title: Additional-structural-chromosomal aberrations are associated with inferior clinical outcome in patients with hyperdiploid multiple myeloma: a single-institution experience.
abstract: Multiple myeloma is cytogenetically heterogeneous and a hyperdiploid karyotype is considered currently to have standard risk. In this study, we investigated the clinical impact of additional-structural-chromosomal aberrations assessed by chromosome analysis in 284 patients with a hyperdiploid karyotype that were subdivided into four groups based on the complexity of additional-structural-chromosomal aberrations: group 1, no additional-structural-chromosomal aberrations (n=35); group 2, one additional-structural-chromosomal aberration (n=46); group 3, two additional-structural-chromosomal aberrations (n=39); group 4, ≥three additional-structural-chromosomal aberrations (n=164). Clinicopathological data among these groups showed no differences, except patients in group 1 had higher hemoglobin (P=0.031) and albumin (P=0.045) levels. The median follow-up was 55 months (range, 3-221). The median overall survival of patients in groups 1-4 was negatively correlated with the number of the additional-structural-chromosomal aberrations: 98, 76, 61, and 48 months, respectively (P<0.0001). In group 4, CKS1B gain, RB1, or TP53 deletions had no additional impact on overall survival; however, trisomy 3 or 15 conferred a much better overall survival, and monosomy 13 and 14 predicted a worse outcome. In addition, the overall survival of patients in groups 3 and 4 was similar to a subset of high-risk multiple myeloma cases (n=21) (P=0.387). About 192 (67.6%) patients who received stem cell transplantation did not show improved overall survival compared with non-stem cell transplantation patients (n=92; P=0.142) overall; however, they did show significantly improved overall survival in patients with refractory disease in group 4 (P=0.0084). Multivariate analysis showed that two or more additional-structural-chromosomal aberrations (P<0.0001), stages (P=0.02 and P=0.002) and relapsed disease (P=0.009) negatively impacted the overall survival. We conclude that hyperdiploid karyotypes in multiple myeloma are associated with additional-structural-chromosomal aberrations and a greater number of additional-structural-chromosomal aberrations predicts poorer clinical outcome. A hyperdiploid karyotype with ≥2 additional-structural-chromosomal aberrations at chromosomal level should be considered an independent high-risk factor.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Adrian A
authors.initials: AA
authors.lastname: Carballo-Zarate
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Oncology, Jiangsu Hospital of Traditional Chinese Medicine, Nanjing, China.
authors.forename: Lianghua
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jatin J
authors.initials: JJ
authors.lastname: Shah
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Weber
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sheeba K
authors.initials: SK
authors.lastname: Thomas
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Elisabet E
authors.initials: EE
authors.lastname: Manasanch
authors.affiliation: Department of Pathology and Laboratory Medicine, The Methodist Hospital, Houston, TX, USA.
authors.forename: Suyang
authors.initials: S
authors.lastname: Hao
authors.affiliation: Central Florida Pathology Associates, Orlando, FL, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Lin
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D042846:CDC2-CDC28 Kinases / Q000235:genetics; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics* / Q000648:ultrastructure; D004171:Diploidy; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D059785:Karyotype; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015999:Multivariate Analysis; D010641:Phenotype; D056286:Retinoblastoma Binding Proteins / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D033581:Stem Cell Transplantation; D013781:Texas; D013997:Time Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C093090:CKS1B protein, human; C000606393:RB1 protein, human; D056286:Retinoblastoma Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; D042846:CDC2-CDC28 Kinases