Skip to main content
SpringerLink
Log in

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

  • Research
  • Published:
Annals of Hematology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

No datasets were generated or analysed during the current study.

References

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

    Article  PubMed  PubMed Central  Google Scholar 

  2. 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/

  3. 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/

  4. 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/

  5. 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/

  6. 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/

  7. 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/

  8. 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/

  9. 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 10:1310

    Article  PubMed  PubMed Central  Google Scholar 

  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/

Download references

Funding

No foundation to declare.

Author information

Authors and Affiliations

  1. Hematology with BMT Unit, A.O.U. “G. Rodolico-San Marco”, Catania, Italy

    Andrea Duminuco, Alessandra Romano, Gabriella Santuccio, Annalisa Chiarenza, Amalia Figuera, Laura Anastasia Caruso, Giovanna Motta, Giuseppe Alberto Palumbo & Francesco Di Raimondo

  2. Dipartimento di Specialità Medico-Chirurgiche, CHIRMED, University of Catania, Catania, Italy

    Alessandra Romano & Francesco Di Raimondo

  3. Dipartimento di Scienze Mediche Chirurgiche e Tecnologie Avanzate “G.F. Ingrassia”, University of Catania, Catania, Italy

    Isacco Ferrarini & Giuseppe Alberto Palumbo

  4. Department of Engineering for Innovation Medicine, Section of Hematology, AOUI VR, University of Verona, Verona, Italy

    Carlo Mogno, Alessia Moioli & Carlo Visco

  5. Hematology with BMT Unit – A.O.U. Policlinico “G. Rodolico-San Marco”, Via Santa Sofia, 78, Catania, 95123, Italy

    Andrea Duminuco

Authors
  1. Andrea Duminuco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alessandra Romano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Isacco Ferrarini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gabriella Santuccio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Annalisa Chiarenza
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Amalia Figuera
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Laura Anastasia Caruso
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Giovanna Motta
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Giuseppe Alberto Palumbo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Carlo Mogno
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Alessia Moioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Francesco Di Raimondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Carlo Visco
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.D., A.R., F.D.R., and C.V. designed the research; G.S., A.D., A.R., A.C., M.A., A.F., L.A.C., I.F., C.M. G.A.P., G.M. collected the data; A.D. and A.R. analyzed the data and wrote the paper, F.D.R. and C.V. reviewed the paper. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Andrea Duminuco.

Ethics declarations

Competing interests

The authors declare no competing interests.

Disclosure of conflicts of interest

The authors have no competing interests.

Human ethics and consent to participate declarations

All patients or legal guardians provided written informed consent. The study was approved by Ethic Committee Catania 1 (54/2022/PO, 31/03/2022).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The authors Andrea Duminuco and Alessandra Romano contributed equally as co-first.

The authors Francesco Di Raimondo and Carlo Visco contributed equally as co-last.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Duminuco, A., Romano, A., Ferrarini, I. et al. 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. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05752-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00277-024-05752-6

Keywords

Search

Navigation