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Li N, An N, Ma S, Cao J, Zhu F, Qi K, Yan Z, Cheng H, Sang W, Chen W, Li D, Li Z, Xu K, Wang Y. Lymphocyte/monocyte to lactate dehydrogenase ratio prior to lymphodepletion impact the outcomes of patients with diffused large B cell lymphoma undergoing CAR-T cell therapy. Cancer Immunol Immunother 2025; 74:148. [PMID: 40088299 PMCID: PMC11910468 DOI: 10.1007/s00262-025-03987-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 02/17/2025] [Indexed: 03/17/2025]
Abstract
Factors associated with outcomes of chimeric antigen receptor (CAR)-T cell therapy in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have not been fully elucidated. We explored the impact of the prelymphodepletion (pre-LD) lymphocyte to monocyte ratio (LMR) and its ratio to lactate dehydrogenase (LDH) (LMR/LDH) on the efficacy and prognosis of 60 patients with R/R DLBCL undergoing CAR-T cell therapy. The optimal cutoff values for pre-LD LMR and LMR/LDH were 3.583 and 0.0103, respectively. The overall response rate (ORR)s were higher in patients with high pre-LD LMR or LMR/LDH than those with low pre-LD LMR or LMR/LDH (ORR, 100% vs. 65.79%, P = 0.006 and 96.15% vs. 38.24%, P < 0.0001, respectively). Pre-LD LMR/LDH was an independent factor associated with ORR (P = 0.010, odds ratio = 18.757; 95% confidence interval [CI] 2.046-171.975) by multivariate logistic regression analysis. Patients with high pre-LD LMR/LDH had significantly longer progression-free survival (PFS) (median PFS, 29.73 vs. 2.47 months, P < 0.0001) and overall survival (OS) (median OS, not reached vs. 7.4 months, P = 0.0002) than those with low pre-LD LMR/LDH. Multivariate Cox regression analysis showed that pre-LD LMR/LDH and ORR were independent factors affecting PFS (P = 0.030, hazard ratio [HR] = 2.561; 95% CI 1.093-5.999 and P = 0.024, HR = 2.202; 95% CI 1.22-4.369, respectively); pre-LD LMR/LDH was an independent factor affecting OS (P = 0.029, HR = 3.331; 95% CI 1.131-9.807). In conclusion, the pre-LD LMR/LDH was an independent factor associated with ORR and an independent prognostic factor in patients with R/R DLBCL undergoing CAR-T cell therapy.
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Affiliation(s)
- Na Li
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Na An
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Sha Ma
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China
| | - Jiang Cao
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China
| | - Feng Zhu
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China
| | - Kunming Qi
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China
| | - Zhiling Yan
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China
| | - Hai Cheng
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China
| | - Wei Sang
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China
| | - Wei Chen
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China
| | - Depeng Li
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China
| | - Zhenyu Li
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China
| | - Kailin Xu
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China
| | - Ying Wang
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.
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Dabrowska-Iwanicka A, Nowakowski GS. DLBCL: who is high risk and how should treatment be optimized? Blood 2024; 144:2573-2582. [PMID: 37922443 DOI: 10.1182/blood.2023020779] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 10/24/2023] [Accepted: 10/24/2023] [Indexed: 11/05/2023] Open
Abstract
ABSTRACT Diffuse large B-cell lymphoma (DLBCL), not otherwise specified, is the most common subtype of large B-cell lymphoma, with differences in prognosis reflecting heterogeneity in the pathological, molecular, and clinical features. Current treatment standard is based on multiagent chemotherapy, including anthracycline and monoclonal anti-CD20 antibody, which leads to cure in 60% of patients. Recent years have brought new insights into lymphoma biology and have helped refine the risk groups. The results of these studies inspired the design of new clinical trials with targeted therapies and response-adapted strategies and allowed to identify groups of patients potentially benefiting from new agents. This review summarizes recent progress in identifying high-risk patients with DLBCL using clinical and biological prognostic factors assessed at diagnosis and during treatment in the front-line setting, as well as new treatment strategies with the application of targeted agents and immunotherapy, including response-adapted strategies.
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Affiliation(s)
- Anna Dabrowska-Iwanicka
- Department of Lymphoid Malignancies, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
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3
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Maurer K, Grabski IN, Houot R, Gohil SH, Miura S, Redd R, Lyu H, Lu W, Arihara Y, Budka J, McDonough M, Ansuinelli M, Reynolds C, Jacene H, Li S, Livak KJ, Ritz J, Miles B, Mattie M, Neuberg DS, Irizarry RA, Armand P, Wu CJ, Jacobson C. Baseline immune state and T-cell clonal kinetics are associated with durable response to CAR-T therapy in large B-cell lymphoma. Blood 2024; 144:2490-2502. [PMID: 39241199 PMCID: PMC11952007 DOI: 10.1182/blood.2024024381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 07/30/2024] [Accepted: 08/12/2024] [Indexed: 09/08/2024] Open
Abstract
ABSTRACT Engineered cellular therapy with CD19-targeting chimeric antigen receptor T cells (CAR-Ts) has revolutionized outcomes for patients with relapsed/refractory large B-cell lymphoma (LBCL), but the cellular and molecular features associated with response remain largely unresolved. We analyzed serial peripheral blood samples ranging from the day of apheresis (day -28/baseline) to 28 days after CAR-T infusion from 50 patients with LBCL treated with axicabtagene ciloleucel by integrating single-cell RNA and T-cell receptor sequencing, flow cytometry, and mass cytometry to characterize features associated with response to CAR-T. Pretreatment patient characteristics associated with response included the presence of B cells and increased absolute lymphocyte count to absolute monocyte count ratio (ALC/AMC). Infusion products from responders were enriched for clonally expanded, highly activated CD8+ T cells. We expanded these observations to 99 patients from the ZUMA-1 cohort and identified a subset of patients with elevated baseline B cells, 80% of whom were complete responders. We integrated B-cell proportion ≥0.5% and ALC/AMC ≥1.2 into a 2-factor predictive model and applied this model to the ZUMA-1 cohort. Estimated progression-free survival at 1 year in patients meeting 1 or both criteria was 65% vs 31% for patients meeting neither criterion. Our results suggest that patients' immunologic state at baseline affects the likelihood of response to CAR-T through both modulation of the T-cell apheresis product composition and promoting a more favorable circulating immune compartment before therapy. These baseline immunologic features, measured readily in the clinical setting before CAR-T, can be applied to predict response to therapy.
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MESH Headings
- Humans
- Immunotherapy, Adoptive/methods
- Lymphoma, Large B-Cell, Diffuse/therapy
- Lymphoma, Large B-Cell, Diffuse/immunology
- Male
- Female
- Middle Aged
- Aged
- Adult
- Receptors, Chimeric Antigen/immunology
- Biological Products/therapeutic use
- Antigens, CD19/immunology
- Receptors, Antigen, T-Cell/immunology
- Receptors, Antigen, T-Cell/genetics
- T-Lymphocytes/immunology
- Treatment Outcome
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Affiliation(s)
- Katie Maurer
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
- Harvard Medical School, Boston, MA
- Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA
| | | | - Roch Houot
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
- Department of Hematology, University Hospital of Rennes, UMR U1236, INSERM, University of Rennes, Rennes, France
| | - Satyen H. Gohil
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
- Department of Haematology, University College London, London, United Kingdom
- Department of Haematology, University College London Hospitals National Health Service Foundation Trust, London, United Kingdom
| | - Shogo Miura
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Robert Redd
- Department of Biostatistics, Harvard University, Boston, MA
| | - Haoxiang Lyu
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
- Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA
| | - Wesley Lu
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
- Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA
| | - Yohei Arihara
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | | | - Mikaela McDonough
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Michela Ansuinelli
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Carol Reynolds
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Heather Jacene
- Harvard Medical School, Boston, MA
- Department of Imaging, Dana-Farber Cancer Institute, Boston, MA
| | - Shuqiang Li
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
- Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA
- Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA
| | - Kenneth J. Livak
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
- Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA
| | - Jerome Ritz
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
- Harvard Medical School, Boston, MA
| | | | | | - Donna S. Neuberg
- Department of Data Science, Dana-Farber Cancer Institute, Boston, MA
| | - Rafael A. Irizarry
- Department of Biostatistics, Harvard University, Boston, MA
- Department of Data Science, Dana-Farber Cancer Institute, Boston, MA
| | - Philippe Armand
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
- Harvard Medical School, Boston, MA
| | - Catherine J. Wu
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
- Harvard Medical School, Boston, MA
- Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA
| | - Caron Jacobson
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
- Harvard Medical School, Boston, MA
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Lymphocyte-to-Monocyte Ratio May Serve as a Better Prognostic Indicator Than Tumor-associated Macrophages in DLBCL Treated With Rituximab. Appl Immunohistochem Mol Morphol 2020; 27:572-580. [PMID: 30106758 DOI: 10.1097/pai.0000000000000645] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
There are multiple prognostic indicators for diffuse large B-cell lymphoma (DLBCL) including the international prognostic index (IPI), and gene expression profiling (GEP) to classify the disease into germinal center B-cell and activated B-cell subtypes, the latter harboring inferior prognosis. More recently, tumor-associated macrophages (TAM) and lymphocyte-to-monocyte ratio (LMR) were found to have prognostic implications in DLBCL. However, consensus is yet to be reached in terms of the significance of each. In this study, we evaluated the prognostic value of TAM as assessed by CD163 or CD68 positivity by immunohistochemistry on tissue biopsies and LMR was calculated from peripheral blood differential, with focus on the inclusion of rituximab as a treatment modality. The number of CD68-positive cells in the tumor microenvironment did not exhibit significant prognostic value, whereas higher number of CD163-positive cells was associated with inferior overall survival in patients treated with chemotherapy alone. This effect was no longer evident in patients treated with rituximab containing chemoimmunotherapy. In contrast, the prognostic significance of LMR on survival was more persistent regardless of treatment. There was no association between LMR and the number of CD163-positive cells. Our results suggest that LMR is the more easily and widely available prognostic marker in this era of chemoimmunotherapy. Our finding supports previous literature that the effect of TAM can vary according to treatment. Interaction between rituximab and TAM warrant further scientific investigation for mechanistic insights into targeted therapeutics.
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Low Absolute Lymphocyte Counts in the Peripheral Blood Predict Inferior Survival and Improve the International Prognostic Index in Testicular Diffuse Large B-Cell Lymphoma. Cancers (Basel) 2020; 12:cancers12071967. [PMID: 32698344 PMCID: PMC7409117 DOI: 10.3390/cancers12071967] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 07/14/2020] [Accepted: 07/15/2020] [Indexed: 02/06/2023] Open
Abstract
Low absolute lymphocyte counts (ALC) and high absolute monocyte counts (AMC) are associated with poor survival in patients with diffuse large B-cell lymphoma (DLBCL). We studied the prognostic impact of the ALC and AMC in patients with testicular DLBCL (T-DLBCL). T-DLBCL patients were searched using Southern Finland University Hospital databases and the Danish lymphoma registry. The progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox proportional hazards methods. We identified 178 T-DLBCL patients, of whom 78 (44%) had a low ALC at diagnosis. The ALC did not correlate with survival in the whole cohort. However, among the patients treated with rituximab (R) containing regimen, a pre-therapeutic low ALC was associated with an increased risk of progression (HR 1.976, 95% CI 1.267–3.086, p = 0.003). Conversely, intravenous (iv) CNS directed chemotherapy translated to favorable outcome. In multivariate analyses, the advantage of an iv CNS directed chemotherapy was sustained (PFS, HR 0.364, 95% CI 0.175–0.757, p = 0.007). The benefit of R and intravenous CNS directed chemotherapy was observed only in non-lymphopenic patients. The AMC did not correlate with survival. A low ALC is an adverse prognostic factor in patients with T-DLBCL. Alternative treatment options for lymphopenic patients are needed.
