A Profile of 44 Long Term Survivors (>10yrs) with AL Amyloidosis.
Authors: Wechalekar Ashutosh D. , Lachmann Helen J. , Gillmore Julian D. , Hawkins Philip N. 
Published: October 2019

Abstract
AL amyloidosis has a poor outcome. Survival of only about one year was frequently reported in studies performed in the 1990s, and the diagnosis of AL amyloidosis continues to be widely regarded as incompatible with long term survival. We report here the features of patients with AL amyloidosis followed up at the UK Amyloidosis centre (NAC) for more than 10 years, who encouragingly represented more than 10% of all cases. All patients with AL amyloidosis who first attended the NAC between 1979–1997 and subsequently survived for more than 10 years were included in this study. AL type amyloidosis was confirmed in all patients histologically with genetic studies to robustly exclude hereditary amyloidosis as indicated. Organ involvement and responses were defined as per the international consensus criteria (Gertz et al 2005). I123 serum amyloid P (SAP) scintigraphy was used to identify additional organ involvement and monitor amyloid load. 361 patients with AL amyloidosis were assessed at the NAC before 1st August 1997, with a median survival of 2.4 yrs. 132 (20%) patients survived >5 yrs, and 44 (12%) patients survived >10 years with 2 patients living ≥ 16 yrs and 7 for ≥ 14 yrs. Three patients died at 10.2, 11 and 13 years due to unrelated causes with no deaths due to progressive amyloidosis. Among the 44 ten year survivors, at presentation, median age was 51 yrs (29–70), median creatinine 86μmol/L (47–400), 24 hour proteinuria 2g (<0.1g–50g), bilirubin 8μmol/L (2–130), alkaline phosphatase 82.5 units/L (41–2645), and median NT-ProBNP 19 pMol/L (1–2158). Median ECOG performance status was 1 (0–2). Organ involvement (consensus criteria) was: renal 31 (70%); liver 6 (14%); cardiac 8 (18%); autonomic neuropathy 1(2%); peripheral neuropathy - none; gastrointestinal 2(4%) and lymph nodes or other soft tissues 4 (9%). SAP scintigraphy showed renal amyloid deposits in 30 (68%), liver 11(25%), adrenals 3(7%) and bone infiltration 7 (16%). 35 (79%) had one organ involved, 8 (18%) had 2 organs and 1 (3%) patient had three organs involved by consensus criteria; SAP scintigraphy detected additional organ involvement in 12 cases (27%). The whole body amyloid load on SAP scintigraphy was small in 25(57%), moderate 2 (4%) and large 9 (21%). Median plasma cell infiltrate in the marrow was 5% (1–65). Treatment received comprised an alkylator based regimen in 11(26%), VAD chemotherapy in 14 (32%), and stem cell transplantation (SCT) in 18 (42%). 29 (67%) patients had a complete clonal response, 13 (30%) had a partial response and 1 (2%) had no response. 25(57%) had evidence of organ improvement by conventional criteria and in 26 (59%) SAP scintigraphy showed regression of amyloid. The median time to next treatment (progression free survival - PFS) has not been reached at 10 yrs. There was no significant difference in the PFS between patients treated chemotherapy or SCT, or among the complete or partial responders. 13 patients (30%) developed end stage renal disease (ESRD) a median 5.8 yrs after diagnosis and this was not significantly more frequent among partial responders compared with complete hematologic responders. Substantial improvements in diagnosis, monitoring and treatment of AL amyloidosis have occured since 1997. It is all the more encouraging that we are able to report here that 12% of patients diagnosed before this time survived for more than 10 years and patients with AL amyloidosis diagnosed more recently are likely to have even better prospect of good long term outcome in cases who achieve good and sustained clonal responses to therapy.