1. A longitudinal analysis of chromosomal abnormalities in disease progression from MGUS/SMM to newly diagnosed and relapsed multiple myeloma
- Author
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Elona Saraci, Marina Ruggeri, Gloria Margiotta Casaluci, Milena Gilestro, Daniela Oddolo, Stefania Oliva, Elisa Genuardi, Paola Omedè, Rossella Troia, S. Caltagirone, Roberto Mina, Lorenzo De Paoli, Sara Bringhen, Mario Boccadoro, and Mattia D'Agostino
- Subjects
Male ,Smoldering Multiple Myeloma ,medicine.medical_treatment ,Gastroenterology ,Monoclonal Gammopathy of Undetermined Significance ,Leukemia, Plasma Cell ,0302 clinical medicine ,Multiple myeloma ,Risk Factors ,Medicine ,Chromosomes, Human ,Longitudinal Studies ,Cytogenetic abnormalities ,Plasma cell leukemia ,Leukemia ,Hematology ,medicine.diagnostic_test ,Fluorescence in situ hybridization ,General Medicine ,Middle Aged ,Survival Rate ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Plasma Cell ,Female ,Human ,medicine.medical_specialty ,Chromosomes ,Disease-Free Survival ,Clonal Evolution ,03 medical and health sciences ,FISH ,Internal medicine ,Humans ,Aged ,Retrospective Studies ,Chromosome Aberrations ,Disease progression ,Chemotherapy ,business.industry ,medicine.disease ,Clonal evolution ,Follow-Up Studies ,Bone marrow ,business ,Progressive disease ,Monoclonal gammopathy of undetermined significance ,030215 immunology - Abstract
We analyzed variations in terms of chromosomal abnormalities (CA) by fluorescence in situ hybridization (FISH) analysis on purified bone marrow plasma cells throughout the progression from monoclonal gammopathy of undetermined significance/smoldering multiple myeloma (MGUS/SMM) to newly diagnosed MM/plasma cell leukemia (NDMM/PCL) at diagnosis and from diagnostic samples to progressive disease. High risk was defined by the presence of at least del(17p), t(4;14), and/or t(14;16). 1p/1q detection (in the standard FISH panel from 2012 onward) was not available for all patients. We analyzed 139 MM/PCL diagnostic samples from 144 patients, with a median follow-up of 71 months: high-risk CA at diagnosis (MGUS/SMM or NDMM) was present in 28% of samples, whereas 37–39% showed high-risk CA at relapse. In 115 patients with NDMM who evolved to relapsed/refractory MM, we identified 3 different populations: (1) 31/115 patients (27%) with gain of new CA (del13, del17p, t(4;14), t(14;16) or 1q CA when available); (2) 10/115 (9%) patients with loss of a previously identified CA; and (3) 74 patients with no changes. The CA gain group showed a median overall survival of 66 months vs. 84 months in the third group (HR 0.56, 95% CI 0.34–0.92, p = 0.023). Clonal evolution occurs as disease progresses after different chemotherapy lines. Patients who acquired high-risk CA had the poorest prognosis. Our findings highlight the importance of performing FISH analysis both at diagnosis and at relapse.
- Published
- 2020