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Lisanti C, Basile D, Parnofiello A, Bertoli E, Andreotti VJ, Garattini SK, Bartoletti M, Cattaneo M, Di Nardo P, Bonotto M, Casagrande M, Da Ros L, Cinausero M, Foltran L, Pella N, Buonadonna A, Aprile G, Fasola G, Puglisi F. The SENECA study: Prognostic role of serum biomarkers in older patients with metastatic colorectal cancer. J Geriatr Oncol 2020; 11:1268-1273. [PMID: 32576519 DOI: 10.1016/j.jgo.2020.06.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 03/27/2020] [Accepted: 06/03/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND Aging induces meaningful changes in the immune system and inflammation response with increase in monocyte-lymphocyte ratio (MLR) and serum lactate dehydrogenase (LDH) levels. Aim of this study was to explore the prognostic role of MLR and LDH levels in older patients (pts) with metastatic colorectal cancer (mCRC). METHODS We conducted a retrospective analysis of a consecutive cohort of 168 older (>70 years) patients with mCRC. The prognostic impact of MLR and LDH levels on overall survival (OS) was investigated through uni-and multivariate Cox regression analyses. Moreover, we categorized patients into three groups according to MLR and LDH levels (group 1: MLR-low and LDH-low; group 2: MLR-high or LDH-high; group 3: MLR-high and LDH-high). RESULTS By univariate analysis, high LDH level (HR 1.74, 95% CI 1.05-2.90) and high MLR level (HR 2.19, 95% CI 1.48-3.44) were significantly associated with a worse OS. Conversely, primary tumor resection and left-sidedness were significantly associated with a longer OS. By multivariate analysis, high LDH level (HR 2.00, 95% CI 1.13-3.55) and high MLR level (HR 2.99, 95% CI 1.68-5.33) were independent prognostic factors of worse prognosis. Compared to group 1, a shorter survival was reported for patients included in group 2 (HR 1.97, 95% CI 1.21-3.23 in univariate; HR 2.54, 95% CI 1.43-4.51 in multivariate) or in group 3 (HR 2.42, 95% CI 24-4.74, p = .010 in univariate; HR 5.59, 95% CI 2.15-14.54 in multivariate) CONCLUSIONS: High baseline levels of LDH, MLR or both are independent unfavorable prognostic factors in older patients treated with first-line chemotherapy for mCRC.
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Affiliation(s)
- Camilla Lisanti
- Department of Medicine (DAME), University of Udine, Udine, IT, Italy; Department of Medical Oncology, Unit of medical oncology and cancer prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, IT, Italy
| | - Debora Basile
- Department of Medicine (DAME), University of Udine, Udine, IT, Italy; Department of Medical Oncology, Unit of medical oncology and cancer prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, IT, Italy.
| | - Annamaria Parnofiello
- Department of Medicine (DAME), University of Udine, Udine, IT, Italy; Department of Medical Oncology, Unit of medical oncology and cancer prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, IT, Italy
| | - Elisa Bertoli
- Department of Medicine (DAME), University of Udine, Udine, IT, Italy; Department of Oncology, ASUIUD Santa Maria della Misericordia, Udine, IT, Italy
| | - Victoria Josephine Andreotti
- Department of Medicine (DAME), University of Udine, Udine, IT, Italy; Department of Oncology, ASUIUD Santa Maria della Misericordia, Udine, IT, Italy
| | - Silvio Ken Garattini
- Department of Medicine (DAME), University of Udine, Udine, IT, Italy; Department of Oncology, ASUIUD Santa Maria della Misericordia, Udine, IT, Italy
| | - Michele Bartoletti
- Department of Medicine (DAME), University of Udine, Udine, IT, Italy; Department of Medical Oncology, Unit of medical oncology and cancer prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, IT, Italy
| | - Monica Cattaneo
- Department of Medicine (DAME), University of Udine, Udine, IT, Italy; Department of Oncology, ASUIUD Santa Maria della Misericordia, Udine, IT, Italy
| | - Paola Di Nardo
- Department of Medical Oncology, Unit of medical oncology and cancer prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, IT, Italy
| | - Marta Bonotto
- Department of Oncology, ASUIUD Santa Maria della Misericordia, Udine, IT, Italy
| | | | - Lucia Da Ros
- Department of Medical Oncology, Unit of medical oncology and cancer prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, IT, Italy
| | - Marika Cinausero
- Department of Oncology, ASUIUD Santa Maria della Misericordia, Udine, IT, Italy
| | - Luisa Foltran
- Department of Medical Oncology, Unit of medical oncology and cancer prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, IT, Italy
| | - Nicoletta Pella
- Department of Oncology, ASUIUD Santa Maria della Misericordia, Udine, IT, Italy
| | - Angela Buonadonna
- Department of Medical Oncology, Unit of medical oncology and cancer prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, IT, Italy
| | - Giuseppe Aprile
- Department of Oncology, San Bortolo General Hospital, Azienda ULSS8 Berica, Vicenza, Italy
| | - Gianpiero Fasola
- Department of Oncology, ASUIUD Santa Maria della Misericordia, Udine, IT, Italy
| | - Fabio Puglisi
- Department of Medicine (DAME), University of Udine, Udine, IT, Italy; Department of Medical Oncology, Unit of medical oncology and cancer prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, IT, Italy
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Harkins RA, Chang A, Patel SP, Lee MJ, Goldstein JS, Merdan S, Flowers CR, Koff JL. Remaining challenges in predicting patient outcomes for diffuse large B-cell lymphoma. Expert Rev Hematol 2019; 12:959-973. [PMID: 31513757 PMCID: PMC6821591 DOI: 10.1080/17474086.2019.1660159] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 08/22/2019] [Indexed: 12/28/2022]
Abstract
Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and is an aggressive malignancy with heterogeneous outcomes. Diverse methods for DLBCL outcomes assessment ranging from clinical to genomic have been developed with variable predictive and prognostic success.Areas covered: The authors provide an overview of the various methods currently used to estimate prognosis in DLBCL patients. Models incorporating cell of origin, genomic features, sociodemographic factors, treatment effectiveness measures, and machine learning are described.Expert opinion: The clinical and genetic heterogeneity of DLBCL presents distinct challenges in predicting response to therapy and overall prognosis. Successful integration of predictive and prognostic tools in clinical trials and in a standard clinical workflow for DLBCL will likely require a combination of methods incorporating clinical, sociodemographic, and molecular factors with the aid of machine learning and high-dimensional data analysis.
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Affiliation(s)
- R. Andrew Harkins
- Emory University School of Medicine, Atlanta, Georgia 30322-1007, USA
| | - Andres Chang
- Winship Cancer Institute of Emory University, Atlanta, Georgia 30322-1007, USA
| | | | - Michelle J. Lee
- Emory University School of Medicine, Atlanta, Georgia 30322-1007, USA
| | | | - Selin Merdan
- Winship Cancer Institute of Emory University, Atlanta, Georgia 30322-1007, USA
- Georgia Institute of Technology, Atlanta, Georgia 30332-0002, USA
| | | | - Jean L. Koff
- Winship Cancer Institute of Emory University, Atlanta, Georgia 30322-1007, USA
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8
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Lee J, Hue SSS, Ko SQ, Tan SY, Liu X, Girard LP, Chan EHL, De Mel S, Jeyasekharan A, Chee YL, Koh LP, Poon LM. Clinical impact of the cell-of-origin classification based on immunohistochemistry criteria and Lymph2Cx of diffuse large B-Cell lymphoma patients in a South-east Asian population: a single center experience and review of the literature. Expert Rev Hematol 2019; 12:1095-1105. [PMID: 31592693 DOI: 10.1080/17474086.2019.1677152] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Background: Previous studies in Western populations, using immunohistochemistry (IHC) methods to subtype diffuse large B-cell lymphoma (DLBCL), suggest that germinal center B-cell lymphomas (GCBs) have improved outcomes. However, data in Asians have been limited and conflicting. This study aims to evaluate the prognostic impact of cell-of-origin (COO) subtyping by IHC and Lymph2Cx in South-East Asian (SEA) DLBCL patients, and to summarize the existing literature.Methods: A single-center retrospective analysis of 384 DLBCL patients diagnosed 2013-2018 who received Rituximab-based chemotherapy was performed. Hans and Lymph2Cx were used to assign COO and correlated with outcomes.Results: International Prognostic Index (IPI) score was associated with overall survival (OS) and progression-free survival (PFS). The 5-yr-OS for non-GCB versus GCB for COO by Hans was 70% versus 71% p=0.39, while 5-yr-OS for ABC versus GCB for COO by Lymph2Cx was 74% versus 92% p=0.19. The 5-yr-PFS for non-GCB versus GCB for COO by Hans was 65% versus 70% p=0.26, while 5-yr-PFS for ABC versus GCB for COO by Lymph2Cx was 64% versus 86% p=0.07.Conclusions: IPI is reaffirmed to be relevant in the rituximab era. COO by Hans has no prognostic significance, while subtyping by Lymph2Cx trends toward GCBs having better PFS and OS.
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Affiliation(s)
- Joanne Lee
- Department of Haematology-Oncology, National University Health System, Singapore, Singapore.,Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Susan Swee-Shan Hue
- Department of Pathology, National University Health System, Singapore, Singapore.,Science Technology and Research Singapore, Institute of Molecular and Cellular Biology, Singapore
| | - Stephanie Q Ko
- Department of Medicine, National University Health System, Singapore, Singapore
| | - Soo Yong Tan
- Department of Pathology, National University Health System, Singapore, Singapore.,Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Xin Liu
- Department of Haematology-Oncology, National University Health System, Singapore, Singapore
| | | | - Esther Hian Li Chan
- Department of Haematology-Oncology, National University Health System, Singapore, Singapore
| | - Sanjay De Mel
- Department of Haematology-Oncology, National University Health System, Singapore, Singapore
| | - Anand Jeyasekharan
- Department of Haematology-Oncology, National University Health System, Singapore, Singapore.,Cancer Science Institute, National University of Singapore, Singapore
| | - Yen Lin Chee
- Department of Haematology-Oncology, National University Health System, Singapore, Singapore.,Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Liang Piu Koh
- Department of Haematology-Oncology, National University Health System, Singapore, Singapore.,Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Li Mei Poon
- Department of Haematology-Oncology, National University Health System, Singapore, Singapore.,Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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Wang L, Sheng JJ, Zhao H, Su L, Liu CY, Wan SG. [The prognostic significance of lymphocyte/monocyte ratio in diffuse large B cell lymphoma]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2019; 40:436-438. [PMID: 31207713 PMCID: PMC7342244 DOI: 10.3760/cma.j.issn.0253-2727.2019.05.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- L Wang
- Xuanwu Hospital, Capital Medical University, Beijing 100053, China
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10
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Geng YD, Chen YR, Jin J, Wang XD, Zhang S, Li DJ. Prognostic Value of D-Dimer in Patients with Diffuse Large B-cell Lymphoma: A Retrospective Study. Curr Med Sci 2019; 39:222-227. [PMID: 31016514 DOI: 10.1007/s11596-019-2023-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 12/24/2018] [Indexed: 12/13/2022]
Abstract
This study evaluated the significance of serum D-Dimer for predicting survival of patients with diffuse large B-cell lymphoma (DLBCL). We analyzed the clinical data from 113 patients who were newly diagnosed with DLBCL at Tongji Hospital from January 2012 to January 2016. The results indicated that there were higher levels of D-Dimer in DLBCL patients with the following characteristics: stage III/IV, lymphocyte monocyte ratio (LMR) <2.27, lactate dehydrogenase (LDH) > upper limit of normal (ULN), albumin (ALB) < 35 g/L, and anemia. After the first chemotherapeutic regimen, D-Dimer was significantly decreased concomitantly with LDH. Cox univariate regression analysis showed that the overall survival (OS) was negatively affected by the following factors: age > 60 years, stage III/W, LDH > ULN, LMR < 2.27, anemia and D-Dimer > 0.92. Multivariate analysis showed that only LDH > ULN (P=0.038) and age > 60 years (P=0.047) were independent adverse prognostic factors. However, it was suggested that D-Dimer could be regarded as a marker of high tumor burden and a potential prognostic screening tool for patients with DLBCL, not otherwise specified (NOS).
