the peripheral circulation (termed mobilization), patients providing autologous blood stem cells are pretreated with a course of chemotherapy or hematopoietic growth factors, or both.
POLICY
High-dose chemotherapy with autologous stem-cell support for the treatment of primary AL amyloidosis is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
See also:
MEDICAL APPROPRIATENESS
High-dose chemotherapy with autologous stem-cell support for the treatment of primary AL amyloidosis is considered medically appropriate if ALL of the following criteria are met:
Amyloid deposition in two or fewer organs
Left ventricular ejection fraction (LVEF) greater than 45%
ADDITIONAL INFORMATION
There are three major categories of amyloidosis:
Primary Amyloid Light-chain (AL) amyloidosis
Secondary or Amyloid A (AA) amyloidosis
Familial or hereditary (AI) amyloidosis
Primary AL amyloidosis is the most common and it is the only form of amyloidosis known to benefit from autologous stem-cell transplantation.
Tandem is defined as two or more courses of high-dose chemotherapy and stem-cell transplantation. Although evidence supports this as a treatment for Multiple Myeloma, research is limited in support for primary AL amyloidosis.
SOURCES
Amyloidosis Foundation. (2004, October). What is Amyloidosis? Retrieved March 17, 2008 from http://www.amyloidosis.org/whatisit.asp.
BlueCross BlueShield Association. Medical Policy Reference Manual. (5:2007). High-Dose Chemotherapy plus Hematopoietic Stem-Cell support to Treat Primary Amyloidosis or Waldenstrom’s Macroglobulinemia. (8.01.42). Retrieved March 12, 2008 from BlueWeb. (19 articles and/or guidelines reviewed)
Chow, L. Q., Bahlis, N., Russell, J., Chaudhry, A., Morris, D., Brown, C., et al. (2005). Autologous transplantation for primary systemic AL amyloidosis is feasible outside a major amyloidosis referral centre: The Calgary BMT program experience. Bone Marrow Transplantation, 36 (7), 591-596. (Level 4 Evidence)
Mollee, P., N., Wechalekar, A., D., Pereira, D., L., Franke, N., Reece, D., Chen, C., et al. (2004). Autologous stem cell transplantation in primary systemic amyloidosis: The impact of selection criteria on outcome. Bone Marrow Transplantation, 33 (3), 271-277. (Level 4 Evidence)
National Guideline Clearinghouse. (2004, June). Guidelines on the diagnosis and management of AL amyloidosis. Retrieved April 15, 2008 from http://www.guideline.gov/summary/summary.aspx?doc_id=9558&nbr=005103&string=amyloidosis.
Sanchorawala, V., Wright, D. G., Seldin, D. D., Dember, L. M., Finn, K., Falk, R. H., et al. (2001). An overview of the use of high-dose melphalan with autologous stem cell transplantation for the treatment of AL amyloidosis. Bone Marrow Transplantation, 28 (7), 637-642. (Level 4 Evidence)
Sanchorawala, V., Wright, D., G., Seldin, D., C., Falk, R., H., Finn, K., T., Dember, L., M., et al. (2004). High-dose intravenous melphalan and autologous stem cell transplantation as initial therapy or following two cycles of oral chemotherapy for the treatment of AL amyloidosis: Results of a prospective randomized trial. Bone Marrow Transplantation, 33 (4), 381-388. (Level 2 Evidence - Industry sponsored)
Skinner, M., Sanchorawala, V., Seldin, D., C., Dember, L., M., Falk, R., H., Berk, J., L., et al. (2004). High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: An 8-year study. Annals of Internal Medicine, 140 (2), 85-93. (Level 2 Evidence - Industry sponsored)
U.S. Department of Health & Human Services. Centers for Medicare & Medicaid Services. National Coverage Analyses. (January, 2006). NCD for Stem Cell Transplantation (110.8.1). Retrieved March 14, 2008 from http://www.cms.hhs.gov/mcd/viewncd.asp?ncd_id=110.8.1&ncd_version=4&basket=ncd%3A110%2E8%2E1%3A4%3AStem+Cell+Transplantation.
Worel, N., Schulenburg, A., Mitterbauer, M., Keil, F., Rabitsch, W., Kalhs, P. (2006). Autologous stem-cell transplantation in progressing amyloidosis is associated with severe transplant-related toxicity. Wiener Klinische Wonchenschrif, 118 (1-2), 49-53. (Level 4 Evidence)
ORIGINAL EFFECTIVE DATE: 9/14/2008
MOST RECENT REVIEW DATE: 9/14/2008
ID_BT
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