scholarly journals High Counts of CD68+ and CD163+ Macrophages in Mantle Cell Lymphoma Are Associated With Inferior Prognosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Philippa Li ◽  
Ji Yuan ◽  
Fahad Shabbir Ahmed ◽  
Austin McHenry ◽  
Kai Fu ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Response To Therapy ◽  
Rank Test ◽  
Prognostic Impact ◽  
Optimal Separation ◽  
Automated Method ◽  
Mantle Cell ◽  
Quantitative Immunofluorescence ◽  
Checkpoint Molecule

BackgroundLymphoma-associated macrophages (LAMs) are key components in the lymphoma microenvironment, which may impact disease progression and response to therapy. There are two major subtypes of LAMs, CD68+ M1 and CD163+ M2. M2 LAMs can be transformed from M1 LAMs, particularly in certain diffuse large B-cell lymphomas (DLBCL). While mantle cell lymphoma (MCL) is well-known to contain frequent epithelioid macrophages, LAM characterization within MCL has not been fully described. Herein we evaluate the immunophenotypic subclassification, the expression of immune checkpoint molecule PD-L1, and the prognostic impact of LAMs in MCL.Materials and MethodsA total of 82 MCL cases were collected and a tissue microarray block was constructed. Immunohistochemical staining was performed using CD68 and CD163, and the positive cells were recorded manually in four representative 400× fields for each case. Multiplexed quantitative immunofluorescence assays were carried out to determine PD-L1 expression on CD68+ M1 LAMs and CD163+ M2 LAMs. In addition, we assessed Ki67 proliferation rate of MCL by an automated method using the QuPath digital imaging analysis. The cut-off points of optimal separation of overall survival (OS) were analyzed using the X-Tile software, the SPSS version 26 was used to construct survival curves, and the log-rank test was performed to calculate the p-values.ResultsMCL had a much higher count of M1 LAMs than M2 LAMs with a CD68:CD163 ratio of 3:1. Both M1 and M2 LAMs were increased in MCL cases with high Ki67 proliferation rates (>30%), in contrast to those with low Ki67 (<30%). Increased number of M1 or M2 LAMs in MCL was associated with an inferior OS. Moreover, high expression of PD-L1 on M1 LAMs had a slightly better OS than the cases with low PD-L1 expression, whereas low expression of PD-L1 on M2 LAMs had a slightly improved OS, although both were not statistically significant.ConclusionsIn contrast to DLBCL, MCL had a significantly lower rate of M1 to M2 polarization, and the high levels of M1 and M2 LAMs were associated with poor OS. Furthermore, differential PD-L1 expressions on LAMs may partially explain the different functions of tumor-suppressing or tumor-promoting of M1 and M2 LAMs, respectively.

scholarly journals Modulation of immune checkpoint molecule expression in mantle cell lymphoma

2019 ◽  
Vol 60 (10) ◽  
pp. 2498-2507 ◽  
Author(s):  
Bonnie K. Harrington ◽  
Esther Wheeler ◽  
Kasey Hornbuckle ◽  
Arwa Y. Shana’ah ◽  
Youssef Youssef ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Immune Checkpoint ◽  
Cell Lymphoma ◽  
Mantle Cell ◽  
Checkpoint Molecule

scholarly journals Concurrent TP53 and CDKN2A Gene Aberrations in Newly Diagnosed Mantle Cell Lymphoma Correlate with Chemoresistance and Call for Innovative Upfront Therapy

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2120 ◽  
Author(s):  
Diana Malarikova ◽  
Adela Berkova ◽  
Ales Obr ◽  
Petra Blahovcova ◽  
Michael Svaton ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Kinase Inhibitor ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Mantle Cell ◽  
Reliable Marker

Mantle cell lymphoma (MCL) is a subtype of B-cell lymphoma with a large number of recurrent cytogenetic/molecular aberrations. Approximately 5–10% of patients do not respond to frontline immunochemotherapy. Despite many useful prognostic indexes, a reliable marker of chemoresistance is not available. We evaluated the prognostic impact of seven recurrent gene aberrations including tumor suppressor protein P53 (TP53) and cyclin dependent kinase inhibitor 2A (CDKN2A) in the cohort of 126 newly diagnosed consecutive MCL patients with bone marrow involvement ≥5% using fluorescent in-situ hybridization (FISH) and next-generation sequencing (NGS). In contrast to TP53, no pathologic mutations of CDKN2A were detected by NGS. CDKN2A deletions were found exclusively in the context of other gene aberrations suggesting it represents a later event (after translocation t(11;14) and aberrations of TP53, or ataxia telangiectasia mutated (ATM)). Concurrent deletion of CDKN2A and aberration of TP53 (deletion and/or mutation) represented the most significant predictor of short EFS (median 3 months) and OS (median 10 months). Concurrent aberration of TP53 and CDKN2A is a new, simple, and relevant index of chemoresistance in MCL. Patients with concurrent aberration of TP53 and CDKN2A should be offered innovative anti-lymphoma therapy and upfront consolidation with allogeneic stem cell transplantation.

