Top

17-04-2024 | Mantle Cell Lymphoma | Research

Monocyte-to-platelets ratio (MPR) at diagnosis is associated with inferior progression-free survival in patients with mantle cell lymphoma: a multi-center real-life survey

Authors: Andrea Duminuco, Alessandra Romano, Isacco Ferrarini, Gabriella Santuccio, Annalisa Chiarenza, Amalia Figuera, Laura Anastasia Caruso, Giovanna Motta, Giuseppe Alberto Palumbo, Carlo Mogno, Alessia Moioli, Francesco Di Raimondo, Carlo Visco

Published in: Annals of Hematology

Abstract

Mantle cell lymphoma (MCL) pathogenesis is strongly related to the role of the tumor immune microenvironment (TIME) in which MCL cells proliferate. TIME cells can produce growth signals influencing MCL cells’ survival and exert an antitumoral immune response suppression. The activity of TIME cells might be mirrored by some ratios of peripheral blood cell subpopulations, such as the monocyte-to-platelet ratio (MPR). We reviewed the clinical features of 165 consecutive MCL patients newly diagnosed and not eligible for autologous stem cell transplantation (both for age or comorbidities) who accessed two Italian Centers between 2006 and 2020. MPR was calculated using data obtained from the complete blood cell count at diagnosis before any cytotoxic treatment and correlated with PFS. Univariate analysis showed that MPR ≥ 3 was associated with inferior PFS (p = 0.02). Multivariate analysis confirmed that MPR ≥ 3, LDH > 2.5 ULN, and bone marrow involvement were significant independent variables in predicting PFS. For these reasons, MPR ≥ 3 seems the most promising prognostic factor in patients with MCL, and it could be considered a variable in new predictive models.

Available only for authorised users

Navarro A, Beà S, Jares P, Campo E (2020) Molecular pathogenesis of Mantle Cell Lymphoma. Hematol Oncol Clin North Am 34(5):795CrossRefPubMedPubMedCentral

Silkenstedt E, Linton K, Dreyling M Mantle cell lymphoma - advances in molecular biology, prognostication and treatment approaches. Br J Haematol [Internet]. 2021 Oct 1 [cited 2022 Jun 24];195(2):162–73. https://pubmed.ncbi.nlm.nih.gov/33783838/

Hoster E, Klapper W, Hermine O, Kluin-Nelemans HC, Walewski J, van Hoof A et al Confirmation of the mantle-cell lymphoma International Prognostic Index in randomized trials of the European Mantle-Cell Lymphoma Network. J Clin Oncol [Internet]. 2014 May 1 [cited 2022 Jun 24];32(13):1338–46. https://pubmed.ncbi.nlm.nih.gov/24687837/

Hoster E, Dreyling M, Klapper W, Gisselbrecht C, van Hoof A, Kluin-Nelemans HC et al A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood [Internet]. 2008 Jan 15 [cited 2022 Jun 24];111(2):558–65. https://pubmed.ncbi.nlm.nih.gov/17962512/

Dreyling M, Campo E, Hermine O, Jerkeman M, le Gouill S, Rule S et al (2017) Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol [Internet]. [cited 2022 Jun 24];28(suppl_4):iv62–71. https://pubmed.ncbi.nlm.nih.gov/28881919/

Burger JA, Gribben JG (2014) The microenvironment in chronic lymphocytic leukemia (CLL) and other B cell malignancies: insight into disease biology and new targeted therapies. Semin Cancer Biol [Internet]. [cited 2022 Nov 14];24:71–81. https://pubmed.ncbi.nlm.nih.gov/24018164/

Chiron D, Bellanger C, Papin A, Tessoulin B, Dousset C, Maiga S et al (2016) Rational targeted therapies to overcome microenvironment-dependent expansion of mantle cell lymphoma. Blood [Internet]. Dec 15 [cited 2022 Nov 14];128(24):2808–18. https://pubmed.ncbi.nlm.nih.gov/27697772/

Saba NS, Liu D, Herman SEM, Underbayev C, Tian X, Behrend D et al Pathogenic role of B-cell receptor signaling and canonical NF-κB activation in mantle cell lymphoma. Blood [Internet]. 2016 Jul 7 [cited 2022 Nov 14];128(1):82. Available from: /pmc/articles/PMC4937360/

Duminuco A, Nardo A, Orofino A, Giunta G, Conticello C, Del Fabro V et al Efficacy and safety of tixagevimab-cilgavimab versus SARS-CoV-2 breakthrough infection in the hematological conditions. Cancer [Internet]. 2024 Jan 1 [cited 2024 Jan 13];130(1). https://pubmed.ncbi.nlm.nih.gov/37658645/

10.

