TO DOSE OR NOT TO DOSE: ARE IL-10 AND IL-10:IL-6 RATIO ACCURATE BIOMARKERS TO DETECT LEPTOMENINGEAL INVOLVEMENT IN SMALL B-CELL LYMPHOPROLIFERATIONS?
(Abstract release date: 05/19/16)
EHA Library. Costopoulos M. 06/09/16; 134948; PB2048
Dr. Myrto Costopoulos
Contributions
Contributions
Abstract
Abstract: PB2048
Type: Publication Only
Background
Identifying the etiology of neurological symptoms in blood malignancies is still a challenging issue. Lymphomatous meningitis (LM) is mainly described in aggressive B-cell lymphomas (diffuse large B-cell (DLBCL) and Burkitt lymphomas). Leptomeningeal involvement in small B-cell lymphoproliferations is a rare, poorly described condition, mentioned only in a few case reports. The diagnosis is suspected in patients with non-specific central nervous system (CNS) symptoms and non-specific results on medical imaging. The diagnosis is confirmed by cytology (detection of tumor cells) in the cerebrospinal fluid (CSF). However, its sensitivity is low due to the scanty amounts of CSF and the rapid cell death. During the past decade, new complementary approaches have been proposed including flow cytometry (FCM) and quantifications of soluble biomarkers. More recently, interleukin-10 (IL-10) has been described as a candidate to diagnose primary central nervous system lymphoma (PCNSL) and systemic DLBCL with CNS involvement. Dosages can be processed using multiplex techniques with the possibility to undergo simultaneous multiple dosages on small volumes.
Aims
The aim of our study was to evaluate the diagnostic value of interleukin IL-10 and IL-6 quantifications combined with the IL-10:IL-6 ratio in CSF of patients suffering from LM secondary to systemic small B-cell lymphoproliferations.
Methods
We carried out a retrospective monocentric study over 4 years on 23 patients suffering from small B-cell LM: 5 chronic lymphocytic leukemias, 3 mantle-cell lymphomas, 13 Waldenström macroglobulinemias (WM) and 2 unclassified B-cell lymphomas. All patients presented CNS symptoms and documented LM (revealed either by cytology or FCM) at the diagnostic stage or before intrathecal chemotherapy. IL-10 and IL-6 quantifications were performed in CSF using the Cytometric Bead Array® technique (BD BiosciencesTM) on a FACSCanto II flow cytometer (BD BiosciencesTM), with a limit of detection of 2.5 pg/ml.
Results
As there is no well-defined IL-10 cutoff in the literature, we applied the IL-10:IL-6 ratio with a threshold set at 1 used to diagnose intra-ocular lymphoma. More than half of the patients (n=14) had an undetectable level of IL-10 along with low levels of IL-6, leading to an IL-10:IL-6 ratio <1 or undeterminable (group n°1). Patients in group n°2 also had ratios ≤1 but with detectable levels of IL-10. All patients with ratios≤1 (groups n°1 and 2) presented small B-cell lymphoproliferations with LM but no evidence of aggressive B-cell lymphoma. Patients in group n°3 had ratios >1. Two patients had PCNSL simultaneously diagnosed in the CSF and one patient had a WM transformed into DLBCL during follow-up. These 3 patients presented an increased IL-10 level (≥10 pg/ml). Thus, IL-10 and IL-10:IL-6 ratios in small B-cell lymphoproliferations unexpectedly differed from those observed in DLBCL. Our findings demonstrate the need of IL-10 and IL-6 quantification with the use of IL-10:IL-6 ratio in small B-cell lymphoproliferations to exclude any other aggressive B-cell malignancy. Interestingly, in WM patients with L, also called Bing Neel syndrome, IL-6 levels seemed higher (median: 10 pg/ml) than in other patients.
Conclusion
In conclusion, we describe for the first time that CSF IL-10 is not increased in small B-cell lymphoproliferations with LM. However, we report its usefulness in revealing more aggressive lymphomas in the context of either a transformation or when associated with another “hidden” lymphoma such as PCNSL. Supplementary data will be prospectively collected to confirm our results.
Session topic: E-poster
Type: Publication Only
Background
Identifying the etiology of neurological symptoms in blood malignancies is still a challenging issue. Lymphomatous meningitis (LM) is mainly described in aggressive B-cell lymphomas (diffuse large B-cell (DLBCL) and Burkitt lymphomas). Leptomeningeal involvement in small B-cell lymphoproliferations is a rare, poorly described condition, mentioned only in a few case reports. The diagnosis is suspected in patients with non-specific central nervous system (CNS) symptoms and non-specific results on medical imaging. The diagnosis is confirmed by cytology (detection of tumor cells) in the cerebrospinal fluid (CSF). However, its sensitivity is low due to the scanty amounts of CSF and the rapid cell death. During the past decade, new complementary approaches have been proposed including flow cytometry (FCM) and quantifications of soluble biomarkers. More recently, interleukin-10 (IL-10) has been described as a candidate to diagnose primary central nervous system lymphoma (PCNSL) and systemic DLBCL with CNS involvement. Dosages can be processed using multiplex techniques with the possibility to undergo simultaneous multiple dosages on small volumes.
