Amyloidosis involves extracellular deposition of abnormal proteins/fibrils with potential end organ damage. AL type amyloidosis is one subtype and a clonal plasma cell disorder.
A 74-year-old completely asymptomatic male presented with progressive renal dysfunction. Work up with serum protein electrophoresis (SPEP) and immunofixation revealed monoclonal IgG Lamda spike of 1.1 g/dL. Urine protein electrophoresis noted Bence Jones proteins. Notable labs, hemoglobin 10.6 g/dL, calcium was 8.2 mg/dL, and creatinine 2.4 mg/dL. Quantitative immunoglobulins IgA, IgG, and IgM, were 59 mg/dL, 1,939 mg/dL, and 23 mg/dL, respectively. Lambda and Kappa free light chains 26.37 mg/L and 127.87 mg/L, respectively, with a ratio of 0.21. Skeletal survey noted a 4 mm lucency of the left frontal bone. Bone marrow biopsy confirmed 21% plasma cells. Renal biopsy revealed AL lambda light chain confirming final diagnosis AL Lambda light chain Amyloidosis and IgG Lambda Multiple Myeloma. Treatment with daratumumab, cyclophosphamide, bortezomib, and dexamethasone initiated. His clinical course was complicated by COVID 19 infection prior to treatment initiation and with congestive heart failure secondary to cardiac amyloidosis (elevated Troponin and Brain Natriuretic Peptide level) during induction therapy requiring hospitalization, diuresis and optimization of cardiac medications. Very Good Partial Response (VGPR) noted after 2 cycles and near Complete Response (CR) after 4 cycles. Patient was evaluated and approved for Stem cell transplant (SCT) but decided against SCT and has now proceeded to single agent daratumumab maintenance.
Amyloidosis is an uncommon disease seen in older adults (median age 64) with deposition of fibrils composed of low molecular weight subunits derived from normal proteins. Various subtypes and protien/fibrils include AL amyloidosis (immunoglobulin light chain), hereditary/ familial transthyretin amyloidosis (mutated transthyretin, apolipoprotien, fibrinogen A, lysozyme), wildtype transthyretin Amyoidosis/senile amyloidosis (unmutated transthyretin) and AA amyloidosis (serum amyloid A fibril). AL amyloidosis is a systemic disorder that presents with nephrotic syndrome or restrictive cardiomyopathy (as in this case). Other presentations involve peripheral neuropathy, hepatomegaly, macroglossia, arthropathy with “shoulder pad” sign, bleeding diathesis, purpura including “racoon eyes”. Biopsy of the affected organ (kidney, liver, fat pad aspirate, bone marrow) with Congo red staining confirms the histologic diagnosis. Amyloid light chains can be confirmed with proteomic analysis (mass spectrometry or immuno-electron-microscopy).
AL amyloidosis treatment entails high dose chemotherapy and autologous SCT. Long term prognosis in advanced stage is poor. Survival can be short (4-6 months), heart failure causing about 50% of deaths. Daratumumab-regimens offer a 40-55% CR and with SCT data (83% five year and 50% ten-year survival) the outlook is improving.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:asrf-1892 |
| Date | 07 April 2022 |
| Creators | Kim, James, Pham, Thi Le Na, Singal, Sakshi, Jaishankar, Devapiran |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | Appalachian Student Research Forum & Jay S. Boland Undergraduate Research Symposium |
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