Risk Of Progression Of Localised Amyloidosis To Systemic Disease In 606 Patients Over 30 Years
Authors: Mahmood Shameem , Sachchithanantham Sajitha , Bridoux Frank , Lane Thirusha , Rannigan Lisa , Foard Darren , Sayed Rabya , Patel Ketna , Fontanna Marianna , Whelan Carol , Lachmann Helen J , Gillmore Julian D , Hawkins Philip N , Wechalekar Ashutosh 
Published: October 2019

Abstract
Localised AL (light chain) amyloidosis arises due to local formation and deposition of AL amyloid fibrils within a tissue. Little data exists as to the underlying aetiology, biological significance and natural progression of this disease. The primary objective of this study was to evaluate the incidence, clinical course, treatment outcomes and risk of progression to systemic disease.

Methods
This study included all patients with localised amyloidosis assessed at the UK National Amyloidosis centre between 1980 and 2011. Localised amyloidosis was defined as biopsy proven amyloid deposition confined to a single site without any evidence of vital organ involvement (including cardiac, renal, liver, peripheral or autonomic neuropathy) on detailed baseline assessment organ function and no visceral organ uptake on 123I serum amyloid P component (SAP) scintigraphy. Progression to systemic AL was defined as development of new vital organ involvement or dysfunction as by tests of organ function or SAP scintigraphy. Kaplan Meier curves were used to estimate the overall survival (OS); calculated from the start of diagnosis until death or last follow-up.

Results
Six hundred and six patients were diagnosed with localised amyloidosis, accounting for 12% of all newly diagnosed amyloidosis patients during this period at our Centre. The baseline characteristics are given in table 1. The median age was 59.5 years (range 48.8-68.6), 51% were male and median symptom duration was 7 months (range 4-24). All patients had biopsy proven amyloid deposition. Definitive light chain immunostaining for AL kappa or lambda was positive in only 15% while 52% had no immunostaining with antibodies to kappa, lambda, transthyretin or SAA. Three patients had ATTR on bladder biopsy (none with ATTR at other sites) and one with ApoA1 on laryngeal amyloidosis (with ApoA1 Ala164Ser mutation). The sites of localised amyloidosis included: bladder 94 (15%), lung 47 (7.7%), trachea-bronchial 35 (5.7%), larynx/vocal cords - 70 (11.6%), tonsil 4 (0.7%), conjunctiva 12 (2%), orbit 10 (1.7%), lymph nodes 31 (5.1%), GI tract 36 (6%), skin 54 (13.8%) and others. Presenting symptoms depended upon the tissue involved. A serum monoclonal protein was present in 12.5%, with an abnormal kappa/lambda ratio in 13.8%. Therapeutic options for localised disease include surgical procedures (36%), laser therapy (7%), steroids (2%), radiotherapy (2.8% predominantly for amyloidomas/symptom control) and chemotherapy (2.3%; treating amyloid symptoms/disease in 1%, treating co-existing multiple myeloma, lymphoplasmacytic lymphoma and MALT lymphoma in 1.3%). Some patients undergoing surgical procedures had recurrent local amyloid deposition needing repeated procedures. Only one patient out of 606 progressed to systemic AL amyloidosis. This patient presented with mediastinal LN involvement, progressed 5 years following diagnosis, with evidence of new uptake by 123I SAP scintigraphy localised within the spleen and bone marrow infiltration of 10% clonal plasma cells but no abnormal free light chain ratio or presence of a paraprotein. The majority of patients had other co-morbidities with the median age of death 74 years (range 66.5-80). There were no deaths due to progressive amyloidosis. The median follow up was 64 months. The median overall survival (OS) was 69.7 months (range 37.1-130.7) with 2 and 5 year OS 96% and 92% respectively figure 1.

Conclusion
The overall survival of localised AL amyloidosis is excellent and strikingly different from systemic AL amyloidosis. Treatment options are primarily directed locally to the amyloid deposit which is adequate in the majority, with less than satisfactory control and numerous procedures required in some patients, especially those with tracheobronchial amyloidosis, leading to a poor quality of life. Progression to systemic disease is an exceptionally rare occurrence even in presence of a detectable M-protein or abnormal light chain ratio.

Disclosures:
Bridoux: Janssen Cilag: Honoraria; Celgene: Honoraria; Celgene: Research Funding, Research support, Research support Other.