Aims
The aim of our study was to evaluate the diagnostic value of interleukin IL-10 and IL-6 quantifications combined with the IL-10:IL-6 ratio in CSF of patients suffering from LM secondary to systemic small B-cell lymphoproliferations.
Methods
We carried out a retrospective monocentric study over 4 years on 23 patients suffering from small B-cell LM: 5 chronic lymphocytic leukemias, 3 mantle-cell lymphomas, 13 Waldenström macroglobulinemias (WM) and 2 unclassified B-cell lymphomas. All patients presented CNS symptoms and documented LM (revealed either by cytology or FCM) at the diagnostic stage or before intrathecal chemotherapy. IL-10 and IL-6 quantifications were performed in CSF using the Cytometric Bead Array® technique (BD BiosciencesTM) on a FACSCanto II flow cytometer (BD BiosciencesTM), with a limit of detection of 2.5 pg/ml.
Results
As there is no well-defined IL-10 cutoff in the literature, we applied the IL-10:IL-6 ratio with a threshold set at 1 used to diagnose intra-ocular lymphoma. More than half of the patients (n=14) had an undetectable level of IL-10 along with low levels of IL-6, leading to an IL-10:IL-6 ratio <1 or undeterminable (group n°1). Patients in group n°2 also had ratios ≤1 but with detectable levels of IL-10. All patients with ratios≤1 (groups n°1 and 2) presented small B-cell lymphoproliferations with LM but no evidence of aggressive B-cell lymphoma. Patients in group n°3 had ratios >1. Two patients had PCNSL simultaneously diagnosed in the CSF and one patient had a WM transformed into DLBCL during follow-up. These 3 patients presented an increased IL-10 level (≥10 pg/ml). Thus, IL-10 and IL-10:IL-6 ratios in small B-cell lymphoproliferations unexpectedly differed from those observed in DLBCL. Our findings demonstrate the need of IL-10 and IL-6 quantification with the use of IL-10:IL-6 ratio in small B-cell lymphoproliferations to exclude any other aggressive B-cell malignancy. Interestingly, in WM patients with L, also called Bing Neel syndrome, IL-6 levels seemed higher (median: 10 pg/ml) than in other patients.
Conclusion
In conclusion, we describe for the first time that CSF IL-10 is not increased in small B-cell lymphoproliferations with LM. However, we report its usefulness in revealing more aggressive lymphomas in the context of either a transformation or when associated with another “hidden” lymphoma such as PCNSL. Supplementary data will be prospectively collected to confirm our results.
Session topic: E-poster
Abstract: PB2048
Type: Publication Only
Background
Identifying the etiology of neurological symptoms in blood malignancies is still a challenging issue. Lymphomatous meningitis (LM) is mainly described in aggressive B-cell lymphomas (diffuse large B-cell (DLBCL) and Burkitt lymphomas). Leptomeningeal involvement in small B-cell lymphoproliferations is a rare, poorly described condition, mentioned only in a few case reports. The diagnosis is suspected in patients with non-specific central nervous system (CNS) symptoms and non-specific results on medical imaging. The diagnosis is confirmed by cytology (detection of tumor cells) in the cerebrospinal fluid (CSF). However, its sensitivity is low due to the scanty amounts of CSF and the rapid cell death. During the past decade, new complementary approaches have been proposed including flow cytometry (FCM) and quantifications of soluble biomarkers. More recently, interleukin-10 (IL-10) has been described as a candidate to diagnose primary central nervous system lymphoma (PCNSL) and systemic DLBCL with CNS involvement. Dosages can be processed using multiplex techniques with the possibility to undergo simultaneous multiple dosages on small volumes.
Aims
The aim of our study was to evaluate the diagnostic value of interleukin IL-10 and IL-6 quantifications combined with the IL-10:IL-6 ratio in CSF of patients suffering from LM secondary to systemic small B-cell lymphoproliferations.
Methods
We carried out a retrospective monocentric study over 4 years on 23 patients suffering from small B-cell LM: 5 chronic lymphocytic leukemias, 3 mantle-cell lymphomas, 13 Waldenström macroglobulinemias (WM) and 2 unclassified B-cell lymphomas. All patients presented CNS symptoms and documented LM (revealed either by cytology or FCM) at the diagnostic stage or before intrathecal chemotherapy. IL-10 and IL-6 quantifications were performed in CSF using the Cytometric Bead Array® technique (BD BiosciencesTM) on a FACSCanto II flow cytometer (BD BiosciencesTM), with a limit of detection of 2.5 pg/ml.