Duminuco A, Romano A, Leotta D, La Spina E, Cambria D, Bulla A et al (2023) Clinical outcome of SARS-CoV-2 infections occurring in multiple myeloma patients after vaccination and prophylaxis with tixagevimab/cilgavimab. Front Oncol [Internet]. Mar 29 [cited 2023 Mar 29];13:1357. https://www.frontiersin.org/articles/https://doi.org/10.3389/fonc.2023.1157610/full

11.

Saleh K, Cheminant M, Chiron D, Burroni B, Ribrag V, Sarkozy C (2072) Tumor Microenvironment and Immunotherapy-Based Approaches in Mantle Cell Lymphoma. Cancers 2022, Vol 14, Page 3229 [Internet]. 2022 Jun 30 [cited 2022 Dec 11];14(13):3229. https://www.mdpi.com/-6694/14/13/3229/htm

12.

Papin A, le Gouill S, Chiron D Rationale for targeting tumor cells in their microenvironment for mantle cell lymphoma treatment. Leuk Lymphoma [Internet]. 2018 May 4 [cited 2022 Nov 14];59(5):1064–72. https://pubmed.ncbi.nlm.nih.gov/28758825/

13.

Romano A, Parrinello NL, Vetro C, Forte S, Chiarenza A, Figuera A et al Circulating myeloid-derived suppressor cells correlate with clinical outcome in Hodgkin Lymphoma patients treated up-front with a risk-adapted strategy. Br J Haematol [Internet]. 2015 Mar 1 [cited 2024 Jan 13];168(5):689–700. https://pubmed.ncbi.nlm.nih.gov/25376846/

14.

Giallongo S, Duminuco A, Dulcamare I, Zuppelli T, La Spina E, Scandura G et al Engagement of Mesenchymal Stromal Cells in the Remodeling of the Bone Marrow Microenvironment in Hematological Cancers. Biomolecules [Internet]. 2023 Dec 1 [cited 2024 Jan 13];13(12). https://pubmed.ncbi.nlm.nih.gov/38136573/

15.

Song M, Graubard BI, Rabkin CS, Engels EA Neutrophil-to-lymphocyte ratio and mortality in the United States general population. Scientific Reports 2021 11:1 [Internet]. 2021 Jan 11 [cited 2022 Dec 11];11(1):1–9. https://www.nature.com/articles/s41598-020-79431-7

16.

Chan JCY, Chan DL, Diakos CI, Engel A, Pavlakis N, Gill A et al The lymphocyte-to-monocyte ratio is a superior predictor of overall survival in comparison to established biomarkers of resectable colorectal cancer. Ann Surg [Internet]. 2017 Mar 1 [cited 2022 Dec 11];265(3):539–46. https://journals.lww.com/annalsofsurgery/Fulltext/2017/03000/The_Lymphocyte_to_Monocyte_Ratio_is_a_Superior.17.aspx

17.

Pan YC, Jia ZF, Cao DH, Wu YH, Jiang J, Wen SM et al Preoperative lymphocyte-to-monocyte ratio (LMR) could independently predict overall survival of resectable gastric cancer patients. Medicine (United States) [Internet]. 2018 Dec 1 [cited 2022 Dec 11];97(52). https://journals.lww.com/md-journal/Fulltext/2018/12280/Preoperative_lymphocyte_to_monocyte_ratio__LMR_.76.aspx

18.

Djordjevic D, Rondovic G, Surbatovic M, Stanojevic I, Udovicic I, Andjelic T et al (2018) Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Mean Platelet Volume-to-Platelet Count Ratio as Biomarkers in Critically Ill and Injured Patients: Which Ratio to Choose to Predict Outcome and Nature of Bacteremia? Mediators Inflamm [Internet]. [cited 2022 Dec 11];2018. https://pubmed.ncbi.nlm.nih.gov/30116146/

19.

BG S, Gosavi S, Rao AA, Shastry S, Raj SC, Sharma A et al Neutrophil-to-Lymphocyte, Lymphocyte-to-Monocyte, and Platelet-to-Lymphocyte Ratios: Prognostic Significance in COVID-19. Cureus [Internet]. 2021 Jan 11 [cited 2022 Dec 11];13(1). https://www.cureus.com/articles/48272-neutrophil-to-lymphocyte-lymphocyte-to-monocyte-and-platelet-to-lymphocyte-ratios-prognostic-significance-in-covid-19

20.

He W, Ruan Y, Yuan C, Cheng Q, Cheng H, Zeng Y et al (2019) High neutrophil-to-platelet ratio is Associated with Hemorrhagic Transformation in patients with Acute ischemic stroke. Front Neurol 10:1310CrossRefPubMedPubMedCentral

21.

Zahorec R (2021) Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratisl Lek Listy [Internet]. [cited 2022 Dec 11];122(7):474–88. https://pubmed.ncbi.nlm.nih.gov/34161115/

22.