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Affiliation(s)
- Yu-di Geng
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yi-Ren Chen
- College of Mathematics and Statistics, Shenzhen University, Shenzhen, 518060, China
| | - Jin Jin
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xiao-di Wang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Shu Zhang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Deng-Ju Li
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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11
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Peripheral Blood Lymphocyte-to-Monocyte Ratio as a Useful Prognostic Factor in Newly Diagnosed Multiple Myeloma. BIOMED RESEARCH INTERNATIONAL 2018; 2018:9434637. [PMID: 30599001 PMCID: PMC6287166 DOI: 10.1155/2018/9434637] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Revised: 11/07/2018] [Accepted: 11/12/2018] [Indexed: 11/30/2022]
Abstract
The survival of individuals with tumors may be predicted by the peripheral blood lymphocyte-to-monocyte ratio (LMR) upon diagnosis in recent studies. For patients with multiple myeloma (MM) in the era of novel agents, the prognostic significance of LMR remains unclear. In this study, the prognostic impact of LMR is evaluated by 285 patients with MM who are treated with proteasome inhibitor and/or immunomodulatory drug. LMR is a proven predictor of survival using the receiver operating characteristic curve, with 4.2 as the cutoff point. Patients with LMR ≤ 4.2 at diagnosis had poorer overall survival (OS) and progression-free survival (PFS) than those with LMR > 4.2. In addition, multivariate analysis showed that LMR less than 4.2 is an independent predictor for the OS (hazard ratio [HR]: 1.703; 95% confidence interval [CI]: 1.020–2.842; P = 0.042) and PFS (HR: 1.831; 95% CI: 1.098–3.053; P = 0.021). According to the test, the LMR at diagnosis, which functions as a simple index reflecting host systemic immunity, can predict clinical outcomes in patients with MM who are treated with new agents.
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12
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Chen X, Wu J, Zhang F, Ying L, Chen Y. Prognostic Significance of Pre-Operative Monocyte-to-Lymphocyte Ratio in Lung Cancer Patients Undergoing Radical Surgery. Lab Med 2018; 49:e29-e39. [PMID: 29361036 DOI: 10.1093/labmed/lmx069] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Background Inflammatory response is known to play a vital role in carcinogenesis and cancer progression. The prognostic relevance of monocyte-to-lymphocyte ratio (MLR), as a biomarker of inflammatory response has been demonstrated in patients with hematologic cancers. Objectives In this study, we assessed the prognostic relevance of MLR in patients with resectable lung carcinoma. Methods Clinical records of 705 lung cancer patients who underwent radical resection at our hospital between October 2006 and January 2011 were retrospectively reviewed. The optimal cutoff value of MLR as a prognostic indicator was determined on receiver operating characteristic curve analysis. Results On multivariate analysis using Cox proportional hazards regression model, MLR was an independent predictor of both overall survival (hazard ratio [HR] 1.494, 95% confidence interval [CI] 1.158-1.927, P = .002) and disease-free survival (HR 1.547, 95% CI 1.172-2.043, P = .002). Conclusions Preoperative MLR may be a simple, reliable prognostic marker for risk stratification and be used to guide treatment decision-making in lung cancer patients.
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Affiliation(s)
- Xiaoling Chen
- Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.,Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China
| | - Jinbiao Wu
- Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.,Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China
| | - Fanrong Zhang
- Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Zhejiang, China.,Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
| | - Lisha Ying
- Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Zhejiang, China.,Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
| | - Yu Chen
- Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.,Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China
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13
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Seo J, Kim WS, Kim JS, Kim SJ, Lee JH, Hong JS, Lee GW, Oh SY, Lee JH, Yoon DH, Lee WS, Kim HJ, Kwak JY, Kang HJ, Jo JC, Park Y, Lee HS, Kim HJ, Suh C. Platelet to lymphocyte ratio (PLR) retains independent prognostic significance in advanced stage marginal zone lymphoma patients treated with rituximab, cyclophosphamide, vincristine, and prednisone combination chemotherapy (R-CVP): Consortium for Improving Survival of Lymphoma trial. Blood Res 2017; 52:200-206. [PMID: 29043235 PMCID: PMC5641512 DOI: 10.5045/br.2017.52.3.200] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Revised: 05/28/2017] [Accepted: 07/07/2017] [Indexed: 12/11/2022] Open
Abstract
Background Rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP) is one of the effective chemotherapeutic regimens for patients with advanced stage marginal zone lymphoma (MZL). However, prognostic factors that affect the outcome of treatment for MZL are not well understood. Methods Between August 2006 and June 2013, patients with newly diagnosed stage III and IV MZL treated with R-CVP as a first-line therapy from 15 institutions were retrospectively analyzed. Patients' clinical and laboratory data at diagnosis were collected by review of medical records. Results A total of 80 patients were analyzed. Bone marrow involvement was observed in 30% cases. Twelve patients (15%) had nodal MZL, and 41.3% patients exhibited multiple mucosa-associated lymphoma tissue sites. Overall response rate was 91.3%, including 73.8% achieving complete response. Advanced MZL patients treated with R-CVP showed a 3-year progression-free survival (PFS) rate of 69.6%. Prognostic markers significantly affecting PFS in univariate analysis were platelet to lymphocyte ratio (PLR, <95 vs. ≥95, P=0.014), serum albumin (≤3.9 vs. >3.9 g/dL, P=0.008), and the International Prognostic Index (IPI) score (1 vs. 2–4, P=0.032). In multivariate analysis, only PLR (<95 vs. ≥95, HR 0.367, 95% CI, 0.139–0.971, P=0.043) was an independent risk factor for PFS. Conclusion PLR ≥95 at diagnosis is an independent prognostic marker for PFS in advanced stage MZL patients treated with R-CVP. This marker may aid clinicians in predicting the response to R-CVP chemotherapy in stage III and IV MZL patients.
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Affiliation(s)
- Jeongkuk Seo
- Department of Internal Medicine, Dong-A University Hospital, Busan, Korea
| | - Won Seog Kim
- Department of Medicine, Samsung Medical Center, Sunkyunkwan University School of Medicine, Seoul, Korea
| | - Jin Seok Kim
- Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Seok Jin Kim
- Department of Medicine, Samsung Medical Center, Sunkyunkwan University School of Medicine, Seoul, Korea
| | - Jae Hoon Lee
- Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Hospital, Incheon, Korea
| | - Jun Shik Hong
- Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Hospital, Incheon, Korea
| | - Gyeong-Won Lee
- Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Korea
| | - Sung Yong Oh
- Department of Internal Medicine, Dong-A University Hospital, Busan, Korea
| | - Ji-Hyun Lee
- Department of Internal Medicine, Dong-A University Hospital, Busan, Korea
| | - Dok Hyun Yoon
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Won-Sik Lee
- Department of Hemato/Oncology, Busan Paik Hospital, College of Medicine, Inje University, Busan, Korea
| | - Hyo Jung Kim
- Department of Internal Medicine, Hallym Medical Center, Hallym University College of Medicine, Anyang, Korea
| | - Jae-Yong Kwak
- Division of Hematology, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea
| | - Hye Jin Kang
- Division of Hematology/Oncology, Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Jae-Cheol Jo
- Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Yong Park
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Ho Sup Lee
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Hyo-Jin Kim
- Department of Internal Medicine, Dong-A University Hospital, Busan, Korea
| | - Cheolwon Suh
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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14
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Zhou S, Xu L, Ma Y, Tang L, Zhang Y, Shi Y, Sun L, Chen Y, Liang B, Zhou Y, Yu K, Shen J. Peripheral blood lymphocyte to monocyte ratio recovery from low levels at diagnosis after completion of first line therapy predicts good clinical outcomes in patients with diffuse large B-cell lymphoma. Oncotarget 2017; 8:19556-19565. [PMID: 28107187 PMCID: PMC5386705 DOI: 10.18632/oncotarget.14700] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Accepted: 12/27/2016] [Indexed: 12/31/2022] Open
Abstract
We retrospectively analyzed LMR at diagnosis and at completion of first-line therapy and prognosis in173 patients with DLBCL from 2005 to 2016. We found that patients with an LMR < 3.2 at diagnosis, as well as at completion of first-line therapy, had significantly lower PFS and OS rates than those with an LMR ≥ 3.2 (P<0.05). Patients with LMR that recovered from the low level at diagnosis showed superior overall survival (OS) (P=0.000) and progression-free survival (PFS) (P=0.001) compared with patients who failed to achieve a higher value at the completion of therapy. The multivariate analysis demonstrated that LMR values that did not increase upon completion of first-line therapy were an independent predictor for inferior OS (P=0.021) and PFS (P=0.046). In conclusion, LMR at diagnosis and at completion of first-line therapy is a simple biomarker to predict clinical outcomes in DLBCL. LMR recovery from low levels at diagnosis, irrespective of whether LMR reached the cutoff value, was associated with improved clinical outcomes.
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Affiliation(s)
- Shujuan Zhou
- The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China
| | - Linglong Xu
- The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China
| | - Yongyong Ma
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Liyuan Tang
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Yu Zhang
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Yifen Shi
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Lan Sun
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Yi Chen
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Bin Liang
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Yuhong Zhou
- Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China
| | - Kang Yu
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Jianping Shen
- Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China
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15
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Battella S, Cox MC, La Scaleia R, Di Napoli A, Di Landro F, Porzia A, Franchitti L, Mainiero F, Ruco L, Monarca B, Santoni A, Palmieri G. Peripheral blood T cell alterations in newly diagnosed diffuse large B cell lymphoma patients and their long-term dynamics upon rituximab-based chemoimmunotherapy. Cancer Immunol Immunother 2017; 66:1295-1306. [PMID: 28555258 PMCID: PMC11028700 DOI: 10.1007/s00262-017-2026-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Accepted: 05/24/2017] [Indexed: 12/17/2022]
Abstract
The importance of T cell-dependent immune responses in achieving long-term cure of chemoimmunotherapy-treated cancer patients is underscored by the recently described "vaccinal effect" exerted by therapeutic mAbs. In accordance, pre- and post-therapy peripheral blood lymphopenia represents a well-established negative prognostic factor in DLBCL. We analyzed the phenotypic and functional (IFNγ production, and Granzyme B (GrzB) cytotoxic granule marker expression) profile of peripheral blood T lymphocyte subsets ("conventional" CD4+ and CD8+, FOXP3+CD25bright Treg, and "innate-like" CD56+) in DLBCL patients at diagnosis, and assessed the long-term impact of R-CHOP chemoimmunotherapy, in a prospective study. At diagnosis, DLBCL patients showed lower lymphocyte counts, due to selective decrement of CD4+ T (including Treg) and B lymphocytes. While all T cell subsets transiently decreased during therapy, CD4+ T cell and Treg remained significantly lower than controls, up to 1 year after R-CHOP. Phenotypically skewed profile of CD4+ and CD8+ T cell subsets associated with higher frequencies of IFNγ+ and GrzB+ cells at diagnosis, that transiently decreased during therapy, and re-attained persistently elevated levels, till up to 1 year after therapy. Differently, the pre-therapy elevated levels of circulating monocytes, and of plasma IL-6 and IL-10 rapidly normalized upon R-CHOP. In sum, we describe a quantitatively and functionally altered status of the peripheral blood T cell compartment in DLBCL patients at diagnosis, that persists long-term after tumor eradication, and it is only transiently perturbed by R-CHOP chemoimmunotherapy. Moreover, data suggest the association of selected T cell functional features with DLBCL phenotype, and with therapy outcome.
