@article{f095cf86e02e4794aaf44e3df3763386,
title = "Complex karyotype in patients with mantle cell lymphoma predicts inferior survival and poor response to intensive induction therapy",
abstract = "BACKGROUND: Risk stratification of newly diagnosed patients with mantle cell lymphoma (MCL) primarily is based on the MCL International Prognostic Index (MIPI) and Ki-67 proliferative index. Single-center studies have reported inferior outcomes in patients with a complex karyotype (CK), but this remains an area of controversy. METHODS: The authors retrospectively reviewed 483 patients from 5 academic centers in the United States and described the effect of a CK on survival outcomes in individuals with MCL. RESULTS: A CK was found to be associated with inferior overall survival (OS) (4.5 vs 11.6 years; P<.01) and progression-free survival (PFS) (1.9 vs 4.4 years; P<.01). In patients who underwent high-intensity induction followed by autologous stem cell transplantation (ASCT) in first remission, a CK was associated with poor OS (5.1 vs 11.6 years; P =.04) and PFS (3.6 vs 7.8 years; P<.01). Among patients with a CK, high-intensity induction had no effect on OS (4.5 vs 3.8 years; P =.77) nor PFS (2.3 vs 1.5 years; P =.46). Similarly, ASCT in first remission did not improve PFS (3.5 vs 1.2 years; P =.12) nor OS (5.1 vs 4.0 years; P =.27). On multivariable analyses with Ki-67 and MIPI, only CK was found to be predictive of OS (hazard ratio [HR], 1.98; 95% confidence interval [95% CI], 1.12-3.49 [P =.02]), whereas both CK (HR, 1.91; 95% CI, 1.17-3.12 [P =.01]) and Ki-67 >30% (HR, 1.86; 95% CI, 1.06-3.28 [P =.03]) were associated with inferior PFS. Multivariable analysis did not identify any specific cytogenetic abnormalities associated with inferior survival. CONCLUSIONS: CK appears to be independently associated with inferior outcomes in patients with MCL regardless of the intensity of induction therapy and receipt of ASCT. Cytogenetics should be incorporated into the workup of a new diagnosis of MCL and novel therapeutic approaches should be investigated for patients with CK. Cancer 2018;124:2306-15.",
keywords = "chemotherapy, complex karyotype, cytogenetics, mantle cell lymphoma (MCL), prognostic markers",
author = "Greenwell, {I. Brian} and Staton, {Ashley D.} and Lee, {Michael J.} and Switchenko, {Jeffrey M.} and Saxe, {Debra F.} and Maly, {Joseph J.} and Blum, {Kristie A.} and Grover, {Natalie S.} and Mathews, {Stephanie P.} and Gordon, {Max J.} and Danilov, {Alexey V.} and Narendranath Epperla and Fenske, {Timothy S.} and Mehdi Hamadani and Park, {Steven I.} and Flowers, {Christopher R.} and Cohen, {Jonathon B.}",
note = "Funding Information: Supported in part by the Biostatistics and Bioinformatics Shared Resource of the Winship Cancer Institute of Emory University and the National Institutes of Health/National Cancer Institute under award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: I. Brian Greenwell has received a grant from the Lymphoma Research Foundation for work performed outside of the current study. Kristie A. Blum has received research funding from Mor-phoSys, Millennium, and the Ohio State University for work performed outside of the current study. Natalie S. Grover holds stock in Sangamo Therapeutics. Alexey V. Danilov has received grants from Gilead Sciences and Takeda Oncology; personal fees and nonfinancial support from Genentech; and personal fees from Juno Therapeutics, TG Therapeutics, AstraZeneca, AbbVie, and Vera-stem for work performed outside of the current study. Timothy S. Fenske has acted as a paid consultant or in an advisory role for Cel-gene, Seattle Genetics, and Pharmacyclics and has received research funding from Millennium for work performed outside of the current study. Steven I. Park has acted as a paid consultant or in an advisory role for Teva and Cornerstone Pharmaceuticals and has received research funding from Teva, Seattle Genetics, and Takeda for work performed outside of the current study. Christopher R. Flowers has acted as a paid consultant or in an advisory role for OptumRx and Seattle Genetics; has received institutional funding from Acerta Pharma, Infinity Pharmaceuticals, Onyx, and Janssen Oncology; has received institutional funding and personal fees from Gilead Sciences, Celgene, TG Therapeutics, and Genentech/ Roche; and has received institutional funding from Pharmacyclics and AbbVie for work performed outside of the current study. Jona-thon B. Cohen is a Lymphoma Research Foundation grantee and has received funding from the American Society of Hematology for work performed as part of the current study. Publisher Copyright: {\textcopyright} 2018 American Cancer Society",
year = "2018",
month = jun,
day = "1",
doi = "10.1002/cncr.31328",
language = "English (US)",
volume = "124",
pages = "2306--2315",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "11",
}