Immunoglobulin light chain amyloidosis: 2016 update on diagnosis, prognosis, and treatment

Abstract

All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure of involved sites. Stem cell transplant (SCT) is preferred, but only 20% of patients are eligible. Requirements for safe SCT include systolic blood pressure >90 mmHg, troponin T <0.06 ng mL21, age <70 years, and serum creatinine 1.7 mg dL21. Nontransplant candidates can be offered melphalan-dexamethasone or cyclophosphamide-bortezomib-dexamethasone. Other combinations of chemotherapy with agents such as cyclophosphamide-thalidomide (or lenalidomide)-dexamethasone, bortezomib-dexamethasone, and melphalan-prednisone-lenalidomide have documented activity. Antibodies designed to dissolve existing amyloid deposits are under study for previously treated and untreated patients. Late diagnosis remains a major obstacle to initiating effective therapy. Am. J. Hematol., 2016. © 2016 Wiley Periodicals, Inc. Am. J. Hematol. 91:948-956, 2016. © 2016 Wiley Periodicals, Inc.

Dysphagia unveiling systemic immunoglobulin light-chain amyloidosis with multiple myeloma

“…Ninety-one per cent of patients with GI amyloidosis also have concomitant renal amyloid deposits, as found in our case 14. For identifying the type of amyloid deposits, mass spectrometry is superior to immunohistochemistry, and is considered to be the standard to confirm protein composition of amyloid deposits 2. Confirmation of organ involvement by AL amyloidosis is an indication for treatment of any underlying monoclonal gammopathy 4…”

“…AL amyloidosis is characterised by the clonal expansion of BM plasma cells that produce a monoclonal light chain of kappa or lambda variety as either intact molecules or their fragments 2. The epidemiology of amyloidosis is difficult to describe because of its rareness and delay in diagnosing due to wide spectrum of aetiologies and manifestations.…”

“…Diagnosis of AL amyloidosis should be suspected in the presence of unexplained fatigue, oedema or weight loss in patients with monoclonal gammopathy 2. If suspected, immunofixation of serum and urine FLC assay should be obtained 12.…”

“…If suspected, immunofixation of serum and urine FLC assay should be obtained 12. The high frequency of kappa IgG FLC proteinaemia is a hallmark of AL amyloidosis 2. After the former has been established, the tissue diagnosis of amyloidosis is needed.…”

Diagnosis of amyloid neuropathy

“…hATTR has been reported throughout the world, particularly in Europe, with marked phenotypic heterogeneity 1. TTR is primarily synthesised in the liver and misfolding of the ATTR protein causes aggregation and formation of insoluble amyloid fibrils that deposit systemically 2.…”