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Affiliation(s)
- Simone Battella
- Department of Molecular Medicine, University La Sapienza, Rome, Italy
| | - M Christina Cox
- Hematology Unit, AO Sant'Andrea, University La Sapienza, Via di Grottarossa 1035/1039, 00189, Rome, Italy.
| | - Raffaella La Scaleia
- Department of Experimental Medicine, University La Sapienza, Viale Regina Elena 324, 00161, Rome, Italy
| | - Arianna Di Napoli
- Neuromed, Istituto di Ricovero e Cura a Carattere Scientifico, Pozzilli, IS, Italy
| | - Francesca Di Landro
- Hematology Unit, AO Sant'Andrea, University La Sapienza, Via di Grottarossa 1035/1039, 00189, Rome, Italy
| | - Alessandra Porzia
- Neuromed, Istituto di Ricovero e Cura a Carattere Scientifico, Pozzilli, IS, Italy
| | - Lavinia Franchitti
- Department of Experimental Medicine, University La Sapienza, Viale Regina Elena 324, 00161, Rome, Italy
| | - Fabrizio Mainiero
- Department of Experimental Medicine, University La Sapienza, Viale Regina Elena 324, 00161, Rome, Italy
| | - Luigi Ruco
- Department of Clinical and Molecular Medicine, University La Sapienza, Rome, Italy
| | - Bruno Monarca
- Department of Clinical and Molecular Medicine, University La Sapienza, Rome, Italy
| | - Angela Santoni
- Department of Molecular Medicine, University La Sapienza, Rome, Italy
- Istituto Pasteur-Fondazione Cenci Bolognetti, University La Sapienza, Rome, Italy
| | - Gabriella Palmieri
- Department of Experimental Medicine, University La Sapienza, Viale Regina Elena 324, 00161, Rome, Italy.
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16
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Chen YM, Fang YT, Lai CH, Rau KM, Huang CH, Chang HC, Chao TY, Tseng CC, Fang WF, Wang CC, Chen YC, Chung YH, Wang YH, Su MC, Liu SF, Huang KT, Chen HC, Chang YC, Chang YP, Lin MC. A Survival Scoring System for Non-Small Cell Lung Cancer Patients with De Novo Bone Metastases. PLoS One 2016; 11:e0167923. [PMID: 27930702 PMCID: PMC5145216 DOI: 10.1371/journal.pone.0167923] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2016] [Accepted: 11/22/2016] [Indexed: 01/18/2023] Open
Abstract
In the pre-tyrosine kinase inhibitors (TKIs) era, non-small cell lung cancer (NSCLC) patients with de novo bone metastases had a worse prognosis than those without. However, whether epidermal growth factor receptor (EGFR)-TKIs affect the outcomes of EGFR mutant NSCLC patients with de novo bone metastases has not been well studied thus far. We retrospectively studied the effect of EGFR mutation status and first-line EGFR-TKIs on patient outcomes and created a survival scoring system for NSCLC patients with de novo bone metastases. This retrospective study evaluated 1510 NSCLC patients diagnosed between November 2010 and March 2014. Among these patients, 234 patients had de novo bone metastases. We found that 121 of these 234 patients (51.7%) had positive EGFR mutation tests, and a positive EGFR mutation test significantly affected overall survival (OS) (EGFR mutant: 15.2 months, EGFR wild type: 6.5 months; p < 0.001). Other prognostic factors significant in the multivariable analysis for NSCLC with de novo bone metastases included Eastern Cooperative Oncology Group performance status (PS) (OS; PS 0–2: 11.2 months, PS 3–4: 4.9 months; p = 0.002), presence of extraosseous metastases (OS; with extraosseous metastases: 8.8 months, without extraosseous metastases: 14.0 months; p = 0.008), blood lymphocyte-to-monocyte ratio (LMR) (OS; LMR > 3.1: 17.1months, LMR ≤ 3.1: 6.9months; p < 0.001). A positive EGFR mutation status reversed the poor outcomes of NSCLC patients with de novo bone metastases. A simple and useful survival scoring system including the above clinical parameters was thus created for NSCLC patients with de novo bone metastases.
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Affiliation(s)
- Yu-Mu Chen
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ying-Tang Fang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hao Lai
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kun-Ming Rau
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Cheng-Hua Huang
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Huang-Chih Chang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tung-Ying Chao
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chia-Cheng Tseng
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Wen-Feng Fang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi Campus, Chiayi, Taiwan
| | - Chin-Chou Wang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi Campus, Chiayi, Taiwan
| | - Yung-Che Chen
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yu-Hsiu Chung
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Hsi Wang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Mao-Chang Su
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Shih-Feng Liu
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kuo-Tung Huang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hung-Chen Chen
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ya-Chun Chang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yu-Ping Chang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Meng-Chih Lin
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
- * E-mail:
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17
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Vassilakopoulos TP, Dimopoulou MN, Angelopoulou MK, Petevi K, Pangalis GA, Moschogiannis M, Dimou M, Boutsikas G, Kanellopoulos A, Gainaru G, Plata E, Flevari P, Koutsi K, Papageorgiou L, Telonis V, Tsaftaridis P, Sachanas S, Yiakoumis X, Tsirkinidis P, Viniou NA, Siakantaris MP, Variami E, Kyrtsonis MC, Meletis J, Panayiotidis P, Konstantopoulos K. Prognostic Implication of the Absolute Lymphocyte to Absolute Monocyte Count Ratio in Patients With Classical Hodgkin Lymphoma Treated With Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine or Equivalent Regimens. Oncologist 2016; 21:343-53. [PMID: 26921291 DOI: 10.1634/theoncologist.2015-0251] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Accepted: 08/24/2015] [Indexed: 01/02/2023] Open
Abstract
Low absolute lymphocyte count (ALC) to absolute monocyte count (AMC) ratio (ALC/AMC) is an independent prognostic factor in Hodgkin lymphoma (HL), but different cutoffs (1.1, 1.5, and 2.9) have been applied. We aimed to validate the prognostic significance of ALC/AMC in 537 homogenously treated (doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalents ± radiotherapy) classical HL patients at various cutoffs. The median ALC/AMC was 2.24 (0.44-20.50). The median AMC was 0.653 × 10(9)/L (0.050-2.070). Lower ALC/AMC was associated with established markers of adverse prognosis. In total, 477 (89%), 418 (78%), and 189 (35%) patients had an ALC/AMC ratio of ≥1.1, ≥1.5, and ≥2.9; respectively; 20% had monocytosis (≥0.9 × 10(9)/L). Ten-year time to progression (TTP) was 77% versus 55% for patients with ALC/AMC ≥1.1 and <1.1 (p = .0002), 76% versus 68% for ALC/AMC ≥1.5 and <1.5 (p = .049), 77% versus 73% for ALC/AMC ≥2.9 and <2.9 (p = .35), and 79% versus 70% for ALC/AMC ≥2.24 and <2.24 (p = .08), respectively. In stages ΙΑ/ΙΙΑ and in patients ≥60 years old, ALC/AMC had no significant effect on TTP. In advanced stages, ALC/AMC was significant only at the cutoff of 1.1 (10-year TTP 67% vs. 48%; p = .016). In younger, advanced-stage patients, the differences were more pronounced. In multivariate analysis of TTP, ALC/AMC < 1.1 (p = .007) and stage IV (p < .001) were independent prognostic factors; ALC/AMC was independent of International Prognostic Score in another model. ALC/AMC was more predictive of overall survival than TTP. At the cutoff of 1.1, ALC/AMC had independent prognostic value in multivariate analysis. However, the prognostically inferior group comprised only 11% of patients. Further research is needed prior to the widespread use of this promising marker.
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Affiliation(s)
- Theodoros P Vassilakopoulos
- Department of Haematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria N Dimopoulou
- Department of Haematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria K Angelopoulou
- Department of Haematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Kyriaki Petevi
- Department of Haematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | | | | | - Maria Dimou
- First Propedeutic Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - George Boutsikas
- Department of Haematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Alexandros Kanellopoulos
- Department of Haematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Gabriella Gainaru
- Department of Haematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Eleni Plata
- Department of Haematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Pagona Flevari
- Department of Haematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Katerina Koutsi
- Department of Haematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Loula Papageorgiou
- Department of Haematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Vassilios Telonis
- Department of Haematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Panayiotis Tsaftaridis
- Department of Haematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | | | | | | | - Nora-Athina Viniou
- First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Marina P Siakantaris
- First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Eleni Variami
- First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Marie-Christine Kyrtsonis
- First Propedeutic Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - John Meletis
- Department of Haematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Panayiotis Panayiotidis
- First Propedeutic Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Kostas Konstantopoulos
- Department of Haematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Chang C, Wu SY, Kang YW, Lin KP, Chen TY, Medeiros LJ, Chang KC. High levels of regulatory T cells in blood are a poor prognostic factor in patients with diffuse large B-cell lymphoma. Am J Clin Pathol 2015; 144:935-44. [PMID: 26573001 DOI: 10.1309/ajcpujgmvv6zf4gg] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVES Host immunity likely plays a role in preventing progression of diffuse large B-cell lymphoma (DLBCL). Analysis of host immune cells may provide useful information for assessing prognosis or possibly clinical management. METHODS Peripheral blood samples from 77 patients with DLBCL and 30 healthy volunteers were analyzed using flow cytometry immunophenotyping. CBC counts, T-cell subsets, and dendritic cells (DCs) were detected, and the results were correlated with clinicopathologic characteristics. RESULTS Compared with healthy volunteers, patients with DLBCL had significantly higher leukocyte and monocyte counts (P < .001); higher percentages of neutrophils (P < .001), "natural" regulatory T cells (Tregs; CD3+Foxp3+, P < .001), and immature DCs (CD83-CD1a+, P = .005); and lower percentages of lymphocytes (P < .001) and helper T cells (P = .038). In univariate analysis, high neutrophil counts (≥6,000/μL, P = .014) and "induced" Tregs (CD4+CD25+, P = .026) were poor survival factors along with high International Prognostic Index scores (P < .001) and other high-risk clinical parameters. In multivariate analysis, high Tregs retained significance. Suppression of lymphocytes correlated with poor clinical factors; higher natural Tregs correlated with a lower CD4+/CD8+ ratio (P = .035) and more immature DCs (P = .055). CONCLUSIONS Changes in blood immune cells occur in patients with DLBCL. The results also support a suppressive role of Tregs in adaptive immunity and correlate with poor-risk prognostic factors.
