The levels of evidence (I–IV) and strength of recommendations (A–C) are defined at the end of the "Major Recommendations" field.

Diagnosis and Investigation

• Maintain a high index of suspicion (grade B recommendation, level III evidence)
• Confirm the presence of amyloid on a tissue biopsy (grade B recommendation, level III evidence)
• Look for evidence of plasma cell dyscrasias including immunofixation and serum free light chain (FLC) measurements (grade B recommendation, level III evidence)
• Consider discussion with/referral to National Amyloidosis Centre (NAC) for exclusion of other forms of amyloidosis (grade B recommendation, level III evidence)
• Perform comprehensive assessment of the extent of organ involvement by non-invasive criteria including serum amyloid P component (SAP) scanning when this is feasible (grade B recommendation, level III evidence)

Investigations required in suspected AL amyloidosis

Chemotherapy and Other Agents

Colchicine

• There is no role for colchicines in the management of AL amyloidosis (grade A recommendation, level Ib evidence)

Melphalan and Prednisolone

• Melphalan with or without prednisolone may be considered as initial treatment of choice for patients in whom intermediate or high-dose therapy (HDT) is not considered appropriate (grade A recommendation; level Ib evidence).
• Treatment should be continued when feasible until the clonal disease has been substantially suppressed (i.e. by at least 50–75%, or until plateau) and should be monitored where possible by the serum FLC assay (grade C recommendation; level IV evidence)
• The evidence of benefit from steroids in standard doses has not been evaluated in AL amyloidosis. In myeloma the evidence of benefit from steroids in standard doses is controversial. It may therefore be reasonable not to include prednisolone, particularly in patients at risk of steroid-related side effect (grade C recommendation; level IV evidence).

Combination Chemotherapy

• There is no role for the use of VBMCP (vincristine, carmustine, melphalan, cyclophosphamide, prednisone) in the management of AL amyloidosis (grade A recommendation; level Ib evidence).
• There is no evidence to support the use of other alkylator-based combination regimens such as ABCM (adriamycin, bleomycin, cyclophosphamide, mitomycin-C) or VMCP (vincristine, melphalan, cyclophosphamide, prednisone)-VBAP (vincristine, carmustine, adriamycin, prednisone).

Interferon (IFN)-alpha2b

• There is no role for the use of IFN-alpha2b in the management of AL amyloidosis (grade B recommendation; level IIa evidence).

Vincristine, Adriamycin, Dexamethasone (VAD)

• VAD should be considered as first-line therapy in patients under the age of 70 years who do not have symptomatic cardiac failure, autonomic neuropathy or peripheral neuropathy (grade B recommendation; level III evidence).
• Careful monitoring is required because of increased risk of toxicity in these patients (grade C recommendation; level IV evidence).

High-Dose Pulsed Dexamethasone (HDD)

• HDD may be considered in patients in whom other regimens may not be feasible due to expected toxicity or in those who are refractory to chemotherapy (grade B recommendation; level IIa evidence).

Intermediate-Dose Melphalan (IDM)

• Intermediate dose melphalan may be considered in patients who are fit for intravenous therapy, but in whom VAD is contraindicated or has produced an inadequate response (grade C recommendation; level III evidence).
• Stem cell harvesting prior to treatment with IDM should be considered in patients who might subsequently benefit from peripheral blood stem cell transplantation (PBSCT) as the IDM regimen may deplete stem cell reserves (grade C recommendation; level IV evidence).

Thalidomide

• Thalidomide may be considered in patients in whom other regimens may not be feasible due to expected toxicity or in those who are refractory to chemotherapy (grade C recommendation; level IV evidence).
• Where possible, patients should be treated in the context of clinical trials (grade C recommendation; level IV evidence).

HDT and Autologous Stem Cell Transplantation

• High-dose therapy and PBSCT is not recommended in patients with any of the following:
  • Symptomatic cardiac amyloid
  • Symptomatic autonomic neuropathy
  • History of gastrointestinal bleeding due to amyloid
  • Dialysis-dependent renal failure
  • Age over 70 years
  • More then two organ systems involved
• Peripheral blood stem cell transplantation may be considered in other selected patients, including:
  • Good-risk patients (no cardiac involvement, one to two organs involved and glomerular filtration rate >50 ml/min)
  • Patients treated with VAD or other initial therapy who have not responded
  • Patients with early relapse of plasma cell dyscrasia after VAD or other treatment
• Transplantation should be performed according to an agreed protocol in centres with particular expertise/ interest caution is required during mobilization and harvesting of stem cells prior to transplantation and this should also be performed according to an agreed protocol in  centres with particular expertise/interest.

