Provincial Health Services Authority (PHSA) improves the health of British Columbians by seeking province-wide solutions to specialized health care needs in collaboration with BC health authorities and other partners.
Revised 25 January 2012
Amyloidosis is a term for diseases where there is extracelluar deposition of pathological insoluble fibrillar proteins in organs and tissues. Amyloid deposits stain with Congo red, appearing red microscopically in normal light but apple green when viewed in polarized light. Under electron microscopy amyloid deposits have a characteristic beta-pleated-sheet configuration.
Amyloidosis can be divided into four major subtypes:
Accurate diagnosis of the amyloid and subtype of amyloid is imperative for proper treatment. AL amyloidosis is a plasma cell dyscrasia (neoplasm) closely related to multiple myeloma with an anticipated incidence of 10 to 20 cases per year in BC.
Patients with AL amyloidosis requiring treatment typically receive chemotherapy whereas chemotherapy would be inappropriate for the other subtypes of amyloidosis. Patients with amyloidosis which is not due to light chains (AL) should be referred to appropriate specialists and do not require treatment or follow up at the BCCA. Given the rarity of AL amyloidosis, patients should be discussed with a member of the Leukemia/BMT Program of BC or a medical oncology member of the Lymphoma Tumour Group at one of the BCCA Centres.
The combination of serum and urine immunofixation with serum free light chain assay approaches 100% sensitivity for identifying a monoclonal protein in patients with AL amyloidosis (Palladini, Clin Chem 2009;55;499-504).
Non-AL amyloidosis should be considered even if a monoclonal immunoglobulin protein is found (Lachman, NEJM 2002; 346:1786-1791). The incidence of MGUS increases with age and the monoclonal protein may be a finding which is unrelated to the diagnosis of amyloid. If the subtype of amyloid remains uncertain after clinical and laboratory assessment, consideration should be made for direct testing of the amyloid by mass spectrometry-based proteomic analysis. Genetic testing may be performed on the peripheral blood should familial amyloidosis be suspected. Although testing for transthyretin amyloid is available in British Columbia (Molecular Genetics Laboratory; C & W Health Center of BC), testing for less common familial amyloid requires sending blood samples to reference laboratories. Direct testing of the amyloid deposit by mass spectrometry-based proteomic analysis remain the most accurate test even in this circumstance.If the amyloidosis is found to be associated with a B-cell neoplasm other than myeloma staging evaluation should be performed as appropriate for the lymphoma.
Cardiac involvement with amyloid is the major determinant of outcome. Cardiac biomarkers have been used to prognosticate patients and determine appropriateness of therapies (particularly high-dose chemotherapy followed by stem cell rescue) (Dispenzieri, Blood, 2004;104:1881-1887). Using threshold values of Troponin < 0.035μg/L and NT-proBNP < 332 ng/L:
All patients should receive the immunizations recommended in Appendix III.
For older or unfit patients who are not eligible for transplantation, a bortezomib based treatment (UMYMPBOR) (Kastritis J Clin Onc, 2010;28:1031-1037) or melphalan with dexamethasone is used (Palladini Blood, 2004;103:2936-2938). Younger, fit patients (up to approximately 70 years of age) may be offered high dose chemotherapy and autologous hematopoietic stem cell transplant. Such patients should NOT be treated with melphalan prior to stem cell collection as it may affect the ability to collect adequate amounts of stem cells to support transplantation.
The Bone Marrow Transplantation Team offers treatment with high dose chemotherapy and hematopoietic stem cell transplantation to selected patients depending upon the level of organ dysfunction and cardiac involvement (Sanchorawala Blood, 2007;110:3561-3563). Physicians with potentially eligible patients should initiate referral with a member of the Bone Marrow Transplant Team. Induction chemotherapy may be considered with a bortezomib containing regimen (UMYBORPRE) but may not be necessary. Patients who are candidates for high dose chemotherapy and hematopoietic stem cell transplantation should NOT be treated with melphalan or other alkylating agents because this may make it impossible to gather adequate stem cells to support transplantation.
Secondary treatments for recurrent AL amyloid may include the following:
Currently evidence for second line treatment is limited but options remain similar to that available for myeloma. The choice of the timing and order of these drugs must be individualized.
Radiation may be useful for symptomatic focal lesions which will stop progressing if irradiated but often do not regress.
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