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Keane C, Vari F, Hertzberg M, Cao KAL, Green MR, Han E, Seymour JF, Hicks RJ, Gill D, Crooks P, Gould C, Jones K, Griffiths LR, Talaulikar D, Jain S, Tobin J, Gandhi MK. Ratios of T-cell immune effectors and checkpoint molecules as prognostic biomarkers in diffuse large B-cell lymphoma: a population-based study. LANCET HAEMATOLOGY 2015; 2:e445-55. [PMID: 26686046 DOI: 10.1016/s2352-3026(15)00150-7] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Revised: 08/07/2015] [Accepted: 08/07/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND Risk-stratification of diffuse large B-cell lymphoma (DLBCL) requires identification of patients with disease that is not cured, despite initial treatment with R-CHOP. The prognostic importance of the revised International Prognostic Index (R-IPI) and cell of origin of the malignant B cell are established in DLBCL. We aimed to develop a novel, easily applicable, tissue-based prognostic biomarker based on quantification of the tumour microenvironment that is independent of and additive to the R-IPI and cell of origin. METHODS We performed digital hybridisation on the NanoString platform to assess the relation between immune effector and inhibitory (checkpoint) genes in 252 formalin-fixed, paraffin-embedded DLBCL tissue specimens obtained from patients treated with R-CHOP. We used a tree-based survival model to quantify net antitumoral immunity (using ratios of immune effector to checkpoint genes) and to generate a cutoff as an outcome predictor in 158 of the 252 patients. We validated this model in tissue (n=233) and blood (n=140) samples from two independent cohorts treated with R-CHOP. FINDINGS T-cell and NK-cell immune effector molecule expression correlated with tumour-associated macrophage and PD-1/PD-L1 axis markers, consistent with malignant B cells triggering a dynamic checkpoint response to adapt to and evade immune surveillance. The ratio of CD4*CD8 to (CD163:CD68[M2])*PD-L1 was better able to stratify overall survival than was any one immune marker or combination, distinguishing groups with disparate 4-year overall survival. 94 (59%) of 158 patients had a score above the cutoff and 4-year overall survival of 92·1% (95% CI 82·9-96·7), and the remaining 64 (41%) patients had a score below the cutoff and 4-year overall survival of 47·0% (32·8-60·5; hazard ratio [HR] 8·3, 95% CI 4·3-17·3; p<0·0001). The CD4*CD8:M2*PD-L1 immune ratio was independent of and added to the R-IPI and cell of origin. Tissue findings in the independent tissue cohort accorded with those in our initial tissue cohort. 139 (60%) of 233 patients had a score above the cutoff and 4-year overall survival of 75·6% (95% CI 64·6-83·6), with the remaining 94 (40%) patients having a score below the cutoff (63·5% [52·5-72·7]; HR 1·9, 95% CI 1·1-3·3; p=0·0067). INTERPRETATION Ratios of immune effectors to checkpoints augment the cell of origin and R-IPI in DLBCL and are applicable to paraffin-embedded biopsy specimens. These findings might have potential implications for selection of patients for checkpoint blockade within clinical trials. FUNDING Leukaemia Foundation of Queensland, Kasey-Anne Oklobdzijato Memorial Fund, the Australasian Leukaemia and Lymphoma Group (Malcolm Broomhead Bequest), the Australian Cancer Research Foundation, and the Cancer Council of Queensland.
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Affiliation(s)
- Colm Keane
- University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, QLD, Australia; Princess Alexandra Hospital, Brisbane, QLD, Australia; Genomics Research Centre, Griffith University, Southport, QLD, Australia
| | - Frank Vari
- University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, QLD, Australia
| | - Mark Hertzberg
- Department of Haematology, Prince of Wales Hospital, Sydney, NSW, Australia
| | - Kim-Anh Lê Cao
- University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, QLD, Australia
| | - Michael R Green
- Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA
| | - Erica Han
- University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, QLD, Australia
| | - John F Seymour
- Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC, Australia
| | - Rodney J Hicks
- Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC, Australia
| | - Devinder Gill
- University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, QLD, Australia; Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Pauline Crooks
- University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, QLD, Australia
| | - Clare Gould
- University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, QLD, Australia; Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Kimberley Jones
- University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, QLD, Australia
| | - Lyn R Griffiths
- Genomics Research Centre, Griffith University, Southport, QLD, Australia
| | - Dipti Talaulikar
- Canberra Hospital, Canberra, ACT, Australia; Australian National University Medical School, Acton, ACT, Australia
| | | | - Josh Tobin
- Australian National University Medical School, Acton, ACT, Australia
| | - Maher K Gandhi
- University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, QLD, Australia; Princess Alexandra Hospital, Brisbane, QLD, Australia.
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Porrata LF. Adaptive cancer treatment: why I put my money on immunotherapy. Lancet Haematol 2015; 2:e402-e403. [PMID: 26686038 DOI: 10.1016/s2352-3026(15)00189-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Accepted: 08/24/2015] [Indexed: 06/05/2023]
Affiliation(s)
- Luis F Porrata
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
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Myeloid-derived suppressor cells in B cell malignancies. Tumour Biol 2015; 36:7339-53. [DOI: 10.1007/s13277-015-4004-z] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Accepted: 08/25/2015] [Indexed: 02/07/2023] Open
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Chen YM, Lai CH, Chang HC, Chao TY, Tseng CC, Fang WF, Wang CC, Chung YH, Wang YH, Su MC, Huang KT, Chen HC, Chang YC, Lin MC. Baseline and Trend of Lymphocyte-to-Monocyte Ratio as Prognostic Factors in Epidermal Growth Factor Receptor Mutant Non-Small Cell Lung Cancer Patients Treated with First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. PLoS One 2015; 10:e0136252. [PMID: 26313661 PMCID: PMC4552380 DOI: 10.1371/journal.pone.0136252] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Accepted: 08/02/2015] [Indexed: 11/18/2022] Open
Abstract
Background Patients with early-stage lung cancer who have a high baseline lymphocyte-to-monocyte ratio (LMR) have a favorable prognosis. However, the prognostic significance of LMR in patients with advanced-stage EGFR-mutant non-small cell lung cancer (NSCLC) receiving first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has not been established. We conducted a retrospective analysis to investigate the influence of LMR on clinical outcomes including progression-free survival (PFS) and overall survival (OS) in EGFR-mutant patients with NSCLC. Materials and Methods Of 1310 lung cancer patients diagnosed between January 2011 and October 2013, 253 patients receiving first-line EGFR-TKIs for EGFR-mutant NSCLC were included. The cut-off values for baseline and the 1-month-to-baseline ratio of LMR (MBR), determined by using receiver operating characteristic curves, were 3.29 and 0.63, respectively. Patients were divided into 3 prognostic groups: high LMR and MBR, high LMR or MBR, and low LMR and MBR. Results The mean patient age was 65.2 years, and 41% were men. The median PFS and OS were 10.3 and 22.0 months, respectively. The PFS in patients with high LMR and MBR, high LMR or MBR, and low LMR and MBR were 15.4, 7.1, and 2.0 months, respectively (p < 0.001), whereas the OS were 32.6, 13.7, and 5.1 months, respectively (p < 0.001). Conclusion A combination of baseline and trend of LMR can be used to identify patients with a high mortality risk in EGFR-mutant NSCLC patients receiving first-line EGFR-TKIs.
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Affiliation(s)
- Yu-Mu Chen
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hao Lai
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Huang-Chih Chang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tung-Ying Chao
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chia-Cheng Tseng
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Wen-Feng Fang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Department of Respiratory Care, Chang Gung Institute of Technology, Chiayi, Taiwan
| | - Chin-Chou Wang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yu-Hsiu Chung
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Hsi Wang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Mao-Chang Su
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kuo-Tung Huang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hung-Chen Chen
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ya-Chun Chang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Meng-Chih Lin
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
- * E-mail:
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Peripheral blood lymphocyte to monocyte ratio identifies high-risk adult patients with sporadic Burkitt lymphoma. Ann Hematol 2015; 94:1645-54. [PMID: 26082333 DOI: 10.1007/s00277-015-2427-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2015] [Accepted: 06/09/2015] [Indexed: 01/29/2023]
Abstract
Adult sporadic Burkitt lymphoma (BL) is a rare subtype of lymphoma. In this retrospective study, we investigated the prognostic value of pretreatment lymphocyte to monocyte ratio (LMR) in a cohort of 62 patients. Using LMR <2.6 as the optimal cutoff point, 24 patients (38.7 %) had LMR <2.6. The complete response rates in high-LMR group and low-LMR group were 90.9 and 65.0 %, respectively (P = 0.019). At a median follow-up time of 41 months, the 3-year progression-free survival (PFS) rate and overall survival (OS) rates were 76 and 80 %, respectively. In a multivariate Cox regression model, it was found that the presence of bone marrow infiltration and low LMR were independently adverse prognostic factors for both PFS and OS. In the whole group, the addition of rituximab to treatment did not benefit patients significantly in PFS and OS. In subgroup analysis, in patients with high LMR, addition of rituximab can significantly improve survival outcomes (P = 0.046). In conclusion, we firstly found that low LMR (<2.60) was an independently adverse prognostic factor in adult patients with sporadic BL. Intensive chemotherapy could cure the majority of patients in our study, and the pretreatment LMR might predict the value of rituximab in this age population.
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An Elevated Peripheral Blood Monocyte-to-Lymphocyte Ratio Predicts Poor Prognosis in Patients with Primary Pulmonary Lymphoepithelioma-Like Carcinoma. PLoS One 2015; 10:e0126269. [PMID: 25950432 PMCID: PMC4423962 DOI: 10.1371/journal.pone.0126269] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Accepted: 03/31/2015] [Indexed: 12/14/2022] Open
Abstract
Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer. In this study, we retrospectively reviewed the data from 74 consecutive patients with pulmonary LELC and investigated the prognostic value of pretreatment monocyte-to-lymphocyte ratio (MLR). The cut-off value determined by ROC curve for MLR was 0.262. According to this cut-off value, 36 (48.6%) patients had lower MLR value (<0.262) at diagnosis. There was no significant correlation between MLR level and gender, age, smoking history, stage, and lactate dehydrogenase (LDH) level. The 2-year, 5-year, and 10-year OS rate were 86%, 72%, and 61%, respectively; the 2-year, 5-year, and 10-year PFS rate were 71%, 63%, and 49%, respectively. In univariate analysis, advanced stage, elevated LDH level, and higher MLR value (> = 0.262) were significantly associated with poor OS and PFS. In a multivariate Cox regression model that included stage, LDH and MLR level, all of these three factors were found to be independent prognostic factors for both PFS and OS. In patients who received radical surgery, MLR level remained significantly correlated with OS and PFS. In conclusion, we firstly demonstrated that pretreatment MLR can be used as a useful independent prognostic marker in patients with pulmonary LELC, and might guide us to optimize the treatment strategies. However, due to the relatively rarity of this disease and the limitation of a retrospective study, further prospective studies performed in multicenter are necessary to validate the prognostic value of MLR in pulmonary LELC.
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Szerafin L, Jakó J, Riskó F. [Prognostic value of absolute monocyte count in chronic lymphocytic leukaemia]. Orv Hetil 2015; 156:592-7. [PMID: 25845318 DOI: 10.1556/oh.2015.30126] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
INTRODUCTION The low peripheral absolute lymphocyte and high monocyte count have been reported to correlate with poor clinical outcome in various lymphomas and other cancers. However, a few data known about the prognostic value of absolute monocyte count in chronic lymphocytic leukaemia. AIM The aim of the authors was to investigate the impact of absolute monocyte count measured at the time of diagnosis in patients with chronic lymphocytic leukaemia on the time to treatment and overal survival. METHOD Between January 1, 2005 and December 31, 2012, 223 patients with newly-diagnosed chronic lymphocytic leukaemia were included. The rate of patients needing treatment, time to treatment, overal survival and causes of mortality based on Rai stages, CD38, ZAP-70 positivity and absolute monocyte count were analyzed. RESULTS Therapy was necessary in 21.1%, 57.4%, 88.9%, 88.9% and 100% of patients in Rai stage 0, I, II, III an IV, respectively; in 61.9% and 60.8% of patients exhibiting CD38 and ZAP-70 positivity, respectively; and in 76.9%, 21.2% and 66.2% of patients if the absolute monocyte count was <0.25 G/l, between 0.25-0.75 G/l and >0.75 G/l, respectively. The median time to treatment and the median overal survival were 19.5, 65, and 35.5 months; and 41.5, 65, and 49.5 months according to the three groups of monocyte counts. The relative risk of beginning the therapy was 1.62 (p<0.01) in patients with absolute monocyte count <0.25 G/l or >0.75 G/l, as compared to those with 0.25-0.75 G/l, and the risk of overal survival was 2.41 (p<0.01) in patients with absolute monocyte count lower than 0.25 G/l as compared to those with higher than 0.25 G/l. The relative risks remained significant in Rai 0 patients, too. The leading causes of mortality were infections (41.7%) and the chronic lymphocytic leukaemia (58.3%) in patients with low monocyte count, while tumours (25.9-35.3%) and other events (48.1 and 11.8%) occurred in patients with medium or high monocyte counts. CONCLUSIONS Patients with low and high monocyte counts had a shorter time to treatment compared to patients who belonged to the intermediate monocyte count group. The low absolute monocyte count was associated with increased mortality caused by infectious complications and chronic lymphocytic leukaemia. The absolute monocyte count may give additional prognostic information in Rai stage 0, too.