Overview of Treatment

• Present recommendations for choice of therapy are as follows:
  • Where possible, patients should be treated in the context of clinical trials.
  • Patients who are fit enough should receive VAD as initial therapy.
  • IDM should be considered in patients who are fit for intravenous therapy, but in whom VAD is contraindicated or has produced an inadequate response. PBSC harvest should be considered before proceeding with IDM.
  • If not fit for VAD or IDM, the treatment options are as follows, but the evidence base is very small and there have been no comparative, randomized, controlled trials. No firm recommendation can therefore be made, and treatment choice will depend on individual factors.
    • Melphalan and prednisolone (MP): well-tolerated but slow response
    • HDD: rapid response but no data on durability
    • Thalidomide: more data needed
    • Novel therapies
    • Palliative care
  • High-dose therapy and PBSCT may be considered in selected patients (see above).
  • Supportive care is important in all patients.

General Supportive Care and Organ Transplantation

Renal Failure and Renal Transplantation

• Patients with end-stage renal failure should be considered for dialysis (grade C recommendation; level IV evidence).
• Renal transplantation may be considered in selected patients on a case-by-case basis (grade C recommendation; level IV evidence).

Congestive Cardiac Failure and Cardiac Transplantation

• Congestive cardiac failure should be treated predominantly with diuretics, and angiotensin-converting enzyme inhibitors should be used with caution (grade C recommendation; level IV evidence).
• Calcium-channel blockers and beta-blockers are best avoided in cardiac amyloidosis (grade C recommendation; level IV evidence).
• Cardiac amyloidosis is a relative contraindication to the use of digoxin (grade C recommendation; level IV evidence).
• In patients where cardiac manifestations are the predominant or only signs/symptoms of cardiac amyloidosis, patients should be considered for heart transplantation but this procedure should be followed by chemotherapy treatment to prevent re-accumulation of amyloid in the transplanted heart (grade C recommendation; level IV evidence).

Orthostatic Hypotension

• Orthostatic hypotension may respond to use of support stockings coupled with modest doses of fludrocortisone (grade C recommendation; level IV evidence).
• Midodrine is the most effective drug for orthostatic hypotension in patients with amyloidosis, but can cause supine hypertension (grade C recommendation; level IV evidence)

Bleeding

• There are no evidence-based recommendations for the management of bleeding in patients with amyloidosis (grade C recommendation; level IV evidence).
• Conventional supportive therapy should be considered. This may include factor replacement where coagulation assays indicate a need and platelet transfusion when the platelet count suggests that thrombocytopenia might be making a contribution to the bleeding. In addition, anti-fibrinolytic agents and local measures to secure haemostasis may be employed (grade C recommendation; level IV evidence.
• A conservative approach to surgery is recommended, and biopsies should not routinely be used to document the extent of organ involvement after the initial diagnosis has been made. Liver biopsies are best avoided, or made via the trans-jugular route (grade C recommendation; level IV evidence.
• There are anecdotal reports of resolution of clotting abnormalities following treatment with chemotherapy and splenectomy but these are not substantive enough to form the basis of a clear recommendation (grade C recommendation; level IV evidence.

Experimental Approaches to Treatment

Future Directions

• Where possible patients receiving new therapies should be treated in the context of clinical trials (grade C recommendation; level IV evidence).

Multiple Myeloma and AL Amyloidosis

• Where myeloma and AL amyloidosis co-exist, choice of treatment for myeloma should take into account the extent of organ involvement with amyloid and the potential toxicities of individual treatments (grade C recommendation; level IV evidence).

Patient Information and Support

The National Guideline Clearinghouse™ (NGC) does not develop, produce, approve, or endorse the guidelines represented on this site.

All guidelines summarized by NGC and hosted on our site are produced under the auspices of medical specialty societies, relevant professional associations, public or private organizations, other government agencies, health care organizations or plans, and similar entities.