• Michael Ozga, Qiuhong Zhao, Don Benson, Patrick Elder, Nita Williams, Naresh Bumma, Ashley Rosko, Maria Chaudhry, Abdullah Khan, Srinivas Devarakonda, Rami Kahwash, Ajay Vallakati, Courtney Campbell, Samir V Parikh, Salem Almaani, Jason Prosek, Jordan Bittengle, Katherine Pfund, Samantha LoRusso, Miriam Freimer, Elyse Redder, Yvonne Efebera, and Nidhi Sharma.
• Division of Hematology, Department. of Internal Medicine, The Ohio State University Comprehensive Cancer Center Columbus, OH, USA.
• Cancer Med. 2021 Feb 1; 10 (3): 965-973.

BackgroundSystemic light chain (AL) amyloidosis is a clonal plasma-cell neoplasm that carries a poor prognosis. Although AL amyloidosis and Multiple Myeloma (MM) can co-exist and share various cytogenetic chromosomal abnormalities, little is known about Fluorescent in situ hybridization (FISH) and its prognostic relevance in AL amyloidosis.AimThe study aims to evaluate the most prevalent FISH cytogenetic abnormalities in AL patients as independent prognostic factors, and assess the impact of cytogenetics on the survival of high-risk cardiac AL patients.Materials & MethodsThis retrospective study reviewed 113 consecutive AL patients treated at The Ohio State University (OSU). Patients were divided into subgroups based on FISH data obtained within 90 days of diagnosis. Hyperdiploidy was defined as trisomies of at least 2 chromosomal loci. Primary endpoints were progression free survival (PFS) and overall survival (OS). Kaplan Meier curves were used to calculate PFS and OS. The log-rank test and Cox proportional hazard models were used to test the equality of survival functions and further evaluate the differences between groups.ResultsFISH abnormalities were detected in 76% of patients. Patients with abnormal FISH trended toward lower overall survival (OS) (p=0.06) and progression free survival (PFS) (p=0.06). The two most prevalent aberrations were translocation t(11;14) (39%) and hyperdiploidy-overall (38%). Hyperdiploidy-overall was associated with worsening PFS (p=0.018) and OS (p=0.03), confirmed in multivariable analysis. Patients with del 13q most frequently had cardiac involvement (p=0.006) and was associated with increased bone marrow plasmacytosis (p=0.02). Cardiac AL patients with no FISH abnormalities had much improved OS (p=0.012) and PFS (p=0.018) CONCLUSIONS: Our findings ultimately reveal the association of hyperdiploidy on survival in AL amyloidosis patients, including the high-risk cardiac AL population.© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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