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IMMUNOGLOBULIN HEAVY/LIGHT CHAIN ASSAY DETECT IMMUNE DYSREGULATION IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
Author(s):
Lee Magal
,
Lee Magal
Affiliations:
Almog Diagnostic,Park Shoham,Israel
Andrei Braester
,
Andrei Braester
Affiliations:
Hematology Unit,Galilee Medical Center,Naharia,Israel
Dali Najib
,
Dali Najib
Affiliations:
Hematology Unit,Ziv Medical Center,Zefat,Israel
Ariel Aviv
,
Ariel Aviv
Affiliations:
Hematology Unit,Haemek Medical Center,Afula,Israel
Yair Herishanu
,
Yair Herishanu
Affiliations:
Department of Hematology, Sourasky Medical Center,Tel Aviv, Israel
Mona Yuklea
,
Mona Yuklea
Affiliations:
Hematology Unit,Meir Medical Center,Kfar Saba,Israel
Lev Shvidel
,
Lev Shvidel
Affiliations:
Hematology Unit,Kaplan Medical Center, Rehovot,Israel
Naomi Rahimi-Levene
,
Naomi Rahimi-Levene
Affiliations:
Hematology Unit,Assaf Harofeh Medical Center, Zerifin,Israel
Rosa Ruchlemer
,
Rosa Ruchlemer
Affiliations:
Department of Hematology,Shaare Zedek Medical Center,Jerusalem,Israel
Ariela Arad
,
Ariela Arad
Affiliations:
Department of Hematology,Hadassah University Hospital,Jerusalem,Israel
Aaron Polliack
,
Aaron Polliack
Affiliations:
Department of Hematology,Hadassah University Hospital,Jerusalem,Israel
Tamar Tadmor
Tamar Tadmor
Affiliations:
Hematology Unit,Bnai-Zion Medical Center,Haifa,Israel
(Abstract release date: 05/18/17) EHA Library. Tadmor T. 05/18/17; 182503; PB1789
Dr. Tamar Tadmor
Dr. Tamar Tadmor
Contributions
PDF Abstract
Abstract

Abstract: PB1789

Type: Publication Only

Background
Chronic lymphocytic Leukemia (CLL) is frequently accompanied by immune dysregulation. Hypogammaglobulinemia is the most important associated immune defect and all three classes of immunoglobulins (IgG, A and M) are involved. Recently, a novel assay for detecting heavy/light chain (hevylight) and their ratios has been described (HLC), which improves immunoglobulin detection and monitoring in plasma-cell dyscrasias by quantitating the different light chain types of each immunoglobulin class.

The frequency and biological role of this assay has as yet not been studied in CLL.

Aims
To study the frequency of abnormal Heavy Light chain assay, in CLL patients.

Methods
This is an observational, multi-center study performed in collaboration with the Israeli CLL Study Group involving 10 medical centers in Israel.

The cohort included patients with CLL as well as healthy volunteers. All patients studied had complete clinical database available and all medical records were examined and then summarized.
Serum samples were analyzed for levels of: IgG1, IgG2, IgG3, IgG4.
Isoforms of heavy/light chain: IgG kappa, IgG lambda, IgA kappa, IgA lambda, IgM kappa, IgM lambda and Free light chain: kappa (K) and lambda (L), ratio of K/L and calculation of ratios of monoclonal/polyclonal immunoglobulin (HLC ratio).

Results

The total cohort consisted of 126 'treatment - naïve', patients with CLL and 26 healthy volunteers. Median age was 64 years, 64% were males and 78% had Binet stage A, while 19% and 3% were stages B or C respectively.
Significantly reduced levels of immunoglobulins associated with lambda chain
(IgG-L, IgA-L and IgM-L) were identified in CLL patients compared to healthy controls (p value of 0.001, 0.005 and 0.001 respectively).
Abnormal IgG-lambda values were evident in 15 patients (10%) and associated with more pronounced leucocytosis (p=0.005), higher B2mg levels (p=0.022) and the presence of 17p deletion (0.028). IgA and IgM lambda were abnormal in 38% and 56% of cases respectively compared to 8 and 9% in the controls.
For IgG subclasses: both IgG2 and IgG4 levels were significantly lower in CLL patients than in healthy controls (p= 0.001 and p<0.01 respectively). In addition, IgG2 and IgG4 were also confirmed to be significantly lower in CLL patients than in controls (p<0.001), while abnormal IgG2 levels were associated with more advanced Binet stage and elevated LDH levels.
Abnormal lambda FLC was observed 26 (21%) patients and only in one (4%) healthy control. Abnormal free light chain ratio (FLC) was present in 39 patients (32 %), with a mean value of 4.22 (0.11-62.15) while only 1 (4%) was observed in healthy controls (mean value of 1.76 (0.25-2.3)) and was also associated with more advanced Binet stage and elevated LDH (p=0.003.)

