Impact of Chromosomal Abnormalities Revealed by Interphase FISH on Survival in Primary Light Chain Amyloidosis.
Authors: Wechalekar Ashutosh , Orchard Kim , Lachmann Helen , Ross Fiona , Hawkins Philip , Harrison Christine 
Published: April 2020

Primary light chain amyloidosis (AL) is associated with a subtle monoclonal plasma cell population. Due to the small percentage and low mitotic index of these abnormal plasma cells, cytogenetic studies in AL have been restricted to analysis by interphase fluorescence in situ hybridization (iFISH), with published reports of &lt;100 patients. In a recent iFISH study we reported the incidence and clinical associations of chromosomal abnormalities involving the IgH locus and deletions of chromosome 13, del(13), in a series of 32 AL patients from the National Amyloidosis Centre, UK (Harrison, et al, 2002, Br. J. Haematol. 117, 427–435). In this present study, we have reviewed the clinical details, including survival data, on the same patient cohort in order to investigate the impact of specific chromosomal changes on survival in AL. Follow-up information was available on 30 of the initial 32 patients: Median age at presentation was 59 years (range 40–83 years); the male to female ratio was 1.7:1; 24 patients had systemic and six had localized AL (bladder n=3, lymph node n=1, lung n=1). Due to a markedly different disease course, patients with localized AL are excluded from the survival analysis. 27 (90%) patients had serum free light chains while nine (30%) had intact paraprotein. SAP scintigraphy showed organ involvement as: liver n=12 (40%), spleen n=18 (60%), kidneys n=12 (40%) (including 7 with renal failure) and heart (by echocardiography) n= 14 (46%). 15 (50%) patients had ≥ 5% plasma cells in the bone marrow. Chromosomal abnormalities were detected in 16 (53%) patients with systemic AL (none were found in localized AL) of which 75% occurred in patients with ≥ 5% plasma cells. Ten (33%) patients had del(13) (8 patients with &gt;5% plasma cells); 12 (40%) patients had IgH translocations: t(11;14)(q13;q32) n=10 (33%) (7 in patients with &gt;5% plasma cells); unknown translocation partner n=2 (6%). Treatment data was available for seven patients: six (20%) had combination chemotherapy of which 3 (50%) were responders and three (10%) had successful autologous PBSCT. There was no association of any specific chromosomal abnormality with the pattern of organ involvement or response to treatment. Median follow-up was 22 months. Median overall survival (OS) of patients with systemic AL was 11 months (range 2–61). There was a difference, although not to statistically significant levels, between patients with chromosomal abnormalities compared to those without [median OS 7 months (range 2–61) vs. 14 months (range 2–42); p= 0.34], in particular, for patients with del(13) [7 months (range 2–61) vs. 15 months (range 2–42); p=0.28]. t(11;14) did not appear to impact survival[median OS 12 months (range 2–61) vs.11 months (range 2–42); p=0.43]. In conclusion, chromosomal abnormalities appear to be more frequent in AL patients with ≥ 5% plasma cells in their bone marrow. Presence of any chromosomal abnormality and specifically del(13) are associated with a trend towards a poorer outcome. A larger study is in progress to further investigate these observations.