Complex karyotype in patients with mantle cell lymphoma predicts inferior survival and poor response to intensive induction therapy

I. Brian Greenwell; Ashley D. Staton; Michael J. Lee; Jeffrey M. Switchenko; Debra F. Saxe; Joseph J. Maly; Kristie A. Blum; Natalie S. Grover; Stephanie P. Mathews; Max J. Gordon; Alexey V. Danilov; Narendranath Epperla; Timothy S. Fenske; Mehdi Hamadani; Steven I. Park; Christopher R. Flowers; Jonathon B. Cohen

doi:10.1002/cncr.31328

Complex karyotype in patients with mantle cell lymphoma predicts inferior survival and poor response to intensive induction therapy

I. Brian Greenwell, Ashley D. Staton, Michael J. Lee, Jeffrey M. Switchenko, Debra F. Saxe, Joseph J. Maly, Kristie A. Blum, Natalie S. Grover, Stephanie P. Mathews, Max J. Gordon, Alexey V. Danilov, Narendranath Epperla, Timothy S. Fenske, Mehdi Hamadani, Steven I. Park, Christopher R. Flowers, Jonathon B. Cohen

Knight Cancer Institute

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2306-2315
Number of pages	10
Journal	Cancer
Volume	124
Issue number	11
DOIs	https://doi.org/10.1002/cncr.31328
State	Published - Jun 1 2018

Keywords

chemotherapy
complex karyotype
cytogenetics
mantle cell lymphoma (MCL)
prognostic markers

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1002/cncr.31328

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Greenwell, I. B., Staton, A. D., Lee, M. J., Switchenko, J. M., Saxe, D. F., Maly, J. J., Blum, K. A., Grover, N. S., Mathews, S. P., Gordon, M. J., Danilov, A. V., Epperla, N., Fenske, T. S., Hamadani, M., Park, S. I., Flowers, C. R., & Cohen, J. B. (2018). Complex karyotype in patients with mantle cell lymphoma predicts inferior survival and poor response to intensive induction therapy. Cancer, 124(11), 2306-2315. https://doi.org/10.1002/cncr.31328

Greenwell, IB, Staton, AD, Lee, MJ, Switchenko, JM, Saxe, DF, Maly, JJ, Blum, KA, Grover, NS, Mathews, SP, Gordon, MJ, Danilov, AV, Epperla, N, Fenske, TS, Hamadani, M, Park, SI, Flowers, CR & Cohen, JB 2018, 'Complex karyotype in patients with mantle cell lymphoma predicts inferior survival and poor response to intensive induction therapy', Cancer, vol. 124, no. 11, pp. 2306-2315. https://doi.org/10.1002/cncr.31328

@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. 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",

}

TY - JOUR

T1 - Complex karyotype in patients with mantle cell lymphoma predicts inferior survival and poor response to intensive induction therapy

AU - Greenwell, I. Brian

AU - Staton, Ashley D.

AU - Lee, Michael J.

AU - Switchenko, Jeffrey M.

AU - Saxe, Debra F.

AU - Maly, Joseph J.

AU - Blum, Kristie A.

AU - Grover, Natalie S.

AU - Mathews, Stephanie P.

AU - Gordon, Max J.

AU - Danilov, Alexey V.

AU - Epperla, Narendranath

AU - Fenske, Timothy S.

AU - Hamadani, Mehdi

AU - Park, Steven I.

AU - Flowers, Christopher R.

AU - Cohen, Jonathon B.

N1 - 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. Publisher Copyright: © 2018 American Cancer Society

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

KW - chemotherapy

KW - complex karyotype

KW - cytogenetics

KW - mantle cell lymphoma (MCL)

KW - prognostic markers

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U2 - 10.1002/cncr.31328

DO - 10.1002/cncr.31328

M3 - Article

C2 - 29579328

AN - SCOPUS:85044426982

VL - 124

SP - 2306

EP - 2315

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 11

ER -

Complex karyotype in patients with mantle cell lymphoma predicts inferior survival and poor response to intensive induction therapy

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