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Affiliation(s)
- László Szerafin
- Szabolcs-Szatmár-Bereg Megyei Jósa András Oktatókórház Hematológiai Osztály Nyíregyháza Szent István u. 68. 4400
| | - János Jakó
- Szabolcs-Szatmár-Bereg Megyei Jósa András Oktatókórház Hematológiai Osztály Nyíregyháza Szent István u. 68. 4400
| | - Ferenc Riskó
- Szabolcs-Szatmár-Bereg Megyei Jósa András Oktatókórház Sürgősségi Betegellátó Centrum Nyíregyháza
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Eo WK, Jeong DW, Chang HJ, Won KY, Choi SI, Kim SH, Chun SW, Oh YL, Lee TH, Kim YO, Kim KH, Ji YI, Kim A, Kim HY. Absolute monocyte and lymphocyte count prognostic score for patients with gastric cancer. World J Gastroenterol 2015; 21:2668-2676. [PMID: 25759535 PMCID: PMC4351217 DOI: 10.3748/wjg.v21.i9.2668] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2014] [Revised: 10/16/2014] [Accepted: 12/08/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To measure the prognostic significance of absolute monocyte count/absolute lymphocyte count prognostic score (AMLPS) in patients with gastric cancer.
METHODS: We retrospectively examined the combination of absolute monocyte count (AMC) and absolute lymphocyte count (ALC) as prognostic variables in a cohort of 299 gastric cancer patients who underwent surgical resection between 2006 and 2013 and were followed at a single institution. Both AMC and ALC were dichotomized into two groups using cut-off points determined by receiving operator characteristic curve analysis. An AMLPS was generated, which stratified patients into three risk groups: low risk (both low AMC and high ALC), intermediate risk (either high AMC or low ALC), and high risk (both high AMC and low ALC). The primary objective of the study was to validate the impact of AMLPS on both disease-free survival (DFS) and overall survival (OS), and the second objective was to assess the AMLPS as an independent prognostic factor for survival in comparison with known prognostic factors.
RESULTS: Using data from the entire cohort, the most discriminative cut-off values of AMC and ALC selected on the receiver operating characteristic curve were 672.4/μL and 1734/μL for DFS and OS. AMLPS risk groups included 158 (52.8%) patients in the low-risk, 128 (42.8%) in the intermediate-risk, and 13 (4.3%) in the high-risk group. With a median follow-up of 37.2 mo (range: 1.7-91.4 mo), five-year DFS rates in the low-, intermediate-, and high-risk groups were 83.4%, 78.7%, and 19.8%, respectively. And five-year OS rates in the low-, intermediate-, and high-risk groups were 89.3%, 81.1%, and 14.4%, respectively. On multivariate analysis performed with patient- and tumor-related factors, we identified AMLPS, age, and pathologic tumor-node-metastasis stage as the most valuable prognostic factors impacting DFS and OS.
CONCLUSION: AMLPS identified patients with a poor DFS and OS, and it was independent of age, pathologic stage, and various inflammatory markers.
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Lin B, Chen C, Qian Y, Feng J. Prognostic role of peripheral blood lymphocyte/monocyte ratio at diagnosis in diffuse large B-cell lymphoma: a meta-analysis. Leuk Lymphoma 2015; 56:2563-8. [PMID: 25686648 DOI: 10.3109/10428194.2015.1014367] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
To evaluate the prognostic value of the absolute lymphocyte count/absolute monocyte count ratio (ALC/AMC ratio) at diagnosis in diffuse large B-cell lymphoma (DLBCL), we performed a meta-analysis of published studies that provided survival information with reference to the ALC/AMC ratio at diagnosis. Nine studies covering a total of 4198 subjects were included in this analysis. The summary hazard ratios of low ALC/AMC ratio for overall survival were 2.00 (p = 0.000) in the population that received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and 1.12 (p = 0.479) in the population that received CHOP. The corresponding ratios for event-free survival and progression-free survival were 1.93 (p = 0.000) and 2.31 (p = 0.000) in the population that received R-CHOP. These results may justify risk-adapted therapeutic strategies for patients with DLBCL treated with R-CHOP to account for the ALC/AMC ratio at diagnosis.
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Affiliation(s)
- Baochai Lin
- a Division of Radiation Oncology and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , P. R. China
| | - Cuie Chen
- b Division of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , P. R. China
| | - Yan Qian
- b Division of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , P. R. China
| | - Jianhua Feng
- c Division of Pediatric Hematology-Oncology, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , P. R. China
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Younos IH, Abe F, Talmadge JE. Myeloid-derived suppressor cells: their role in the pathophysiology of hematologic malignancies and potential as therapeutic targets. Leuk Lymphoma 2015; 56:2251-63. [PMID: 25407654 DOI: 10.3109/10428194.2014.987141] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells at various stages of differentiation/maturation that have a role in cancer induction and progression. They function as vasculogenic and immunosuppressive cells, utilizing multiple mechanisms to block both innate and adaptive anti-tumor immunity. Recently, their mechanism of action and clinical importance have been defined, and the cross-talk between myeloid cells and cancer cells has been shown to contribute to tumor induction, progression, metastasis and tolerance. In this review, we focus on the role of MDSCs in hematologic malignancies and the therapeutic approaches targeting MDSCs that are currently in clinical studies.
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Affiliation(s)
- Ibrahim H Younos
- a Department of Clinical Pharmacology , Menoufia University , Al-Minufya , Egypt.,b Department of Pharmacology and Clinical Pharmacy , College of Medicine and Health Sciences, Sultan Qaboos University , Muscat , Oman
| | - Fuminori Abe
- c SBI Pharmaceuticals Co., Ltd. , Tokyo 106-6020 , Japan
| | - James E Talmadge
- d Department of Pathology and Microbiology , Nebraska Medical Center , Omaha , NE , USA
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Vaidya R, Witzig TE. Prognostic factors for diffuse large B-cell lymphoma in the R(X)CHOP era. Ann Oncol 2014; 25:2124-2133. [PMID: 24625454 PMCID: PMC4288137 DOI: 10.1093/annonc/mdu109] [Citation(s) in RCA: 129] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Revised: 01/27/2014] [Accepted: 03/03/2014] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The introduction of rituximab (R) to conventional CHOP chemotherapy for newly diagnosed diffuse large B-cell lymphoma (DLBCL) led to an unequivocal improvement in survival, establishing RCHOP as the standard of care. Still, nearly 40% of DLBCL patients will eventually die of relapsed disease. Efforts to improve outcomes by addition of new biologic agents (X) to the RCHOP backbone are underway. In this era of R(X)CHOP, it is imperative to develop prognostic and predictive markers, not only to identify patients who will suffer a particularly aggressive course, but also to accurately select patients for clinical trials from which they will most benefit. DESIGN The following review was undertaken to describe prognostic factors in DLBCL, with emphasis on markers that are accurate, relatively available, and clinically applicable in 2014. RESULTS The International Prognostic Index retains its validity in the era of RCHOP, although with limited ability to predict those with <50% chance of long-term survival. Gene expression profiling has provided novel insights into the biology of DLBCL and led to the development of immunohistochemistry (IHC) algorithms that are in routine practice. Identification of a 'double-hit' (DH) lymphoma by fluorescent in situ hybridization with aberrations involving MYC and/or BCL2 and BCL6 genes has important implications due to its extremely dismal prognosis with RCHOP. Other markers such as the absolute lymphocyte count (ALC), serum immunoglobulin free light chains, vitamin D levels, serum cytokines/chemokines, and imaging with positron emission tomography (PET) have all shown promise as future predictive/prognostic tests. CONCLUSIONS The future for new treatment options in DLBCL is promising with current clinical trials testing novel targeted agents such as bortezomib, lenalidomide, and ibrutinib as the 'X' in R(X)CHOP. Predictive factors are required to select and randomize patients appropriately for these trials. We envision the day when 'X' will be chosen based on the biological characteristics of the tumor.
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MESH Headings
- Antibodies, Monoclonal, Murine-Derived/administration & dosage
- Antineoplastic Combined Chemotherapy Protocols/administration & dosage
- Clinical Trials as Topic
- Cyclophosphamide/administration & dosage
- Doxorubicin/administration & dosage
- Doxorubicin/analogs & derivatives
- Humans
- Immunoglobulin Light Chains/blood
- In Situ Hybridization, Fluorescence
- Lymphocyte Count
- Lymphoma, Large B-Cell, Diffuse/blood
- Lymphoma, Large B-Cell, Diffuse/drug therapy
- Lymphoma, Large B-Cell, Diffuse/genetics
- Lymphoma, Large B-Cell, Diffuse/pathology
- Monocytes/pathology
- Prednisone/administration & dosage
- Prognosis
- Proto-Oncogene Proteins c-bcl-2/biosynthesis
- Proto-Oncogene Proteins c-myc/biosynthesis
- Rituximab
- Treatment Outcome
- Vincristine/administration & dosage
- Vitamin D/blood
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Affiliation(s)
- R Vaidya
- Department of Internal Medicine, Division of Hematology, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, USA
| | - T E Witzig
- Department of Internal Medicine, Division of Hematology, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, USA.
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Hu P, Shen H, Wang G, Zhang P, Liu Q, Du J. Prognostic significance of systemic inflammation-based lymphocyte- monocyte ratio in patients with lung cancer: based on a large cohort study. PLoS One 2014; 9:e108062. [PMID: 25275631 PMCID: PMC4183469 DOI: 10.1371/journal.pone.0108062] [Citation(s) in RCA: 116] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2014] [Accepted: 08/19/2014] [Indexed: 12/17/2022] Open
Abstract
Increasing evidence indicates cancer-related inflammatory biomarkers show great promise for predicting the outcome of cancer patients. The lymphocyte- monocyte ratio (LMR) was demonstrated to be independent prognostic factor mainly in hematologic tumor. The aim of the present study was to investigate the prognostic value of LMR in operable lung cancer. We retrospectively enrolled a large cohort of patients with primary lung cancer who underwent complete resection at our institution from 2006 to 2011. Inflammatory biomarkers including lymphocyte count and monocyte count were collected from routinely performed preoperative blood tests and the LMR was calculated. Survival analyses were calculated for overall survival (OS) and disease-free survival (DFS). A total of 1453 patients were enrolled in the study. The LMR was significantly associated with OS and DFS in multivariate analyses of the whole cohort (HR = 1.522, 95% CI: 1.275-1.816 for OS, and HR = 1.338, 95% CI: 1.152-1.556 for DFS). Univariate subgroup analyses disclosed that the prognostic value was limited to patients with non-small-cell lung cancer (NSCLC) (HR: 1.824, 95% CI: 1.520-2.190), in contrast to patients with small cell lung cancer (HR: 1.718, 95% CI: 0.946-3.122). Multivariate analyses demonstrated that LMR was still an independent prognostic factor in NSCLC. LMR can be considered as a useful independent prognostic marker in patients with NSCLC after complete resection. This will provide a reliable and convenient biomarker to stratify high risk of death in patients with operable NSCLC.
