The Ratio of the Absolute Lymphocyte Count to the Absolute Monocyte Count Is Associated with Prognosis in Hodgkin's Lymphoma: Correlation with Tumor‐Associated Macrophages

Abstract Background: EBV-positive diffuse large B-cell lymphoma (EBV+ DLBCL) of the elderly is a provisional entity included in the 2008 WHO Classification of Lymphomas. Diagnostic criteria include age >50 years, DLBCL morphology and EBV expression in lymphomatous cells. However, these criteria are evolving as several patients younger than 50 years of age without immunodeficiency have been diagnosed. Also, a specific cut-off for the percentage of EBV expression has not been defined. Lymphopenia, monocytosis, neutrophil-to-lymphocyte ratio (NLR) and the lymphocyte-to-monocyte ratio (LMR) have been reported prognostic in patients with DLBCL and other lymphomas. The goal of this retrospective study is to evaluate these novel prognostic factors in a cohort of EBV+ DLBCL patients. Methods: Between January 2002 and January 2014, all patients meeting criteria for EBV+ DLBCL were included in the analysis. Patients with evidence of immunosuppression were excluded. All cases were positive for the presence of EBV-encoded RNA (EBER) by in situ hybridization, and CD20 and/or PAX-5 expression by immunohistochemistry. Clinical and pathological data were reviewed retrospectively. Lymphopenia was defined as an absolute lymphocyte count <1000/uL, and monocytosis as an absolute monocyte count >600/uL. NLR was defined as the division of the absolute neutrophil count over the absolute lymphocyte count. LMR was defined as the division of the absolute lymphocyte count over the absolute monocyte count. Patient's biopsies were analyzed for the expression of BCL6, CD10, CD30 and MUM-1/IRF4. Overall survival (OS) curves were calculated using the Kaplan-Meier method, and compared using the log-rank test. Results: A total of 45 EBV+ DLBCL patients are included in this study. The median age was 68.9 years (range 25-95 years). Four patients (9%) were younger than 50 years. The male:female ratio was 2.2:1. B symptoms occurred in 60%, ECOG >1 in 55%, advanced stage (III/IV) in 58%, and elevated LDH levels in 44%. The International Prognostic Index (IPI) score was 0-2 in 39% and 3-5 in 61% of the patients. Lymphopenia was seen in 35%, and monocytosis in 69% of patients. Extranodal disease occurred in 23 patients (51%): stomach (n=3), tonsil (n=3), pleura (n=2), palate (n=2), cecum (n=2), bone marrow (n=2), ileum (n=1), bone (n=1), skin (n=1), lung (n=1), meninges (n=1), soft tisue (n=1) and peritoneum (n=1). Based on the Hans classification, 76% had non-germinal center origin. Ki67 expression was >80% in 53% of the patients. Chemotherapy was not received in 25% of the cases due to poor performance status. The Oyama score was: 0 factors (13%), 1 factor (47%), and 2 factors (40%) with 2-year OS of 86%, 49% and 27%, respectively (p=0.016). Lymphopenia was an adverse prognostic factor for OS (HR 3.23, 95% CI 1.24-8.43; p=0.017) in the univariate analysis. The 2-year OS for EBV+ DLBCL patients with lymphopenia was 24%, and 55% for patients without lymphopenia. Monocytosis, NLR and LMR were not significantly associated with OS in our cohort of EBV+ DLBCL patients. Conclusions: Lymphopenia, defined as an absolute lymphocyte count <1000/uL, appears as a prognostic factor for OS in EBV+ DLBCL. Disclosures No relevant conflicts of interest to declare.

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Time Interval from Last Chemotherapy to Stem Cell Collection Correlates with Peripheral Blood Absolute Lymphocyte Count at Apheresis and Survival Post-Autologous Stem Cell Transplantation in Non-Hodgkin’s Lymphoma.

Blood ◽

10.1182/blood.v104.11.2927.2927 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2927-2927 ◽

Cited By ~ 1

Author(s):

Shernan G. Holtan ◽

Luis F. Porrata ◽

David J. Inwards ◽

Stephen A. Ansell ◽

Ivana N.M. Micallef ◽

...

Keyword(s):

Stem Cell ◽

Peripheral Blood ◽

Lymphocyte Count ◽

Hodgkin’S Lymphoma ◽

Group Versus ◽

Absolute Lymphocyte Count ◽

Hodgkin's Lymphoma ◽

Time Interval ◽

Non Hodgkin's Lymphoma ◽

Stem Cell Collection

Abstract The infused autograft absolute lymphocyte count (A-ALC) is an independent prognostic factor for survival after autologous hematopoietic stem cell transplant (AHSCT) in non-Hodgkin’s lymphoma (NHL). Previous studies have shown that A-ALC directly correlates with the peripheral blood absolute lymphocyte count (PC-ALC) at the time of apheresis collection. However, factors affecting the PC-ALC at apheresis remain undefined. We hypothesized that one possible factor impacting PC-ALC may be the time interval from last chemotherapy to stem cell collection (TILC). Data from 160 patients who underwent AHSCT for treatment of relapsed NHL at Mayo Clinic between 1993 and 2001 were collected and analyzed. The primary end point of this study was correlation between TILC and PC-ALC, and our analysis revealed a strong correlation (r = 0.67, p < 0.0001). Further analysis revealed higher PC-ALC numbers in patients with TILC ≥ 60 days versus TILC < 60 days (median of 7.44 x 109/L in the ≥ 60 day group versus 3.87 x 109/L in the < 60 day group, p < 0.0001). Both the median overall survival (figure below) and the progression-free survival were longer in the TILC ≥ 60 days group versus the TILC < 60 days group (76 versus 21 months, p < 0.0037; 76 versus 11 months, p < 0.018, respectively). These findings were independent of other prognostic indicators for relapsed NHL patients undergoing APHSCT. The data supports our hypothesis that TILC affects PC-ALC and survival post-AHSCT in NHL. Figure Figure

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Lymphocyte:Monocyte Ratio At The Start Of Conditioning Regimen Is Associated With Survival Post-Autologous Stem Cell Transplantation (ASCT) For Lymphoma and Myeloma

Blood ◽

10.1182/blood.v122.21.3327.3327 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3327-3327

Author(s):

Guilherme Fleury Perini ◽

Alessandro de Moura Almeida ◽

Erika MM Costa ◽

Joyce E Hyppolito ◽

Fabio Rodrigues Kerbauy ◽

...

Keyword(s):

Stem Cell ◽

Lymphocyte Count ◽

Hodgkin’S Lymphoma ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

Conditioning Regimen ◽

Hodgkin's Lymphoma ◽

Prognostic Impact ◽

Monocyte Count ◽

Cox Analysis

Abstract Introduction Several studies have suggested that an increased peripheral blood absolute lymphocyte count (ALC) at day 15 after ASCT is associated with improved survival and decreased relapse rate. Recently, the ratio of ALC to the absolute monocyte count (AMC) (Lymphocyte:Monocyte Ratio; LMR) has been described as a strong prognostic factor at time of diagnosis in patients with various lymphoid malignancies. In most reports, a LMR cut-off value of less than 1.1 indicates patients who have a worse outcome. Objective To evaluate the prognostic impact of the LMR at start of conditioning regimen and at day 15 post ASCT in patients with a diagnosis of lymphoma and myeloma Methods We retrospectively reviewed the medical records of 121 adult patients with a diagnosis of lymphoma or myeloma who underwent ASCT at Hospital Israelita Albert Einstein from January, 2005 to July, 2012. Lymphocyte count was registered at the 15th day after SCT and lymphopenia was defined as an ALC< 500 at this time point. The LMR was calculated considering the ALC and AMC at baseline (start of conditioning regimen) and at day 15 post-ASCT. Overall survival (OS) was estimated from the time of transplant until death, with surviving patients censored at last follow-up. Variables entered into the multivariate Cox analysis were those with a p-value <0.10 in the univariate analysis. Statistical analysis was performed with STATA (v11.0) and alfa error was defined as 5%. Results The majority of patients were male (69%) and the median age was 58 years old (range: 3–76). Peripheral stem cell harvest was the main source of cells (61%). Diagnosis included multiple myeloma (49%), non-Hodgkin’s lymphoma (45%) and Hodgkin’s lymphoma (6%). The median LMR at start of conditioning regimen was 0.60, while at day 15 it was 1.75. Seventy-three percent of patients at start of conditioning had a LMR <1.1, while the same percentage at day 15 was 25%. Considering LMR cut-off at 1.1, an increased LMR value at baseline was associated with improved survival (HR 0.44; p=0.03), while it was not predictive at day 15 (HR=0.99; p=0.99). At 2 years, the OS was 48% for patients with a LMR<1.1 at start of conditioning regimen versus 76% for those patients with a LMR ≥1.1 (p=0.03 by logrank). In a multivariate Cox analysis considering age, sex, diagnosis, day 15 lymphopenia and baseline LMR, baseline LMR remained an independent variable associated with survival (HR=0.40, p=0.044), while day15 lymphopenia had no prognostic value (HR=0.80. p=0.56). Conclusion In our cohort of patients, the presence of an increased LMR at baseline before start of conditioning regimen identified a subgroup of patients who had a very good outcome. These results should be validated in other cohorts. Strategies to improve outcome for patients who present with decreased LMR and a better understanding of the role of LMR should be the focus of future studies. Disclosures: No relevant conflicts of interest to declare.