Results
As there is no well-defined IL-10 cutoff in the literature, we applied the IL-10:IL-6 ratio with a threshold set at 1 used to diagnose intra-ocular lymphoma. More than half of the patients (n=14) had an undetectable level of IL-10 along with low levels of IL-6, leading to an IL-10:IL-6 ratio <1 or undeterminable (group n°1). Patients in group n°2 also had ratios ≤1 but with detectable levels of IL-10. All patients with ratios≤1 (groups n°1 and 2) presented small B-cell lymphoproliferations with LM but no evidence of aggressive B-cell lymphoma. Patients in group n°3 had ratios >1. Two patients had PCNSL simultaneously diagnosed in the CSF and one patient had a WM transformed into DLBCL during follow-up. These 3 patients presented an increased IL-10 level (≥10 pg/ml). Thus, IL-10 and IL-10:IL-6 ratios in small B-cell lymphoproliferations unexpectedly differed from those observed in DLBCL. Our findings demonstrate the need of IL-10 and IL-6 quantification with the use of IL-10:IL-6 ratio in small B-cell lymphoproliferations to exclude any other aggressive B-cell malignancy. Interestingly, in WM patients with L, also called Bing Neel syndrome, IL-6 levels seemed higher (median: 10 pg/ml) than in other patients.
Conclusion
In conclusion, we describe for the first time that CSF IL-10 is not increased in small B-cell lymphoproliferations with LM. However, we report its usefulness in revealing more aggressive lymphomas in the context of either a transformation or when associated with another “hidden” lymphoma such as PCNSL. Supplementary data will be prospectively collected to confirm our results.
Session topic: E-poster
Type: Publication Only
Background
Identifying the etiology of neurological symptoms in blood malignancies is still a challenging issue. Lymphomatous meningitis (LM) is mainly described in aggressive B-cell lymphomas (diffuse large B-cell (DLBCL) and Burkitt lymphomas). Leptomeningeal involvement in small B-cell lymphoproliferations is a rare, poorly described condition, mentioned only in a few case reports. The diagnosis is suspected in patients with non-specific central nervous system (CNS) symptoms and non-specific results on medical imaging. The diagnosis is confirmed by cytology (detection of tumor cells) in the cerebrospinal fluid (CSF). However, its sensitivity is low due to the scanty amounts of CSF and the rapid cell death. During the past decade, new complementary approaches have been proposed including flow cytometry (FCM) and quantifications of soluble biomarkers. More recently, interleukin-10 (IL-10) has been described as a candidate to diagnose primary central nervous system lymphoma (PCNSL) and systemic DLBCL with CNS involvement. Dosages can be processed using multiplex techniques with the possibility to undergo simultaneous multiple dosages on small volumes.
Aims
The aim of our study was to evaluate the diagnostic value of interleukin IL-10 and IL-6 quantifications combined with the IL-10:IL-6 ratio in CSF of patients suffering from LM secondary to systemic small B-cell lymphoproliferations.
Methods
We carried out a retrospective monocentric study over 4 years on 23 patients suffering from small B-cell LM: 5 chronic lymphocytic leukemias, 3 mantle-cell lymphomas, 13 Waldenström macroglobulinemias (WM) and 2 unclassified B-cell lymphomas. All patients presented CNS symptoms and documented LM (revealed either by cytology or FCM) at the diagnostic stage or before intrathecal chemotherapy. IL-10 and IL-6 quantifications were performed in CSF using the Cytometric Bead Array® technique (BD BiosciencesTM) on a FACSCanto II flow cytometer (BD BiosciencesTM), with a limit of detection of 2.5 pg/ml.
Results
As there is no well-defined IL-10 cutoff in the literature, we applied the IL-10:IL-6 ratio with a threshold set at 1 used to diagnose intra-ocular lymphoma. More than half of the patients (n=14) had an undetectable level of IL-10 along with low levels of IL-6, leading to an IL-10:IL-6 ratio <1 or undeterminable (group n°1). Patients in group n°2 also had ratios ≤1 but with detectable levels of IL-10. All patients with ratios≤1 (groups n°1 and 2) presented small B-cell lymphoproliferations with LM but no evidence of aggressive B-cell lymphoma. Patients in group n°3 had ratios >1. Two patients had PCNSL simultaneously diagnosed in the CSF and one patient had a WM transformed into DLBCL during follow-up. These 3 patients presented an increased IL-10 level (≥10 pg/ml). Thus, IL-10 and IL-10:IL-6 ratios in small B-cell lymphoproliferations unexpectedly differed from those observed in DLBCL. Our findings demonstrate the need of IL-10 and IL-6 quantification with the use of IL-10:IL-6 ratio in small B-cell lymphoproliferations to exclude any other aggressive B-cell malignancy. Interestingly, in WM patients with L, also called Bing Neel syndrome, IL-6 levels seemed higher (median: 10 pg/ml) than in other patients.
Conclusion
In conclusion, we describe for the first time that CSF IL-10 is not increased in small B-cell lymphoproliferations with LM. However, we report its usefulness in revealing more aggressive lymphomas in the context of either a transformation or when associated with another “hidden” lymphoma such as PCNSL. Supplementary data will be prospectively collected to confirm our results.
Session topic: E-poster
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