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Affiliation(s)
- Pingping Hu
- Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, China
| | - Hongchang Shen
- Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, China
| | - Guanghui Wang
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, China
| | - Ping Zhang
- Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, China
| | - Qi Liu
- Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, China
| | - Jiajun Du
- Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, China
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, China
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Procházka V, Pytlík R, Janíková A, Belada D, Šálek D, Papajík T, Campr V, Fürst T, Furstova J, Trněný M. A new prognostic score for elderly patients with diffuse large B-cell lymphoma treated with R-CHOP: the prognostic role of blood monocyte and lymphocyte counts is absent. PLoS One 2014; 9:e102594. [PMID: 25058337 PMCID: PMC4109941 DOI: 10.1371/journal.pone.0102594] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2014] [Accepted: 06/20/2014] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Absolute lymphocyte count (ALC) and absolute monocyte count (AMC) have been documented as independent predictors of survival in patients with newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL). Analysis of the prognostic impact of ALC and AMC in the context of International Prognostic Index (IPI) and other significant variables in elderly population treated in the R-CHOP regime has not been carried out yet. METHODOLOGY/PRINCIPAL FINDINGS In this retrospective study, a cohort of 443 newly diagnosed DLBCL patients with age ≥ 60 was analyzed. All patients were treated with the R-CHOP therapy. An extensive statistical analysis was performed to identify risk factors of 3-year overall survival (OS). In multivariate analysis, only three predictors proved significant: Eastern Cooperative Oncology Group performance status (ECOG), age and bulky disease presence. These predictors were dichotomized (ECOG ≥ 1, age ≥ 70, bulk ≥ 7.5) to create a novel four-level score. This score predicted 3-year OS of 94.0%, 77.4%, 62.7% and 35.4% in the low-, low-intermediate, high-intermediate and high-risk groups, respectively (P<0.001). Further, a three-level score was tested which stratifies the population better (3-year OS: 91.9%, 67.2%, 36.2% in the low, intermediate and high-risk groups, respectively) but is more difficult to interpret. Both the 3- and 4-level scores were compared to standard scoring systems and, in our population, were shown to be superior in terms of patients risk stratification with respect to 3-year OS prediction. The results were successfully validated on an independent cohort of 162 patients of similar group characteristics. CONCLUSIONS The prognostic role of baseline ALC, AMC or their ratio (LMR) was not confirmed in the multivariate context in elderly population with DLBCL treated with R-CHOP. The newly proposed age-specific index stratifies the elderly population into risk groups more precisely than the conventional IPI and its existing variants.
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MESH Headings
- Age Factors
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal, Murine-Derived/administration & dosage
- Antineoplastic Combined Chemotherapy Protocols/administration & dosage
- Biomarkers/analysis
- Cyclophosphamide/administration & dosage
- Doxorubicin/administration & dosage
- Female
- Humans
- Leukocyte Count
- Lymphocytes/pathology
- Lymphoma, Large B-Cell, Diffuse/diagnosis
- Lymphoma, Large B-Cell, Diffuse/drug therapy
- Lymphoma, Large B-Cell, Diffuse/mortality
- Lymphoma, Large B-Cell, Diffuse/pathology
- Male
- Middle Aged
- Monocytes/pathology
- Prednisone/administration & dosage
- Prognosis
- Research Design/statistics & numerical data
- Retrospective Studies
- Risk Factors
- Rituximab
- Survival Analysis
- Vincristine/administration & dosage
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Affiliation(s)
- Vít Procházka
- Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic
| | - Robert Pytlík
- First Internal Department, Charles University General Hospital, Prague, Czech Republic
| | - Andrea Janíková
- Department of Internal Medicine-Hematooncology, University Hospital Brno, and Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - David Belada
- Second Department of Medicine, Department of Hematology, University Hospital and Faculty of Medicine, Hradec Králové, Czech Republic
| | - David Šálek
- Department of Internal Medicine-Hematooncology, University Hospital Brno, and Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Tomáš Papajík
- Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic
| | - Vít Campr
- Department of Pathology and Molecular Medicine, Charles University, and Second Medical School and Faculty Hospital in Motol, Prague, Czech Republic
| | - Tomáš Fürst
- Department of Mathematical Analysis and Applications of Mathematics, Faculty of Science, Palacký University, Olomouc, Czech Republic
| | - Jana Furstova
- Department of Mathematical Analysis and Applications of Mathematics, Faculty of Science, Palacký University, Olomouc, Czech Republic
- * E-mail:
| | - Marek Trněný
- First Internal Department, Charles University General Hospital, Prague, Czech Republic
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Abstract
Relapsed-Refractory Diffuse Large B Cell Lymphoma (RR DLBCL), which accounts for approximately one-third of patients with DLBCL, remains a major cause of morbidity and mortality. Managing RR DLBCL continues to be a challenge to the treating hemato-oncologist. Salvage high-dose chemotherapy followed by autologous stem cell transplantation is the standard of care for chemosensitive relapses in DLBCL. Various salvage regimens are available, but the quest for an optimal regimen continues. The addition of rituximab to the salvage regimen has improved the outcome of RR DLBCL. Several pertinent issues regarding the management of RR DLBCL are discussed in this short review.
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Affiliation(s)
- Lalit S Raut
- Institute of Haematology and Transfusion Medicine, Medical College and Hospital, Kolkata, West Bengal, India
| | - Prantar P Chakrabarti
- Institute of Haematology and Transfusion Medicine, Medical College and Hospital, Kolkata, West Bengal, India
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Read JA, Koff JL, Nastoupil LJ, Williams JN, Cohen JB, Flowers CR. Evaluating cell-of-origin subtype methods for predicting diffuse large B-cell lymphoma survival: a meta-analysis of gene expression profiling and immunohistochemistry algorithms. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2014; 14:460-467.e2. [PMID: 25052052 DOI: 10.1016/j.clml.2014.05.002] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Accepted: 05/23/2014] [Indexed: 11/29/2022]
Abstract
BACKGROUND Patients with DLBCL exhibit widely divergent outcomes despite harboring histologically identical tumors. Currently, GEP and IHC algorithms assign patients to 1 of 2 main subtypes: germinal center B cell-like (GCB), or activated B cell-like (ABC), the latter of which historically carries a less favorable prognosis. However, it remains controversial as to whether these prognostic groupings remain valid in the era of rituximab therapy. MATERIALS AND METHODS A systematic literature review identified 24 articles from which meta-analyses were conducted, comparing survival outcomes for patients assigned to either GCB or ABC/non-GCB subtype using GEP and/or Hans, Choi, or Muris IHC algorithms. RESULTS Patients designated as GCB DLBCL using GEP fared significantly better in terms of overall survival than those with ABC DLBCL (hazard ratio, 1.85; P < .0001). In contrast, the Hans and Choi algorithms failed to identify significant differences in overall survival (P = .07 and P = .76, respectively) between GCB and non-GCB groups. CONCLUSIONS Our study illustrates a lack of evidence supporting the use of the Hans and Choi algorithms for stratifying patients into distinct prognostic groups. Rather, GEP remains the preferred method for predicting the course of a patient's disease and informing decisions regarding treatment options.
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Affiliation(s)
- Jay A Read
- Emory University School of Medicine, Atlanta, GA
| | - Jean L Koff
- Emory University School of Medicine, Atlanta, GA
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Wei X, Huang F, Wei Y, Jing H, Xie M, Hao X, Feng R. Low lymphocyte-to-monocyte ratio predicts unfavorable prognosis in non-germinal center type diffuse large B-cell lymphoma. Leuk Res 2014; 38:694-8. [DOI: 10.1016/j.leukres.2014.03.013] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Revised: 03/09/2014] [Accepted: 03/16/2014] [Indexed: 01/01/2023]
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Shin SJ, Roh J, Kim M, Jung MJ, Koh YW, Park CS, Yoon DH, Suh C, Park CJ, Chi HS, Huh J. Prognostic significance of absolute lymphocyte count/absolute monocyte count ratio at diagnosis in patients with multiple myeloma. KOREAN JOURNAL OF PATHOLOGY 2013; 47:526-33. [PMID: 24421845 PMCID: PMC3887154 DOI: 10.4132/koreanjpathol.2013.47.6.526] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/19/2013] [Revised: 10/02/2013] [Accepted: 10/10/2013] [Indexed: 01/17/2023]
Abstract
Background Absolute lymphocyte count (ALC) in peripheral blood has recently been reported to be an independent prognostic factor in multiple myeloma (MM). Previous studies indicated that the absolute monocyte count (AMC) in peripheral blood reflects the state of the tumor microenvironment in lymphomas. Neither the utility of the AMC nor its relationship with ALC has been studied in MM. Methods The prognostic value of ALC, AMC, and the ALC/AMC ratio at the time of diagnosis was retrospectively examined in 189 patients with MM. Results On univariate analysis, low ALC (<1,400 cells/µL), high AMC (≥490 cells/µL), and low ALC/AMC ratio (<2.9) were correlated with worse overall survival (OS) (p=.002, p=.038, and p=.001, respectively). On multivariate analysis, the ALC/AMC ratio was an independent prognostic factor (p=.047), whereas ALC and AMC were no longer statistical significant. Low ALC, high AMC, and low ALC/AMC ratio were associated with poor prognostic factors such as high International Staging System stage, plasmablastic morphology, hypoalbuminemia, and high β2-microglobulin. Conclusions Univariate analysis demonstrated that changes in ALC, AMC, and the ALC/AMC ratio are associated with patient survival in MM. Multivariate analysis showed that, of these factors, the ALC/AMC ratio was an independent prognostic factor for OS.
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Affiliation(s)
- Su-Jin Shin
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin Roh
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Misung Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Min Jung Jung
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young Wha Koh
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chan-Sik Park
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dok Hyun Yoon
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Cheolwon Suh
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chan-Jeong Park
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyun Sook Chi
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jooryung Huh
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Peripheral blood lymphocyte/monocyte ratio predicts outcome for patients with diffuse large B cell lymphoma after standard first-line regimens. Ann Hematol 2013; 93:617-26. [PMID: 24141331 DOI: 10.1007/s00277-013-1916-9] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Accepted: 09/26/2013] [Indexed: 02/06/2023]
Abstract
To determine whether peripheral blood absolute lymphocyte/absolute monocyte counts ratio (ALC/AMC ratio) at diagnosis predicts survival of diffuse large B cell lymphoma (DLBCL) patients treated with standard first-line regimens, we retrospectively analyzed 244 patients with DLBCL who were treated with standard cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, or rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone. Progression-free survival and overall survival (PFS and OS) were estimated using the Kaplan-Meier method and two-tailed log-rank; The Cox proportional hazards model was used to evaluate ALC/AMC ratio as prognostic factors when adjusting for the International Prognostic Index (IPI). On univariate and multivariate analyses performed with factors included in the IPI, the ALC/AMC ratio at diagnosis remained an independent predictor of OS and PFS (OS: P < 0.001; PFS: P < 0.001). Patients with lower ALC/AMC ratio (<3.8) seemed to have lower complete remission rate, 2-year PFS and 3-year OS when compared to patients with ALC/AMC ratio ≥3.8, respectively (26 versus 90 %, P < 0.001; 18 versus 82 %, P < 0.001; 24 versus 86 %; P < 0.001, respectively). Moreover, the ALC/AMC ratio was able to further risk-stratify IPI 0-2 and three-five risk patient groups, respectively. The ALC/AMC ratio at the time of diagnosis may provide additional prognostic information beyond that of the IPI for patients with DLBCL who receive standard first-line regimens.
