title: Outcome of Patients with Multiple Myeloma and CKS1B Gene Amplification after Autologous Hematopoietic Stem Cell Transplantation.
abstract: The gain/amplification of the CKS1B gene on chromosome 1q21 region is associated with a poor outcome in patients with multiple myeloma (MM). However, there are limited data on the outcome of patients with CKS1B amplification after a single high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT). We retrospectively evaluated the outcome of patients with CKS1B amplification who received an auto-HCT between June 2012 and July 2014 at our institution. We identified 58 patients with MM and CKS1B gene amplification detected by fluorescent in situ hybridization (FISH). We compared their outcomes with a propensity score-matched control group of 58 patients without CKS1B amplification who were treated at approximately the same time. The primary objective was to compare the progression-free (PFS) and overall survival (OS) between the CKS1B and the control groups. Stratified log-rank test with the matched pairs as strata and double robust estimation under the Cox model were used to assess the effect of CKS1B gene amplification on PFS or OS in the matched cohort. Patients in the CKS1B and control groups were well matched for age, gender, disease status, year of auto-HCT, response to pretransplantation therapy, and baseline hemoglobin level. In both groups, 57% patients were in first remission and 43% had relapsed disease at auto-HCT. Twenty-seven (47%) patients with CKS1B amplification had concurrent monosomy 13 or 13q deletion; 6 (10%) by conventional cytogenetics only, 16 (28%) by FISH only, and 5 (9%) by both. Median follow-up after auto-HCT was 25.4 months. The median PFS of the CKS1B and the control groups were 15.0 months and 33.0 months (P = .002), respectively. The median OS have not been reached yet. The 2-year OS rates in the CKS1B and the control groups were 62% and 91% (P = .02), respectively. In conclusion, Patients with CKS1B amplification are more likely to have additional high-risk cytogenetic abnormalities and a shorter PFS and OS after an auto-HCT.
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas; Institute of Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Bock
authors.affiliation: Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gary
authors.initials: G
authors.lastname: Lu
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Samer A
authors.initials: SA
authors.lastname: Srour
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sameh
authors.initials: S
authors.lastname: Gaballa
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Heather Y
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Veerabhadran
authors.initials: V
authors.lastname: Baladandayuthapani
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Medhavi
authors.initials: M
authors.lastname: Honhar
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Stich
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nina Das
authors.initials: ND
authors.lastname: Shah
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Qaiser
authors.initials: Q
authors.lastname: Bashir
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Krina
authors.initials: K
authors.lastname: Patel
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Uday
authors.initials: U
authors.lastname: Popat
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Chitra
authors.initials: C
authors.lastname: Hosing
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Martin
authors.initials: M
authors.lastname: Korbling
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ruby
authors.initials: R
authors.lastname: Delgado
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rondon
authors.affiliation: Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jatin J
authors.initials: JJ
authors.lastname: Shah
authors.affiliation: Department of Lymphoma/Myeloma, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sheeba K
authors.initials: SK
authors.lastname: Thomas
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Elisabet E
authors.initials: EE
authors.lastname: Manasanch
authors.affiliation: Institute of Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Berend
authors.initials: B
authors.lastname: Isermann
authors.affiliation: Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: mqazilba@mdanderson.org.
authors.forename: Muzaffar H
authors.initials: MH
authors.lastname: Qazilbash
mesh_terms: D000328:Adult; D000368:Aged; D042846:CDC2-CDC28 Kinases / Q000235:genetics*; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D012189:Retrospective Studies; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: C093090:CKS1B protein, human; D042846:CDC2-CDC28 Kinases
keywords: 1q21; CKS1B; Multiple myeloma; Stem cell transplantation