SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma – a Nordic Lymphoma Group study

TY - JOUR

T1 - SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma – a Nordic Lymphoma Group study

AU - Nordström, Lena

AU - Sernbo, Sandra

AU - Eden, Patrik

AU - Grønbaek, Kirsten

AU - Kolstad, Arne

AU - Räty, Riikka

AU - Karjalainen, Marja-Liisa

AU - Geisler, Christian

AU - Ralfkiaer, Elisabeth

AU - Sundström, Christer

AU - Laurell, Anna

AU - Delabie, Jan

AU - Ehinger, Mats

AU - Jerkeman, Mats

AU - Ek, Sara

N1 - © 2014 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

PY - 2014/7

Y1 - 2014/7

N2 - Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, where survival has been remarkably improved by use of protocols including high dose cytarabine, rituximab and autologous stem cell transplantation, such as the Nordic MCL2/3 protocols. In 2008, a MCL international prognostic index (MIPI) was created to enable stratification of the clinical diverse MCL patients into three risk groups. So far, use of the MIPI in clinical routine has been limited, as it has been shown that it inadequately separates low and intermediate risk group patients. To improve outcome and minimize treatment-related morbidity, additional parameters need to be evaluated to enable risk-adapted treatment selection. We have investigated the individual prognostic role of the MIPI and molecular markers including SOX11, TP53 (p53), MKI67 (Ki-67) and CCND1 (cyclin D1). Furthermore, we explored the possibility of creating an improved prognostic tool by combining the MIPI with information on molecular markers. SOX11 was shown to significantly add prognostic information to the MIPI, but in multivariate analysis TP53 was the only significant independent molecular marker. Based on these findings, we propose that TP53 and SOX11 should routinely be assessed and that a combined TP53/MIPI score may be used to guide treatment decisions.

AB - Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, where survival has been remarkably improved by use of protocols including high dose cytarabine, rituximab and autologous stem cell transplantation, such as the Nordic MCL2/3 protocols. In 2008, a MCL international prognostic index (MIPI) was created to enable stratification of the clinical diverse MCL patients into three risk groups. So far, use of the MIPI in clinical routine has been limited, as it has been shown that it inadequately separates low and intermediate risk group patients. To improve outcome and minimize treatment-related morbidity, additional parameters need to be evaluated to enable risk-adapted treatment selection. We have investigated the individual prognostic role of the MIPI and molecular markers including SOX11, TP53 (p53), MKI67 (Ki-67) and CCND1 (cyclin D1). Furthermore, we explored the possibility of creating an improved prognostic tool by combining the MIPI with information on molecular markers. SOX11 was shown to significantly add prognostic information to the MIPI, but in multivariate analysis TP53 was the only significant independent molecular marker. Based on these findings, we propose that TP53 and SOX11 should routinely be assessed and that a combined TP53/MIPI score may be used to guide treatment decisions.

KW - Adolescent

KW - Adult

KW - Aged

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Child

KW - Cohort Studies

KW - Cyclin D1

KW - Female

KW - Humans

KW - Lymphoma, Mantle-Cell

KW - Male

KW - Neoplasm Proteins

KW - Neoplasm Staging

KW - Prognosis

KW - SOXC Transcription Factors

KW - Severity of Illness Index

KW - Survival Analysis

KW - Treatment Outcome

KW - Tumor Markers, Biological

KW - Tumor Suppressor Protein p53

U2 - 10.1111/bjh.12854

DO - 10.1111/bjh.12854

M3 - Journal article

C2 - 24684350

SN - 0963-1860

VL - 166

SP - 98

EP - 108

JO - British Journal of Haematology, Supplement

JF - British Journal of Haematology, Supplement

IS - 1

ER -