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SERUM IL-10 LEVEL PREDICTS POOR PROGNOSIS IN PATIENTS WITH ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA: RESULTS OF A SINGLE CENTER COHORT STUDY
Author(s): ,
Seok Jin Kim
Affiliations:
Medicine,Samsung Medical Center,Seoul,Korea, Republic Of
,
Jun Soo Ham
Affiliations:
Samsung Medical Center,Seoul,Korea, Republic Of
,
Kyung Ju Ryu
Affiliations:
Samsung Biomedical Research Institute,Seoul,Korea, Republic Of
,
Young Hyeh Ko
Affiliations:
Pathology,Samsung Medical Center,Seoul,Korea, Republic Of
,
Won Seog Kim
Affiliations:
Medicine,Samsung Medical Center,Seoul,Korea, Republic Of
Sun-Hee Kim
Affiliations:
Laboratory Medicine,Samsung Medical Center,Seoul,Korea, Republic Of
(Abstract release date: 05/19/16) EHA Library. Kim S. 06/09/16; 132510; E961 Disclosure(s): There is no need to disclose actual financial value.
Prof. Seok Jin Kim
Prof. Seok Jin Kim
Contributions
Abstract
Abstract: E961

Type: Eposter Presentation

Background
Angioimmunoblastic T-cell lymphoma (AITL) is derived from T-follicular helper cell, and tumor cells are often outnumbered by admixed reactive inflammatory cells. Accordingly, the secretion of various cytokines and their interaction with tumor microenvironment has been more studied compared to other subtypes of PTCL. Interleukin-10 (IL-10) is one of T-helper cell-associated cytokine and promotes M2 macrophage inhibiting the anti-tumor action of non-neoplastic T-cells. Thus, serum IL-10 level might be associated with treatment outcome of AITL patients. 

Aims
The primary objective is to evaluate whether serum IL-10 level at diagnosis could predict survival outcome of AITL patients. The secondary objectives are the comparison of serum cytokine profiles according to subtypes of PTCL and their interaction with clinical and laboratory features.

Methods
Patients were from two prospective cohort studies of our institution: the first study (NCT#00822731) and the second study (NCT#01877109). Patients were diagnosed with AITL, peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), ALK-negative and positive anaplastic large cell lymphoma (ALCL) between September 2008 and December 2014 according to the pathology criteria of the World Health Organization. Serum samples at diagnosis after we obtained written informed consent were collected and stored at -80°C until analysis. Procarta cytokine profiling kit (Panomics, CA, USA) with Bio-Plex Cytokine Assay System (Bio-Rad Laboratories, Herucules, CA, USA) was used to measure different cytokines, including IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, and interferon-γ. Survival status and disease status were updated in February, 2016.

Results
A total of 97 patients were analyzed: AITL (n=37), PTCL-NOS (n=40), ALK-negative ALCL (n=11), and ALK-positive ALCL (n=9). All patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP-like regimens after diagnosis. The response to the first-line treatment was as follows: complete response (n=64), partial response (n=11), and progressive disease (n=22). With the median follow-up of 42 months, 58 patients experienced relapse, progression, or any kinds of death, and 44 patients died. The 3-year overall survival of AITL patients (66%) was superior to that of PTCL-NOS (43%) and inferior to ALK-positive ALCL (75%) in consistent with previous reports. Among measured cytokines, serum levels of IL-10 and IL-12 were significantly higher in AITL patients than other subtypes (P<0.05), and other cytokines did not show any significant association with subtypes. The cutoff for serum IL-10 and IL-12 was determined by the ROC curve, and high serum IL-10 (> 1.845 pg/mL) was significantly associated with poor overall survival (P=0.012, figure). All patients with high serum IL-10 showed disease progression after CHOP chemotherapy. This association was only found in AITL patients not other subtypes. In addition, other cytokines including IL-4,5, and 12 did not show a significant association with survival outcomes in AITL patients as well as other subtypes.

Conclusion
Serum IL-10 level at diagnosis might be a useful biomarker for predicting survival outcome in patients with AITL. Our findings should be confirmed by a future study with larger population.  



Session topic: E-poster

Keyword(s): Angioimmunoblastic T-cell lymphoma, IL-10, Prognosis
Abstract: E961

Type: Eposter Presentation

Background
Angioimmunoblastic T-cell lymphoma (AITL) is derived from T-follicular helper cell, and tumor cells are often outnumbered by admixed reactive inflammatory cells. Accordingly, the secretion of various cytokines and their interaction with tumor microenvironment has been more studied compared to other subtypes of PTCL. Interleukin-10 (IL-10) is one of T-helper cell-associated cytokine and promotes M2 macrophage inhibiting the anti-tumor action of non-neoplastic T-cells. Thus, serum IL-10 level might be associated with treatment outcome of AITL patients. 

Aims
The primary objective is to evaluate whether serum IL-10 level at diagnosis could predict survival outcome of AITL patients. The secondary objectives are the comparison of serum cytokine profiles according to subtypes of PTCL and their interaction with clinical and laboratory features.

Methods
Patients were from two prospective cohort studies of our institution: the first study (NCT#00822731) and the second study (NCT#01877109). Patients were diagnosed with AITL, peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), ALK-negative and positive anaplastic large cell lymphoma (ALCL) between September 2008 and December 2014 according to the pathology criteria of the World Health Organization. Serum samples at diagnosis after we obtained written informed consent were collected and stored at -80°C until analysis. Procarta cytokine profiling kit (Panomics, CA, USA) with Bio-Plex Cytokine Assay System (Bio-Rad Laboratories, Herucules, CA, USA) was used to measure different cytokines, including IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, and interferon-γ. Survival status and disease status were updated in February, 2016.

Results
A total of 97 patients were analyzed: AITL (n=37), PTCL-NOS (n=40), ALK-negative ALCL (n=11), and ALK-positive ALCL (n=9). All patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP-like regimens after diagnosis. The response to the first-line treatment was as follows: complete response (n=64), partial response (n=11), and progressive disease (n=22). With the median follow-up of 42 months, 58 patients experienced relapse, progression, or any kinds of death, and 44 patients died. The 3-year overall survival of AITL patients (66%) was superior to that of PTCL-NOS (43%) and inferior to ALK-positive ALCL (75%) in consistent with previous reports. Among measured cytokines, serum levels of IL-10 and IL-12 were significantly higher in AITL patients than other subtypes (P<0.05), and other cytokines did not show any significant association with subtypes. The cutoff for serum IL-10 and IL-12 was determined by the ROC curve, and high serum IL-10 (> 1.845 pg/mL) was significantly associated with poor overall survival (P=0.012, figure). All patients with high serum IL-10 showed disease progression after CHOP chemotherapy. This association was only found in AITL patients not other subtypes. In addition, other cytokines including IL-4,5, and 12 did not show a significant association with survival outcomes in AITL patients as well as other subtypes.

Conclusion
Serum IL-10 level at diagnosis might be a useful biomarker for predicting survival outcome in patients with AITL. Our findings should be confirmed by a future study with larger population.  



Session topic: E-poster

Keyword(s): Angioimmunoblastic T-cell lymphoma, IL-10, Prognosis

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