Di Raimondo C, Caposiena Caro RD, Spallone D, Silvaggio D, Lombardo P, del Duca E et al Baseline neutrophil/lymphocyte ratio (NLR) and red blood cell distribution width (RDW) correlate with advanced stages in cutaneous squamous cell carcinoma. Int J Dermatol [Internet]. 2022 Feb 1 [cited 2022 Dec 11];61(2):175–9. https://pubmed.ncbi.nlm.nih.gov/34212366/

23.

Mano Y, Shirabe K, Yamashita YI, Harimoto N, Tsujita E, Takeishi K et al (2013) Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival after hepatectomy for hepatocellular carcinoma: a retrospective analysis. Ann Surg [Internet]. Aug [cited 2022 Dec 11];258(2):301–5. https://pubmed.ncbi.nlm.nih.gov/23774313/

24.

Santoni M, de Giorgi U, Iacovelli R, Conti A, Burattini L, Rossi L et al Pre-treatment neutrophil-to-lymphocyte ratio may be associated with the outcome in patients treated with everolimus for metastatic renal cell carcinoma. Br J Cancer [Internet]. 2013 Oct 10 [cited 2022 Dec 11];109(7):1755. Available from: /pmc/articles/PMC3790174/

25.

Romano A, Parrinello NL, Consoli ML, Marchionni L, Forte S, Conticello C et al Neutrophil to lymphocyte ratio (NLR) improves the risk assessment of ISS staging in newly diagnosed MM patients treated upfront with novel agents. Ann Hematol [Internet]. 2015 Nov 22 [cited 2022 Dec 11];94(11):1875. Available from: /pmc/articles/PMC4695982/

26.

Porrata LF, Ristow K, Habermann T, Inwards DJ, Micallef IN, Markovic SN Predicting survival for diffuse large B-cell lymphoma patients using baseline neutrophil/lymphocyte ratio. Am J Hematol [Internet]. 2010 Nov [cited 2022 Dec 11];85(11):896–9. https://pubmed.ncbi.nlm.nih.gov/20842639/

27.

Lucijanic M, Cicic D, Stoos-Veic T, Pejsa V, Lucijanic J, Dzankic AF et al Elevated Neutrophil-to-Lymphocyte-ratio and Platelet-to-Lymphocyte Ratio in Myelofibrosis: Inflammatory Biomarkers or Representatives of Myeloproliferation Itself? Anticancer Res [Internet]. 2018 May 1 [cited 2022 Dec 11];38(5):3157–63. https://pubmed.ncbi.nlm.nih.gov/29715157/

28.

Romano A, Parrinello NL, Vetro C, Chiarenza A, Cerchione C, Ippolito M et al Prognostic meaning of neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ration (LMR) in newly diagnosed Hodgkin lymphoma patients treated upfront with a PET-2 based strategy. Ann Hematol [Internet]. 2018 Jun 1 [cited 2022 Jun 24];97(6):1009–18. https://pubmed.ncbi.nlm.nih.gov/29442162/

29.

Rodrigues JM, Nikkarinen A, Hollander P, Weibull CE, Räty R, Kolstad A et al (2021) Infiltration of CD163-, PD-L1- and FoxP3-positive cells adversely affects outcome in patients with mantle cell lymphoma independent of established risk factors. Br J Haematol [Internet]. May 1 [cited 2022 Dec 11];193(3):520–31. https://onlinelibrary.wiley.com/doi/full/https://doi.org/10.1111/bjh.17366

30.

Kamoshida G, Matsuda A, Sekine W, Mizuno H, Oku T, Itoh S et al (2012) Monocyte differentiation induced by co-culture with tumor cells involves RGD-dependent cell adhesion to extracellular matrix. Cancer Lett [Internet]. Feb 28 [cited 2022 Dec 18];315(2):145–52. https://pubmed.ncbi.nlm.nih.gov/22104730/

31.

Papin A, Tessoulin B, Bellanger C, Moreau A, le Bris Y, Maisonneuve H et al (2019) CSF1R and BTK inhibitions as novel strategies to disrupt the dialog between mantle cell lymphoma and macrophages. Leukemia [Internet]. Oct 1 [cited 2022 Dec 18];33(10):2442–53. https://pubmed.ncbi.nlm.nih.gov/30940906/

32.

Stoiber D, Assinger A (2020) Platelet-Leukocyte Interplay in Cancer Development and Progression. Cells [Internet]. Apr 1 [cited 2022 Dec 11];9(4). Available from: /pmc/articles/PMC7226828/

33.

Gabrilovich DI (2017) Myeloid-Derived Suppressor Cells. Cancer Immunol Res [Internet]. Jan 1 [cited 2022 Jun 24];5(1):3–8. https://pubmed.ncbi.nlm.nih.gov/28052991/

34.