scholarly journals Prognostic impact of monocyte count at presentation in mantle cell lymphoma - response to Georgeet al

2013 ◽  
Vol 164 (6) ◽  
pp. 893-894
Author(s):  
Kathrin Aprile von Hohenstaufen ◽  
Annarita Conconi ◽  
Cassio Polpo de Campos ◽  
Emanuele Zucca
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Prognostic Impact ◽  
Monocyte Count ◽  
Mantle Cell

Analysis of Cytogenetic Abnormalities and Their Prognostic Impact in a Series of 145 Mantle Cell Lymphoma Cases with An Abnormal Karyotype.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1765-1765
Author(s):  
Blanca Espinet ◽  
Salaverría Itziar ◽  
Sílvia Beà ◽  
Neus Ruiz-Xivillé ◽  
Olga Balagué ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Molecular Techniques ◽  
Large Series ◽  
Proliferation Index ◽  
Prognostic Impact ◽  
Histological Subtype ◽  
Proliferative Index ◽  
Abnormal Karyotype ◽  
Mantle Cell

Abstract INTRODUCTION. Mantle cell lymphoma (MCL) is a well defined mature B-cell neoplasm, usually with an aggressive behaviour and a median survival of 3–5 years. It is characterized by the presence of t(11;14)(q13;q32), that leads to overexpression of CCND1. This translocation is detected by conventional cytogenetics (CC) in more than 65% of the cases. Nevertheless, cyclin D1 overexpression alone is not sufficient to give rise to a MCL. Several secondary genetic abnormalities with a potential role in the oncogenic process have been described using different molecular and cytogenetic techniques but no data from large series of MCL cases studied by CC have been correlated with survival and proliferation information. AIMS. 1. To correlate secondary chromosomal abnormalities, histological subtype and proliferative index with survival. 2. To describe the frequency of secondary chromosomal aberrations using CC and a large series of MCL patients. PATIENTS AND METHODS. We selected 145 MCL cases (94M/51F; mean age 65.4 yrs; mean survival 33 mo.), all of them with an abnormal karyotype. Histological subtype, proliferative index (Ki-67) and survival data were collected. All patients were studied by conventional GTG-banding cytogenetics, and FISH with a dual colour dual fusion CCND1/IGH probe was applied in those cases with an abnormal karyotype but without t(11;14) detected by CC. RESULTS. Translocation t(11;14) was detected as a single anomaly in 36% of patients, whereas 57% of cases displayed t(11;14) plus other additional aberrations and 6% of patients showed an abnormal karyotype without t(11;14) which was detected by FISH. We observed a total of 550 abnormalities (147 numerical and 403 structural), being the most frequent deletions of 1p (12%), 13q and 17p (10% each) and gains of 3q (9%). Recurrent breakpoints were identified at 1p31–p32, 1p21–p22, 17p13 and 1p36 (in eight, six, five and four cases, respectively). Blastoid variants of MCL displayed more karyotypic complexity with high number of structural alterations, higher number of 1p and 17p deletions, higher proliferation index and poor survival. CONCLUSIONS. 1. MCL cases associated with 17p losses (overall survival at 4 yrs: 15% vs 50%; P=0.01) and high proliferative index (15% vs 55%; P=0.005), generally corresponding to blastoid variants, display a worse outcome. 2. Our results confirm, by means of a routine technique as CC, previous observations made using more sophisticated molecular techniques in shorter series of patients.

Discordance Between the Prognostic Impact of MIPI and Overall Survival in a Multicenter Cohort of Patients with Mantle Cell Lymphoma

2016 ◽  
Vol 16 ◽  
pp. S115
Author(s):  
Ashley Staton ◽  
I. Greenwell ◽  
Jeffrey Switchenko ◽  
Joseph Maly ◽  
Kristie Blum ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Prognostic Impact ◽  
Multicenter Cohort ◽  
Mantle Cell

Prognostic Value of Ki-67 Index, Cytology, and Growth Pattern in Mantle-Cell Lymphoma: Results From Randomized Trials of the European Mantle Cell Lymphoma Network

2016 ◽  
Vol 34 (12) ◽  
pp. 1386-1394 ◽  
Author(s):  
Eva Hoster ◽  
Andreas Rosenwald ◽  
Françoise Berger ◽  
Heinz-Wolfram Bernd ◽  
Sylvia Hartmann ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Risk Stratification ◽  
Mantle Cell Lymphoma ◽  
Growth Pattern ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Low Grade ◽  
Prognostic Impact ◽  
Ki 67 ◽  
Mantle Cell

