Yang Yu1, Niquelle Brown Wade1, Amie E Hwang1, Ajay K Nooka2, Mark A Fiala3, Ann Mohrbacher4, Edward S Peters5, Karen Pawlish6, Cathryn Bock7, David J Van Den Berg1, Kristin A Rand8, Daniel Stram8, David V Conti1, Daniel Auclair9, Graham A Colditz3, Jayesh Mehta10, Christopher A Haiman1, Howard Terebelo11, Nalini Janakiraman12, Seema Singhal10, Brian Chiu13, Ravi Vij3, Leon Bernal-Mizrachi14, Jeffrey A Zonder7, Carol A Huff15, Sagar Lonial2, Robert Z Orlowski16, Wendy Cozen1,17, Sikander Ailawadhi18. 1. Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA. 2. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA. 3. Division of Oncology, Washington University School of Medicine, Saint Louis, MO. 4. Department of Medicine, Division of Hematology, University of Southern California, Los Angeles, CA. 5. Louisiana State University School of Public Health, New Orleans, LA. 6. New Jersey Department of Health, Trenton, NJ. 7. Karmanos Cancer Center, Wayne State University, Detroit, MI. 8. Ancestry.com, San Francisco, CA. 9. Multiple Myeloma Research Foundation, Norwalk, CT. 10. Feinberg School of Medicine, Northwestern University, Chicago, IL. 11. Providence Hospital, Southfield, MI. 12. Division of Hematology-Oncology, Henry Ford Hospital, Detroit, MI. 13. Department of Public Health Sciences, University of Chicago, Chicago, IL. 14. Grady Memorial Hospital, Emory University, Atlanta, GA. 15. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD. 16. Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX. 17. Department of Pathology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA. 18. Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL.
Abstract
PURPOSE: Multiple myeloma (MM) treatment has changed tremendously, with significant improvement in patient out-comes. One group with a suboptimal benefit is patients with high-risk cytogenetics, as tested by conventional karyotyping or fluorescence in situ hybridization (FISH). Methodology for these tests has been published, but not necessarily standardized. METHODS: We address variability in the testing and reporting methodology for MM cytogenetics in the United States using the ongoing African American Multiple Myeloma Study (AAMMS). We evaluated clinical and cytogenetic data from 1,221 patients (1,161 with conventional karyotyping and 976 with FISH) tested between 1998 and 2016 across 58 laboratories nationwide. RESULTS: Interlab and intralab variability was noted for the number of cells analyzed for karyotyping, with a significantly higher number of cells analyzed in patients in whom cytogenetics were normal (P 5.0025). For FISH testing, CD138-positive cell enrichment was used in 29.7% of patients and no enrichment in 50% of patients, whereas the remainder had unknown status. A significantly smaller number of cells was analyzed for patients in which CD138 cell enrichment was used compared with those without such enrichment (median, 50 v 200; P, .0001). A median of 7 loci probes (range, 1-16) were used for FISH testing across all laboratories, with variability in the loci probed even within a given laboratory. Chromosome 13-related abnormalities were the most frequently tested abnormality (n5956; 97.9%), and t(14;16) was the least frequently tested abnormality (n 5 119; 12.2%). CONCLUSIONS: We report significant variability in cytogenetic testing across the United States for MM, potentially leading to variability in risk stratification, with possible clinical implications and personalized treatment approaches.
PURPOSE:Multiple myeloma (MM) treatment has changed tremendously, with significant improvement in patient out-comes. One group with a suboptimal benefit is patients with high-risk cytogenetics, as tested by conventional karyotyping or fluorescence in situ hybridization (FISH). Methodology for these tests has been published, but not necessarily standardized. METHODS: We address variability in the testing and reporting methodology for MM cytogenetics in the United States using the ongoing African American Multiple Myeloma Study (AAMMS). We evaluated clinical and cytogenetic data from 1,221 patients (1,161 with conventional karyotyping and 976 with FISH) tested between 1998 and 2016 across 58 laboratories nationwide. RESULTS: Interlab and intralab variability was noted for the number of cells analyzed for karyotyping, with a significantly higher number of cells analyzed in patients in whom cytogenetics were normal (P 5.0025). For FISH testing, CD138-positive cell enrichment was used in 29.7% of patients and no enrichment in 50% of patients, whereas the remainder had unknown status. A significantly smaller number of cells was analyzed for patients in which CD138 cell enrichment was used compared with those without such enrichment (median, 50 v 200; P, .0001). A median of 7 loci probes (range, 1-16) were used for FISH testing across all laboratories, with variability in the loci probed even within a given laboratory. Chromosome 13-related abnormalities were the most frequently tested abnormality (n5956; 97.9%), and t(14;16) was the least frequently tested abnormality (n 5 119; 12.2%). CONCLUSIONS: We report significant variability in cytogenetic testing across the United States for MM, potentially leading to variability in risk stratification, with possible clinical implications and personalized treatment approaches.
Authors: Andrew Ip; Alexandra Della Pia; Gee Youn Geeny Kim; Jason Lofters; James Behrmann; Dylon Patel; Simone Kats; Jeffrey Justin Estella; Ivan De Dios; Wanlong Ma; Andrew L Pecora; Andre H Goy; Jamie Koprivnikar; James K McCloskey; Maher Albitar Journal: Front Oncol Date: 2022-06-14 Impact factor: 5.738
Authors: Parvathi Sudha; Aarif Ahsan; Karthik Ramasamy; Anjan Thakurta; Brian A Walker; Cody Ashby; Tasneem Kausar; Akhil Khera; Mohammad H Kazeroun; Chih-Chao Hsu; Lin Wang; Evelyn Fitzsimons; Outi Salminen; Patrick Blaney; Magdalena Czader; Jonathan Williams; Mohammad I Abu Zaid; Naser Ansari-Pour; Kwee L Yong; Frits van Rhee; William E Pierceall; Gareth J Morgan; Erin Flynt; Sarah Gooding; Rafat Abonour Journal: Clin Cancer Res Date: 2022-07-01 Impact factor: 13.801