BlueCross BlueShield of Tennessee Medical Policy Manual

High Dose Chemotherapy with Autologous Stem-Cell Transplant for Primary Amyloid Light-Chain (AL) Amyloidosis

DESCRIPTION

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 (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.

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:

• Autologous Hematopoietic Stem-Cell Transplantation for Malignant Astrocytomas and Gliomas

• Donor Lymphocyte Infusion for Hematologic Malignancies Treated with an Allogeneic Hematopoietic Stem Cell Transplant

• Hematopoietic Stem Cell Transplant for Breast Cancer

• Hematopoietic Stem Cell Transplantation for Central Nervous System Embryonal and Ependymoma Tumors

• Hematopoietic Stem-Cell Transplantation for Miscellaneous Solid Tumors in Adults

• Hematopoietic Stem Cell Transplantation in the Treatment of Germ Cell Tumors

• High Dose (Myeloablative) Chemotherapy with Bone Marrow, Peripheral Stem Cell, or Cord Blood Transplant for Hematopoietic Stem Cell Support

• Nonmyeloablative Allogeneic Stem Cell Transplantation (Reduced Intensity Stem Cell Transplant) for Treatment of Malignancy

• Pancreas / Pancreas-Kidney / Pancreatic Islet Cell Transplantation

• Tandem High Dose Chemotherapy with Hematopoietic Stem Cell Support

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:

1. • Amyloid deposition in two or fewer organs

   • Left ventricular ejection fraction (LVEF) greater than 45%

IMPORTANT REMINDERS

• Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.

• We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

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. Higher Treatment Related Mortality (TRM) has been associated with high dose chemotherapy and stem cell transplant in individuals with dominant or symptomatic cardiac amyloid and in individuals with greater than 2 organ systems involved.

Tandem is defined as two or more courses of high-dose chemotherapy and stem-cell transplantation. Although evidence supports this as a treatment in other disease processes, research is limited in support for primary AL amyloidosis.

SOURCES

Amyloidosis Foundation. (2009, November). AL Amyloidosis.  Retrieved March 9, 2010 from http://www.amyloidosis.org/treatment/primary.asp#primary.

BlueCross BlueShield Association. Medical Policy Reference Manual. (8:2009). High-Dose Chemotherapy plus Hematopoietic Stem-Cell support to Treat Primary Amyloidosis or Waldenstrom’s Macroglobulinemia. (8.01.42). Retrieved October 9, 2010 from BlueWeb. (24 articles and/or guidelines reviewed)

Complete Guide to Medicare Coverage Issues [Computer software]. (2009, November). Stem Cell Transplantation (NCD110.8.1, p. 2-53). Ingenix.

Hoffman, R., Benz, E., Shattil, S., Furie, B., Silberstein, L., McGlave, P., et al. (2008). Hematology: Basic Principles and Practice (5th ed., chapter 89). Philadelphia: Churchill Livingstone Elsevier.

National Cancer Institute. (2010, July). Multiple myeloma and other plasma cell neoplasms treatment PDQ. Retrieved October 8, 20120 from http://www.nccn.org/professionals/physician_gls/PDF/myeloma.pdf.

National Comprehensive Cancer Network. (2010). Multiple Myeloma. Retrieved October 10, 2010 from http://www.nccn.org/professionals/physician_gls/PDF/myeloma.pdf.

National Guideline Clearing House. British Journal of Haemotology. (2004, June). Guidelines on the diagnosis and management of AL amyloidosis. Retrieved October 10, 2010 from http://www.amyloidosis.org/download/BJH_Guidlines_for_Amyloidosis.pdf.

Perfetti, V., Siena, S., Palladini, G., Bregni, M., DiNicola, M., Obici, L., et al. (2006). Long term results of a risk adapted approach to melphalan conditioning in autologous peripheral blood stem cell transplantation for primary (AL) amyloidosis. The Hematology Journal, 91 (12), 1635-1643. (Level 3 Evidence)

Vesole, D., Perez, W., Akasheh, M., Boudreau, C., Reece, D., & Bredeson, C. (2006, July) High-dose therapy and autologous stem cell transplantation for the patient with primary systemic amyloidosis: A Center for International Blood and Marrow Transplant Research study. Mayo Clinic Proceedings, 81 (7), 880-888. (Level 1 Evidence)

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:  12/9/2010  

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Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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