Purpose Mantle-cell lymphoma (MCL) is a rather aggressive B-cell malignancy whose considerable variability of individual outcome is associated with clinical characteristics (Mantle Cell Lymphoma International Prognostic Index [MIPI]). The Ki-67 index is a strong independent prognostic factor; however, the biologic MIPI (MIPI-b) distinguishes only two groups, which does not appropriately depict the clinical heterogeneity. By using the cohort from the European MCL Younger and MCL Elderly trials, we aimed to evaluate the additional prognostic impact of cytology and growth pattern and to improve risk stratification with the Ki-67 index and MIPI. Patients and Methods Diagnostic tumor biopsies were reviewed by the European Mantle Cell Lymphoma Pathology Panel to determine Ki-67 index by using published guidelines, cytology, and growth pattern. We evaluated prognostic effects for overall survival (OS) by Cox regression. For the cohort used for MIPI-b development (German Low-Grade Lymphoma Study Group [GLSG] 1996 and GLSG2000), we checked whether the equally weighted combination of Ki-67 index (dichotomized at the validated 30% cutoff) and MIPI risk groups was adequate and compared the prognostic power of this modified combination to MIPI and MIPI-b for the MCL Younger/MCL Elderly cohort. Results The Ki-67 index was assessed in 508 of 832 patients (median age, 62 years). Blastoid cytology was associated with inferior OS independently of MIPI but not independently of the Ki-67 index. Growth pattern was not independently prognostic. The modified combination of the Ki-67 index and MIPI separated four groups with 5-year OS: 85%, 72%, 43%, and 17% (P < .001) and was more discriminative than MIPI and MIPI-b. Conclusion Using the Ki-67 index is superior to using cytology and growth pattern as prognostic factors in MCL. The modified combination of the Ki-67 index and MIPI showed a refined risk stratification, reflecting their strong complementary prognostic effects while integrating the most relevant prognostic factors available in clinical routine.

scholarly journals Prognostic impact of monocyte count at presentation in mantle cell lymphoma

2013 ◽  
Vol 164 (6) ◽  
pp. 890-893 ◽  
Author(s):  
Anupkumar George ◽  
Henry Miles Prince ◽  
Jeff Szer ◽  
Max Wolf ◽  
Elchanan H. Januszewicz ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Prognostic Impact ◽  
Monocyte Count ◽  
Mantle Cell

Real World Data On Primary Treatment For Mantle Cell Lymphoma 2000-2011 – a Nordic Lymphoma Group Observational Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4358-4358
Author(s):  
Anna Abrahamsson ◽  
Alexandra Albertsson Lindblad ◽  
Peter de Nully Brown ◽  
Stefanie Baumgartner Wennerholm ◽  
Lars Moller Pedersen ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Primary Treatment ◽  
Population Based ◽  
High Dose ◽  
Prognostic Impact ◽  
Significant Difference ◽  
Mantle Cell

Abstract Background There is a consensus that younger patients with mantle cell lymphoma (MCL) should receive intensive immunochemotherapy regimens including high-dose cytarabine, rituximab and high-dose chemotherapy with stem cell support, but the optimization of treatment for elderly or unfit patients, as well as patients with localized or indolent disease, remains a challenge. Methods Our study is based on data from the Swedish and Danish Lymphoma Registries from the period of 2000-2011, in Sweden supplemented by review of patients´ records. The Lymphoma Registries comprise >95% of all diagnosed lymphoma patients in Sweden and Denmark. Results 1389 patients were diagnosed with MCL, confirmed by positive cyclin-D1 and CD5 staining, in Sweden and Denmark between 2000 and 2011. In this population based cohort, we could confirm the prognostic impact of MIPI, but in addition, male sex was associated with inferior overall survival (OS) in multivariate analysis (HR 1.4, p<0.001). Treatment with the Nordic MCL2 regimen (n=324) was associated with superior outcome compared to the majority of other regimens (3-year OS: 80%). In patients >65 years, chlorambucil (n=132) was superior to CVP (n=35) (HR 1.8, p=0.003), when adjusted for MIPI and rituximab, but there was no significant difference between CHOP (n=311) and CHOP+Cytarabine (n=84). Rituximab (HR 1.5, p<0.001) and autologous stem cell transplantation (HR 1.9, p<0.001 ) per se were both associated with prolonged OS in multivariate analysis. Forty-three (3.1%) patients with stage I-II disease received radiotherapy as primary treatment with curative intent showing an estimated 3-year OS of 93%. A small proportion, 29 patients (2.1%), were followed without treatment. Estimated 3-year OS for this group of patients was 79%. Conclusion By a population-based approach, we were able to provide novel data on prognostic factors and primary treatment of MCL, applicable to routine clinical practice. Disclosures: No relevant conflicts of interest to declare.

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