Conclusion
CLL cells may produce light chains, or as shown here abnormal intact immunoglobulins (heavy and light chains). HLC levels were associated with advanced stage and adverse prognostic parameters. These findings

lend support for the considerable potential of the HLC assay in the evaluation of clinical status in patients with CLL

Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Immune deficiency, Free light chain, Chronic Lymphocytic Leukemia

Abstract: PB1789

Type: Publication Only

Background
Chronic lymphocytic Leukemia (CLL) is frequently accompanied by immune dysregulation. Hypogammaglobulinemia is the most important associated immune defect and all three classes of immunoglobulins (IgG, A and M) are involved. Recently, a novel assay for detecting heavy/light chain (hevylight) and their ratios has been described (HLC), which improves immunoglobulin detection and monitoring in plasma-cell dyscrasias by quantitating the different light chain types of each immunoglobulin class.

The frequency and biological role of this assay has as yet not been studied in CLL.

Aims
To study the frequency of abnormal Heavy Light chain assay, in CLL patients.

Methods
This is an observational, multi-center study performed in collaboration with the Israeli CLL Study Group involving 10 medical centers in Israel.

The cohort included patients with CLL as well as healthy volunteers. All patients studied had complete clinical database available and all medical records were examined and then summarized.
Serum samples were analyzed for levels of: IgG1, IgG2, IgG3, IgG4.
Isoforms of heavy/light chain: IgG kappa, IgG lambda, IgA kappa, IgA lambda, IgM kappa, IgM lambda and Free light chain: kappa (K) and lambda (L), ratio of K/L and calculation of ratios of monoclonal/polyclonal immunoglobulin (HLC ratio).

Results

The total cohort consisted of 126 'treatment - naïve', patients with CLL and 26 healthy volunteers. Median age was 64 years, 64% were males and 78% had Binet stage A, while 19% and 3% were stages B or C respectively.
Significantly reduced levels of immunoglobulins associated with lambda chain
(IgG-L, IgA-L and IgM-L) were identified in CLL patients compared to healthy controls (p value of 0.001, 0.005 and 0.001 respectively).
Abnormal IgG-lambda values were evident in 15 patients (10%) and associated with more pronounced leucocytosis (p=0.005), higher B2mg levels (p=0.022) and the presence of 17p deletion (0.028). IgA and IgM lambda were abnormal in 38% and 56% of cases respectively compared to 8 and 9% in the controls.
For IgG subclasses: both IgG2 and IgG4 levels were significantly lower in CLL patients than in healthy controls (p= 0.001 and p<0.01 respectively). In addition, IgG2 and IgG4 were also confirmed to be significantly lower in CLL patients than in controls (p<0.001), while abnormal IgG2 levels were associated with more advanced Binet stage and elevated LDH levels.
Abnormal lambda FLC was observed 26 (21%) patients and only in one (4%) healthy control. Abnormal free light chain ratio (FLC) was present in 39 patients (32 %), with a mean value of 4.22 (0.11-62.15) while only 1 (4%) was observed in healthy controls (mean value of 1.76 (0.25-2.3)) and was also associated with more advanced Binet stage and elevated LDH (p=0.003.)

Conclusion
CLL cells may produce light chains, or as shown here abnormal intact immunoglobulins (heavy and light chains). HLC levels were associated with advanced stage and adverse prognostic parameters. These findings

lend support for the considerable potential of the HLC assay in the evaluation of clinical status in patients with CLL

Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Immune deficiency, Free light chain, Chronic Lymphocytic Leukemia

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