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Gharbaran R, Goy A, Tanaka T, Park J, Kim C, Hasan N, Vemulapalli S, Sarojini S, Tuluc M, Nalley K, Bhattacharyya P, Pecora A, Suh KS. Fibroblast growth factor-2 (FGF2) and syndecan-1 (SDC1) are potential biomarkers for putative circulating CD15+/CD30+ cells in poor outcome Hodgkin lymphoma patients. J Hematol Oncol 2013; 6:62. [PMID: 23988031 PMCID: PMC3766006 DOI: 10.1186/1756-8722-6-62] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Accepted: 08/19/2013] [Indexed: 12/13/2022] Open
Abstract
Background High risk, unfavorable classical Hodgkin lymphoma (cHL) includes those patients with primary refractory or early relapse, and progressive disease. To improve the availability of biomarkers for this group of patients, we investigated both tumor biopsies and peripheral blood leukocytes (PBL) of untreated (chemo-naïve, CN) Nodular Sclerosis Classic Hodgkin Lymphoma (NS-cHL) patients for consistent biomarkers that can predict the outcome prior to frontline treatment. Methods and materials Bioinformatics data mining was used to generate 151 candidate biomarkers, which were screened against a library of 10 HL cell lines. Expression of FGF2 and SDC1 by CD30+ cells from HL patient samples representing good and poor outcomes were analyzed by qRT-PCR, immunohistochemical (IHC), and immunofluorescence analyses. Results To identify predictive HL-specific biomarkers, potential marker genes selected using bioinformatics approaches were screened against HL cell lines and HL patient samples. Fibroblast Growth Factor-2 (FGF2) and Syndecan-1 (SDC1) were overexpressed in all HL cell lines, and the overexpression was HL-specific when compared to 116 non-Hodgkin lymphoma tissues. In the analysis of stratified NS-cHL patient samples, expression of FGF2 and SDC1 were 245 fold and 91 fold higher, respectively, in the poor outcome (PO) group than in the good outcome (GO) group. The PO group exhibited higher expression of the HL marker CD30, the macrophage marker CD68, and metastatic markers TGFβ1 and MMP9 compared to the GO group. This expression signature was confirmed by qualitative immunohistochemical and immunofluorescent data. A Kaplan-Meier analysis indicated that samples in which the CD30+ cells carried an FGF2+/SDC1+ immunophenotype showed shortened survival. Analysis of chemo-naive HL blood samples suggested that in the PO group a subset of CD30+ HL cells had entered the circulation. These cells significantly overexpressed FGF2 and SDC1 compared to the GO group. The PO group showed significant down-regulation of markers for monocytes, T-cells, and B-cells. These expression signatures were eliminated in heavily pretreated patients. Conclusion The results suggest that small subsets of circulating CD30+/CD15+ cells expressing FGF2 and SDC1 represent biomarkers that identify NS-cHL patients who will experience a poor outcome (primary refractory and early relapsing).
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Affiliation(s)
- Rajendra Gharbaran
- John Theurer Cancer Center, Hackensack University Medical Center, D, Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ 07601, USA.
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Patnaik MM, Padron E, LaBorde RR, Lasho TL, Finke CM, Hanson CA, Hodnefield JM, Knudson RA, Ketterling RP, Al-kali A, Pardanani A, Ali NA, Komrokji RS, Tefferi A. Mayo prognostic model for WHO-defined chronic myelomonocytic leukemia: ASXL1 and spliceosome component mutations and outcomes. Leukemia 2013; 27:1504-10. [PMID: 23531518 DOI: 10.1038/leu.2013.88] [Citation(s) in RCA: 170] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2013] [Accepted: 03/20/2013] [Indexed: 12/12/2022]
Abstract
We evaluated the prognostic relevance of several clinical and laboratory parameters in 226 Mayo Clinic patients with chronic myelomonocytic leukemia (CMML): 152 (67%) males and median age 71 years. At a median follow-up of 15 months, 166 (73%) deaths and 33 (14.5%) leukemic transformations were documented. In univariate analysis, significant risk factors for survival included anemia, thrombocytopenia, increased levels of white blood cells, absolute neutrophils, absolute monocyte count (AMC), absolute lymphocytes, peripheral blood and bone marrow blasts, and presence of circulating immature myeloid cells (IMCs). Spliceosome component (P=0.4) and ASXL1 mutations (P=0.37) had no impact survival. On multivariable analysis, increased AMC (>10 × 10(9)/l, relative risk (RR) 2.5, 95% confidence interval (CI) 1.7-3.8), presence of circulating IMC (RR 2.0, 95% CI 1.4-2.7), decreased hemoglobin (<10 g/dl, RR 1.6, 99% CI 1.2-2.2) and decreased platelet count (<100 × 10(9)/l, RR 1.4, 99% CI 1.0-1.9) remained significant. Using these four risk factors, a new prognostic model for overall (high risk, RR 4.4, 95% CI 2.9-6.7; intermediate risk, RR 2.0, 95% CI 1.4-2.9) and leukemia-free survival (high risk, RR 4.9, 95% CI 1.9-12.8; intermediate risk, RR 2.6, 95% CI 1.1-5.9) performed better than other conventional risk models and was validated in an independent cohort of 268 CMML patients.
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Affiliation(s)
- M M Patnaik
- Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
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von Hohenstaufen KA, Conconi A, de Campos CP, Franceschetti S, Bertoni F, Margiotta Casaluci G, Stathis A, Ghielmini M, Stussi G, Cavalli F, Gaidano G, Zucca E. Prognostic impact of monocyte count at presentation in mantle cell lymphoma. Br J Haematol 2013; 162:465-73. [PMID: 23808798 DOI: 10.1111/bjh.12409] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2013] [Accepted: 05/02/2013] [Indexed: 11/29/2022]
Abstract
An increased number of circulating monocytes at presentation has recently been associated with shorter survival in Hodgkin lymphoma, follicular lymphoma and diffuse large B cell lymphoma. This study aimed to assess the prognostic impact of the absolute monocyte count (AMC) at diagnosis in mantle cell lymphoma (MCL). AMC at diagnosis was available in 97 MCL cases recorded in the databases of the Oncology Institute of Southern Switzerland in Bellinzona (Switzerland) and the Division of Haematology of the Amedeo Avogadro University of Eastern Piedmont in Novara (Italy). With a median follow up of 7 years, the 5-year overall survival was 29% for patients with AMC >0·50 × 10(9) /l and 62% for patients with AMC ≤0·50 × 10(9) /l (P = 0·008). Elevated AMC and beta-2 microglobulin at diagnosis remained independent outcome predictors at multivariate analysis, controlling for the MCL International Prognostic Index (MIPI), and have been used to build a simple prognostic scoring system. In this relatively small and heterogeneous series an increased AMC identified poor-risk patients. Our results suggest that AMC together with the beta-2 microglobulin level might provide an inexpensive way to stratify MCL patient risk as a complement to the MIPI, which was confirmed to be a very powerful prognostic tool.
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Peripheral blood absolute lymphocyte/monocyte ratio recovery during ABVD treatment cycles predicts clinical outcomes in classical Hodgkin lymphoma. Blood Cancer J 2013; 3:e110. [PMID: 23599022 PMCID: PMC3641323 DOI: 10.1038/bcj.2013.8] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
The peripheral blood absolute lymphocyte/monocyte count ratio at diagnosis (ALC/AMC-DX) predicts survival in classical Hodgkin lymphoma (cHL). However, a limitation of the ALC/AMC-DX is the inability to assess sequentially the host/tumor interaction during treatment. Therefore, we retrospectively examined the ALC/AMC ratio, as a surrogate marker of host immunity (ALC) and tumor microenvironment (AMC), at each adriamycin, bleomycin, vinblastine and dacarbazine treatment cycle as a predictor for clinical outcomes. From 1990 until 2008, 190 cHL patients were diagnosed, treated and followed at Mayo Clinic Rochester and qualified for the study. The ALC/AMC ratio at each treatment cycle was a predictor for overall survival (OS) and progression-free survival (PFS). An ALC/AMC ratio 1.1 versus ALC/AMC <1.1 during treatment cycles was an independent predictor for OS (hazard ratio (HR)=0.14; 95% confidence interval (CI): 0.04-0.40; P<0.0002) and for PFS (HR=0.19; 95% CI: 0.05-0.82; P<0.03). The ALC/AMC ratio during treatment cycles is a predictor for survival and provides a platform to develop therapeutic modalities to manipulate the ALC/AMC ratio during chemotherapy to improve clinical outcomes in cHL.
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Bari A, Tadmor T, Sacchi S, Marcheselli L, Liardo EV, Pozzi S, Luminari S, Baldini L, Marmiroli S, Federico M, Polliack A. Monocytosis has adverse prognostic significance and impacts survival in patients with T-cell lymphomas. Leuk Res 2013; 37:619-23. [PMID: 23395384 DOI: 10.1016/j.leukres.2013.01.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2012] [Revised: 01/10/2013] [Accepted: 01/14/2013] [Indexed: 11/29/2022]
Abstract
In this retrospective study we evaluated the prognostic impact of peripheral blood monocytosis in patients with T-cell non Hodgkin lymphomas with "aggressive-typically nodal presentation". In this dataset monocytes >0.8 × 10(9)/L had a strong and statistically significant negative impact on overall survival (OS). In univariate analysis several parameters, including age >60 years, advanced stage, bone marrow involvement, ECOG PS >1, high LDH level, monocytes >0.8 × 10(9)/L, hemoglobin<120 g/L, albumin<35 g/L) had a negative influence on outcome, but in multivariate analysis, monocytosis alone had a stronger association with poor OS.
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Affiliation(s)
- Alessia Bari
- Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy
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Batty N, Ghonimi E, Feng L, Fayad L, Younes A, Rodriguez MA, Romaguera JE, McLaughlin P, Samaniego F, Kwak LW, Hagemeister FB. The absolute monocyte and lymphocyte prognostic index for patients with diffuse large B-cell lymphoma who receive R-CHOP. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2012; 13:15-8. [PMID: 23137719 DOI: 10.1016/j.clml.2012.09.009] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2012] [Revised: 09/02/2012] [Accepted: 09/14/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND The baseline absolute monocyte count and absolute lymphocyte count were used to generate a prognostic index (the AMLPI) for survival in diffuse large B-cell lymphoma (DLBCL). METHODS Data from 245 patients with DLBCL who were treated with standard R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) were reviewed. By using the values previously reported for the AMLPI, its prognostic value was examined in our population. RESULTS After a median follow-up of 22 months for censored observations, the 3-year progression-free survival (PFS) rates for the international prognostic index (IPI) 0-2 and 3-5 risk groups were 73% and 58%, respectively (P = .0004); comparable overall survival (OS) rates were 88% and 68%, respectively (P < .0001). For patients with IPI scores of 0-2, 1-year PFS rates for AMLPI low-, intermediate-, and high-risk groups were 92%, 89%, and 80%, respectively (P = .022); comparable 1-year OS rates were 96%, 95%, and 80%, respectively (P = .049). By multivariate analysis, with the adjustment of IPI in the model, AMLPI effects (low- vs. high-risk groups) on PFS and OS rates were significant, with P = .046 (hazard ratio [HR] 0.402 [95% CI, 0.164-0.986] and P = .052 (HR 0.325 [95% CI, 0.104-1.011]), respectively. CONCLUSIONS The absolute monocyte and lymphocyte counts prognostic index (the AMLPI) may add prognostic value beyond that of the IPI for patients with DLBCL who receive R-CHOP.
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Affiliation(s)
- Nicolas Batty
- Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA
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Vari F, Gandhi MK. Back to basics: the complete blood cell count adds to the ability of immunohistochemistry in diffuse large B-cell lymphoma prognosis. Leuk Lymphoma 2012; 53:2097-8. [DOI: 10.3109/10428194.2012.701297] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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