Honigberg LA, Smith AM, Sirisawad M, Verner E, Loury D, Chang B, S A [Internet] The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U. 2010 Jul 20 [cited 2022 Jun 24];107(29):13075–80. https://pubmed.ncbi.nlm.nih.gov/20615965/

35.

Gao F, Hu J, Zhang J, Xu Y Prognostic Value of Peripheral Blood Lymphocyte/monocyte Ratio in Lymphoma. J Cancer [Internet]. 2021 [cited 2024 Mar 3];12(12):3407. Available from: /pmc/articles/PMC8120176/

36.

Stefaniuk P, Szymczyk A, Podhorecka M (2020) The Neutrophil to Lymphocyte and Lymphocyte to Monocyte Ratios as New Prognostic Factors in Hematological Malignancies – A Narrative Review. Cancer Manag Res [Internet]. [cited 2024 Mar 3];12:2961. Available from: /pmc/articles/PMC7196794/

37.

Le K, Sun J, Khawaja H, Shibata M, Maggirwar SB, Smith MR et al (2021) Mantle cell lymphoma polarizes tumor-associated macrophages into M2-like macrophages, which in turn promote tumorigenesis. Blood Adv [Internet]. Jul 27 [cited 2024 Mar 3];5(14):2863–78. https://pubmed.ncbi.nlm.nih.gov/34297045/

38.

Palumbo GA, Parrinello NL, Giallongo C, D’amico E, Zanghì A, Puglisi F et al Monocytic Myeloid Derived Suppressor Cells in Hematological Malignancies. Int J Mol Sci [Internet]. 2019 Nov 1 [cited 2024 Mar 3];20(21). Available from: /pmc/articles/PMC6862591/

39.

Pham LV, Vang MT, Tamayo AT, Lu G, Challagundla P, Jorgensen JL et al Involvement of tumor-associated macrophage activation in vitro during development of a novel mantle cell lymphoma cell line, PF-1, derived from a typical patient with relapsed disease. Leuk Lymphoma [Internet]. 2015 Jan 1 [cited 2024 Mar 3];56(1):186–93. https://pubmed.ncbi.nlm.nih.gov/24611650/

40.

Araujo-Ayala F, Dobaño-López C, Valero JG, Nadeu F, Gava F, Faria C et al A novel patient-derived 3D model recapitulates mantle cell lymphoma lymph node signaling, immune profile and in vivo ibrutinib responses. Leukemia [Internet]. 2023 Jun 1 [cited 2024 Mar 3];37(6):1311–23. https://pubmed.ncbi.nlm.nih.gov/37031299/

41.

Koh YW, Shin SJ, Park C, Yoon DH, Suh C, Huh J Absolute monocyte count predicts overall survival in mantle cell lymphomas: correlation with tumour-associated macrophages. Hematol Oncol [Internet]. 2014 Dec 1 [cited 2024 Mar 3];32(4):178–86. https://pubmed.ncbi.nlm.nih.gov/24910369/

42.

von Aprile K, Conconi A, de Campos CP, Franceschetti S, Bertoni F, Margiotta Casaluci G et al (2013) Prognostic impact of monocyte count at presentation in mantle cell lymphoma. Br J Haematol [Internet]. Aug [cited 2024 Mar 3];162(4):465–73. https://pubmed.ncbi.nlm.nih.gov/23808798/

43.

Locati M, Curtale G, Mantovani A, Diversity Mechanisms, and Significance of Macrophage Plasticity. Annu Rev Pathol [Internet]. 2020 Jan 24 [cited 2024 Mar 3];15:123–47. https://pubmed.ncbi.nlm.nih.gov/31530089/

44.

Ugel S, Canegrave S, De Sanctis F, Bronte V Monocytes in the Tumor Microenvironment. Annu Rev Pathol [Internet]. 2021 Jan 24 [cited 2024 Mar 3];16:93–122. https://pubmed.ncbi.nlm.nih.gov/33497262/

Title: Monocyte-to-platelets ratio (MPR) at diagnosis is associated with inferior progression-free survival in patients with mantle cell lymphoma: a multi-center real-life survey
Authors: Andrea Duminuco
Alessandra Romano
Isacco Ferrarini
Gabriella Santuccio
Annalisa Chiarenza
Amalia Figuera
Laura Anastasia Caruso
Giovanna Motta
Giuseppe Alberto Palumbo
Carlo Mogno
Alessia Moioli
Francesco Di Raimondo
Carlo Visco
Publication date: 17-04-2024
Publisher: Springer Berlin Heidelberg
Keyword: Mantle Cell Lymphoma
Published in: Annals of Hematology
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-024-05752-6

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials