CORRELATION OF PRE-TREATMENT SERUM CYTOKINE ABNORMALITIES AND BLOOD MARKERS OF IMMUNOSUPPRESSION IN PATIENTS WITH LYMPHOMA
(Abstract release date: 05/19/16)
EHA Library. Binder M. 06/09/16; 132939; E1390
Disclosure(s): This work was supported by the Leukemia and Lymphoma Society Quest for Cures, the Predolin Foundation, and the University of Iowa / Mayo Clinic Lymphoma SPORE CA 97274.
Dr. Moritz Binder
Contributions
Contributions
Abstract
Abstract: E1390
Type: Eposter Presentation
Background
Multiple studies have demonstrated that higher ratios of pre-treatment absolute lymphocyte counts (ALC) and absolute monocyte counts (AMC) are associated with improved outcomes in non-Hodgkin (NHL) and Hodgkin lymphoma (HL). Conversely, elevated serum cytokines at diagnosis are associated with inferior outcomes. Lymphocytes and monocytes have been implicated in immune surveillance, suppression of host anti-tumor immunity, and alterations of the tumor microenvironment supporting growth and survival of lymphoma cells. The relationship between pre-treatment serum cytokines and ALC and AMC remains unknown. We hypothesized that patients with elevated serum cytokines would be more likely to have suppressed ALC/AMC ratios.
Aims
To evaluate the relationship between pre-treatment serum cytokines and ALC/AMC ratios in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), T-cell lymphoma (TCL), and HL.
Methods
We studied pre-treatment samples from 725 patients with lymphoma (DLBCL = 202, FL = 216, MCL = 88, TCL = 69, HL = 150) who enrolled in the University of Iowa / Mayo Clinic Lymphoma SPORE between 2002 and 2011 and were part of previous studies on cytokine secretion in lymphoma. Three-hundred seventy-six of these patients also had ALC/AMC ratios available, obtained from pre-treatment complete blood counts. Serum cytokine concentrations in patients and controls were measured using a standard ELISA (Invitrogen, Camarillo, CA) and analyzed using the Luminex-200 system. Data were acquired using STarStation software (Applied Cytometry, Dinnington, UK). Twelve cytokines passed quality control and were determined to have adequate measurements within the dynamic ranges of the assays: IL-1Ra, IL-2R, IL-8, IL-12p40p70 (IL-12), EGF, HGF, FGF-β, EOTAXIN, MIP-1β, MCP-1, IP-10, and MIG. The cytokines used for analysis were median-normalized to correct for plate effects. To assess the relationship between pre-treatment serum cytokines and ALC/AMC ratios, Spearman’s rank correlation coefficients were calculated. P-values below 0.001 were considered statistically significant.
Results
The median age at enrollment was 60 years (18 - 93), 407 patients (56%) were male. Ann Arbor stages were I-II (35%), III-IV (64%), or unknown (1%). Nineteen percent were experiencing B symptoms and 30% had bone marrow involvement. International prognostic index scores were 0-1 (49%), 2 (28%), 3 (16%), or 4-5 (6%). Table 1 shows the statistically significant correlations by lymphoma type.
Conclusion
Patients with NHL or HL with high pre-treatment serum cytokines tended to have lower ALC and higher AMC. Similar results were observed in all subsets except MCL. These data support the notion that high levels of serum cytokines are immunosuppressive and add to our understanding why the ALC/AMC ratio is of prognostic significance in lymphoma. It also provides further rationale to target immunosuppressive monocytes and the tumor microenvironment for therapeutic benefit.
Session topic: E-poster
Keyword(s): Cytokine, Hodgkin's lymphoma, Immunosuppression, Non-Hodgkin's lymphoma
Type: Eposter Presentation
Background
Multiple studies have demonstrated that higher ratios of pre-treatment absolute lymphocyte counts (ALC) and absolute monocyte counts (AMC) are associated with improved outcomes in non-Hodgkin (NHL) and Hodgkin lymphoma (HL). Conversely, elevated serum cytokines at diagnosis are associated with inferior outcomes. Lymphocytes and monocytes have been implicated in immune surveillance, suppression of host anti-tumor immunity, and alterations of the tumor microenvironment supporting growth and survival of lymphoma cells. The relationship between pre-treatment serum cytokines and ALC and AMC remains unknown. We hypothesized that patients with elevated serum cytokines would be more likely to have suppressed ALC/AMC ratios.
Aims
To evaluate the relationship between pre-treatment serum cytokines and ALC/AMC ratios in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), T-cell lymphoma (TCL), and HL.
Methods
We studied pre-treatment samples from 725 patients with lymphoma (DLBCL = 202, FL = 216, MCL = 88, TCL = 69, HL = 150) who enrolled in the University of Iowa / Mayo Clinic Lymphoma SPORE between 2002 and 2011 and were part of previous studies on cytokine secretion in lymphoma. Three-hundred seventy-six of these patients also had ALC/AMC ratios available, obtained from pre-treatment complete blood counts. Serum cytokine concentrations in patients and controls were measured using a standard ELISA (Invitrogen, Camarillo, CA) and analyzed using the Luminex-200 system. Data were acquired using STarStation software (Applied Cytometry, Dinnington, UK). Twelve cytokines passed quality control and were determined to have adequate measurements within the dynamic ranges of the assays: IL-1Ra, IL-2R, IL-8, IL-12p40p70 (IL-12), EGF, HGF, FGF-β, EOTAXIN, MIP-1β, MCP-1, IP-10, and MIG. The cytokines used for analysis were median-normalized to correct for plate effects. To assess the relationship between pre-treatment serum cytokines and ALC/AMC ratios, Spearman’s rank correlation coefficients were calculated. P-values below 0.001 were considered statistically significant.
Results
The median age at enrollment was 60 years (18 - 93), 407 patients (56%) were male. Ann Arbor stages were I-II (35%), III-IV (64%), or unknown (1%). Nineteen percent were experiencing B symptoms and 30% had bone marrow involvement. International prognostic index scores were 0-1 (49%), 2 (28%), 3 (16%), or 4-5 (6%). Table 1 shows the statistically significant correlations by lymphoma type.
| Table 1 Correlations between blood cytokines and ALC/AMC ratios by disease | ||||||
| All | DLBCL | FL | MCL | TCL | HL | |
| (n=376) | (n = 128) | (n = 101) | (n = 37) | (n = 37) | (n = 73) | |
| IL-2R | -0.37 * | -0.43 * | -0.33 * | -0.24 | -0.24 | -0.38 * |
| IP-10 | -0.21 * | -0.43 * | -0.17 | 0.10 | 0.01 | -0.18 |
| MIG | -0.30 * | -0.38 * | -0.22 | 0.03 | -0.41 | -0.38 |
| IL-12 | -0.16 | -0.17 | -0.23 | 0.06 | -0.53 * | -0.03 |
| Values denote Spearman’s rank correlation coefficients (* for p < 0.001) | ||||||
Conclusion
Patients with NHL or HL with high pre-treatment serum cytokines tended to have lower ALC and higher AMC. Similar results were observed in all subsets except MCL. These data support the notion that high levels of serum cytokines are immunosuppressive and add to our understanding why the ALC/AMC ratio is of prognostic significance in lymphoma. It also provides further rationale to target immunosuppressive monocytes and the tumor microenvironment for therapeutic benefit.
Session topic: E-poster
Keyword(s): Cytokine, Hodgkin's lymphoma, Immunosuppression, Non-Hodgkin's lymphoma
Abstract: E1390
Type: Eposter Presentation
Background
Multiple studies have demonstrated that higher ratios of pre-treatment absolute lymphocyte counts (ALC) and absolute monocyte counts (AMC) are associated with improved outcomes in non-Hodgkin (NHL) and Hodgkin lymphoma (HL). Conversely, elevated serum cytokines at diagnosis are associated with inferior outcomes. Lymphocytes and monocytes have been implicated in immune surveillance, suppression of host anti-tumor immunity, and alterations of the tumor microenvironment supporting growth and survival of lymphoma cells. The relationship between pre-treatment serum cytokines and ALC and AMC remains unknown. We hypothesized that patients with elevated serum cytokines would be more likely to have suppressed ALC/AMC ratios.
Aims
To evaluate the relationship between pre-treatment serum cytokines and ALC/AMC ratios in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), T-cell lymphoma (TCL), and HL.
Methods
We studied pre-treatment samples from 725 patients with lymphoma (DLBCL = 202, FL = 216, MCL = 88, TCL = 69, HL = 150) who enrolled in the University of Iowa / Mayo Clinic Lymphoma SPORE between 2002 and 2011 and were part of previous studies on cytokine secretion in lymphoma. Three-hundred seventy-six of these patients also had ALC/AMC ratios available, obtained from pre-treatment complete blood counts. Serum cytokine concentrations in patients and controls were measured using a standard ELISA (Invitrogen, Camarillo, CA) and analyzed using the Luminex-200 system. Data were acquired using STarStation software (Applied Cytometry, Dinnington, UK). Twelve cytokines passed quality control and were determined to have adequate measurements within the dynamic ranges of the assays: IL-1Ra, IL-2R, IL-8, IL-12p40p70 (IL-12), EGF, HGF, FGF-β, EOTAXIN, MIP-1β, MCP-1, IP-10, and MIG. The cytokines used for analysis were median-normalized to correct for plate effects. To assess the relationship between pre-treatment serum cytokines and ALC/AMC ratios, Spearman’s rank correlation coefficients were calculated. P-values below 0.001 were considered statistically significant.
Results
The median age at enrollment was 60 years (18 - 93), 407 patients (56%) were male. Ann Arbor stages were I-II (35%), III-IV (64%), or unknown (1%). Nineteen percent were experiencing B symptoms and 30% had bone marrow involvement. International prognostic index scores were 0-1 (49%), 2 (28%), 3 (16%), or 4-5 (6%). Table 1 shows the statistically significant correlations by lymphoma type.
Conclusion
Patients with NHL or HL with high pre-treatment serum cytokines tended to have lower ALC and higher AMC. Similar results were observed in all subsets except MCL. These data support the notion that high levels of serum cytokines are immunosuppressive and add to our understanding why the ALC/AMC ratio is of prognostic significance in lymphoma. It also provides further rationale to target immunosuppressive monocytes and the tumor microenvironment for therapeutic benefit.
Session topic: E-poster
Keyword(s): Cytokine, Hodgkin's lymphoma, Immunosuppression, Non-Hodgkin's lymphoma
Type: Eposter Presentation
Background
Multiple studies have demonstrated that higher ratios of pre-treatment absolute lymphocyte counts (ALC) and absolute monocyte counts (AMC) are associated with improved outcomes in non-Hodgkin (NHL) and Hodgkin lymphoma (HL). Conversely, elevated serum cytokines at diagnosis are associated with inferior outcomes. Lymphocytes and monocytes have been implicated in immune surveillance, suppression of host anti-tumor immunity, and alterations of the tumor microenvironment supporting growth and survival of lymphoma cells. The relationship between pre-treatment serum cytokines and ALC and AMC remains unknown. We hypothesized that patients with elevated serum cytokines would be more likely to have suppressed ALC/AMC ratios.
Aims
To evaluate the relationship between pre-treatment serum cytokines and ALC/AMC ratios in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), T-cell lymphoma (TCL), and HL.
Methods
We studied pre-treatment samples from 725 patients with lymphoma (DLBCL = 202, FL = 216, MCL = 88, TCL = 69, HL = 150) who enrolled in the University of Iowa / Mayo Clinic Lymphoma SPORE between 2002 and 2011 and were part of previous studies on cytokine secretion in lymphoma. Three-hundred seventy-six of these patients also had ALC/AMC ratios available, obtained from pre-treatment complete blood counts. Serum cytokine concentrations in patients and controls were measured using a standard ELISA (Invitrogen, Camarillo, CA) and analyzed using the Luminex-200 system. Data were acquired using STarStation software (Applied Cytometry, Dinnington, UK). Twelve cytokines passed quality control and were determined to have adequate measurements within the dynamic ranges of the assays: IL-1Ra, IL-2R, IL-8, IL-12p40p70 (IL-12), EGF, HGF, FGF-β, EOTAXIN, MIP-1β, MCP-1, IP-10, and MIG. The cytokines used for analysis were median-normalized to correct for plate effects. To assess the relationship between pre-treatment serum cytokines and ALC/AMC ratios, Spearman’s rank correlation coefficients were calculated. P-values below 0.001 were considered statistically significant.
Results
The median age at enrollment was 60 years (18 - 93), 407 patients (56%) were male. Ann Arbor stages were I-II (35%), III-IV (64%), or unknown (1%). Nineteen percent were experiencing B symptoms and 30% had bone marrow involvement. International prognostic index scores were 0-1 (49%), 2 (28%), 3 (16%), or 4-5 (6%). Table 1 shows the statistically significant correlations by lymphoma type.
| Table 1 Correlations between blood cytokines and ALC/AMC ratios by disease | ||||||
| All | DLBCL | FL | MCL | TCL | HL | |
| (n=376) | (n = 128) | (n = 101) | (n = 37) | (n = 37) | (n = 73) | |
| IL-2R | -0.37 * | -0.43 * | -0.33 * | -0.24 | -0.24 | -0.38 * |
| IP-10 | -0.21 * | -0.43 * | -0.17 | 0.10 | 0.01 | -0.18 |
| MIG | -0.30 * | -0.38 * | -0.22 | 0.03 | -0.41 | -0.38 |
| IL-12 | -0.16 | -0.17 | -0.23 | 0.06 | -0.53 * | -0.03 |
| Values denote Spearman’s rank correlation coefficients (* for p < 0.001) | ||||||
Conclusion
Patients with NHL or HL with high pre-treatment serum cytokines tended to have lower ALC and higher AMC. Similar results were observed in all subsets except MCL. These data support the notion that high levels of serum cytokines are immunosuppressive and add to our understanding why the ALC/AMC ratio is of prognostic significance in lymphoma. It also provides further rationale to target immunosuppressive monocytes and the tumor microenvironment for therapeutic benefit.
Session topic: E-poster
Keyword(s): Cytokine, Hodgkin's lymphoma, Immunosuppression, Non-Hodgkin's lymphoma
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