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A Quantitative Ultrastructural Study of Peripheral Blood Lymphocytes Containing Parallel Tubular Arrays in Epstein-Barr Virus and Cytomegalo-Virus Mononucleosis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100098769 ◽

1981 ◽

Vol 39 ◽

pp. 454-455

Author(s):

C. M. Payne ◽

P. M. Tennican

Keyword(s):

Peripheral Blood ◽

Lymphocyte Count ◽

Epstein Barr Virus ◽

Absolute Lymphocyte Count ◽

Peripheral Blood Lymphocytes ◽

Clinical State ◽

Barr Virus ◽

The Absolute ◽

Epstein Barr ◽

Tubular Arrays

In the normal peripheral circulation there exists a sub-population of lymphocytes which is ultrastructurally distinct. This lymphocyte is identified under the electron microscope by the presence of cytoplasmic microtubular-like inclusions called parallel tubular arrays (PTA) (Figure 1), and contains Fc-receptors for cytophilic antibody. In this study, lymphocytes containing PTA (PTA-lymphocytes) were quantitated from serial peripheral blood specimens obtained from two patients with Epstein -Barr Virus mononucleosis and two patients with cytomegalovirus mononucleosis. This data was then correlated with the clinical state of the patient.It was determined that both the percentage and absolute number of PTA- lymphocytes was highest during the acute phase of the illness. In follow-up specimens, three of the four patients' absolute lymphocyte count fell to within normal limits before the absolute PTA-lymphocyte count.In one patient who was followed for almost a year, the absolute PTA- lymphocyte count was consistently elevated (Figure 2). The estimation of absolute PTA-lymphocyte counts was determined to be valid after a morphometric analysis of the cellular areas occupied by PTA during the acute and convalescent phases of the disease revealed no statistical differences.

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Rapid Mobilization of CD34+ Cells Following Administration of the CXCR4 Antagonist AMD3100 to Patients With Multiple Myeloma and Non-Hodgkin's Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2004.07.131 ◽

2004 ◽

Vol 22 (6) ◽

pp. 1095-1102 ◽

Cited By ~ 318

Author(s):

Steven M. Devine ◽

Neal Flomenberg ◽

David H. Vesole ◽

Jane Liesveld ◽

Daniel Weisdorf ◽

...

Keyword(s):

Multiple Myeloma ◽

Hodgkin’S Lymphoma ◽

Hodgkin's Lymphoma ◽

Clinical Effects ◽

Cxcr4 Antagonist ◽

Cell Counts ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma ◽

Cd34 Cells ◽

The Absolute

PurposeInteractions between the chemokine receptor CXCR4 and its ligand stromal derived factor-1 regulate hematopoietic stem-cell trafficking. AMD3100 is a CXCR4 antagonist that induces rapid mobilization of CD34+ cells in healthy volunteers. We performed a phase I study assessing the safety and clinical effects of AMD3100 in patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL).Patients and MethodsThirteen patients (MM, n = 7; NHL, n = 6) received AMD3100 at a dose of either 160 μg/kg (n = 6) or 240 μg/kg (n = 7). WBC and peripheral blood (PB) CD34+ cell counts were analyzed at 4 and 6 hours following injection.ResultsAMD3100 caused a rapid and statistically significant increase in the total WBC and PB CD34+ counts at both 4 and 6 hours following a single injection. The absolute CD34+ cell count increased from a baseline of 2.6 ± 0.7/μL (mean ± SE) to 15.6 ± 3.9/μL and 16.2 ± 4.3/μL at 4 hours (P = .002) and 6 hours after injection (P = .003), respectively. The absolute CD34+ cell counts observed at 4 and 6 hours following AMD3100 were higher in the 240 μg/kg group (19.3 ± 6.9/μL and 20.4 ± 7.6/μL, respectively) compared with the 160 μg/kg group (11.3 ± 2.7/μL and 11.3 ± 2.5/μL, respectively). The drug was well tolerated and only grade 1 toxicities were encountered.ConclusionAMD3100 appears to be a safe and effective agent for the rapid mobilization of CD34+ cells in patients who have received prior chemotherapy. Further studies in combination with granulocyte colony-stimuating factor in patients with lymphoid malignancies are warranted.

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