1.Serum beta-2 microglobulin in malignant lymphomas: an old but powerful prognostic factor.
Changhoon YOO ; Dok Hyun YOON ; Cheolwon SUH
Blood Research 2014;49(3):148-153
Beta-2 microglobulin is synthesized in all nucleated cells and forms the light chain subunit of the major histocompatibility complex class I antigen. Despite its potential role as a convenient and non-invasive prognostic indicator in malignant lymphomas, the influence of serum beta2 microglobulin is currently underestimated, and therapeutic decision making is rarely affected by this marker. Recent studies that included relatively large numbers of patients with specific histologic subtypes showed that serum beta2 microglobulin is a potent prognostic marker in malignant lymphomas. In follicular lymphoma, this effort led to the incorporation of serum beta2 microglobulin as an indicator in a new prognostic model. In this review, we summarize the current evidence supporting the role of serum beta2 microglobulin as a prognostic factor in patients with malignant lymphoma and discuss perspectives for future investigations.
Decision Making
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Humans
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Lymphoma*
;
Lymphoma, Follicular
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Major Histocompatibility Complex
2.Chimeric Antigen Receptor T-Cell Therapy for Diffuse Large B-Cell Lymphoma
Korean Journal of Medicine 2019;94(2):152-158
CD19 chimeric antigen receptor T-cell (CAR-T) therapy, a genetically engineered cell therapy, showed unprecedented efficacy in the treatment of relapsed or refractory diffuse large B-cell lymphoma. Two agents, axicabtagene ciloleucel and tisagenlecleucel, were approved by the Food and Drug Administration in 2017. However, CAR-T therapy is a treatment with complex logistics and high costs, as well as inherent adverse events, including cytokine-release syndrome and neurotoxicity. In addition, predictive biomarkers for efficacy and toxicity are lacking. Industry-academy cooperation is urgently required to develop CAR-T therapy that is effective, safe, and affordable for patients in Korea.
B-Lymphocytes
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Biomarkers
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Cell- and Tissue-Based Therapy
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Humans
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Korea
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Lymphoma, B-Cell
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Lymphoma, Large B-Cell, Diffuse
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Organization and Administration
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Receptors, Antigen
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T-Lymphocytes
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United States Food and Drug Administration
3.Chimeric Antigen Receptor T-Cell Therapy for Diffuse Large B-Cell Lymphoma
Korean Journal of Medicine 2019;94(2):152-158
CD19 chimeric antigen receptor T-cell (CAR-T) therapy, a genetically engineered cell therapy, showed unprecedented efficacy in the treatment of relapsed or refractory diffuse large B-cell lymphoma. Two agents, axicabtagene ciloleucel and tisagenlecleucel, were approved by the Food and Drug Administration in 2017. However, CAR-T therapy is a treatment with complex logistics and high costs, as well as inherent adverse events, including cytokine-release syndrome and neurotoxicity. In addition, predictive biomarkers for efficacy and toxicity are lacking. Industry-academy cooperation is urgently required to develop CAR-T therapy that is effective, safe, and affordable for patients in Korea.
4.Screening Tests for Early Diagnosis of Multiple Myeloma and Related Plasma Cell Disorders
Jin Seok KIM ; Sung-Soo YOON ; Chang-Ki MIN ; Je-Jung LEE ; Dok Hyun YOON ; Kihyun KIM
Korean Journal of Medicine 2021;96(5):371-381
Monoclonal gammopathy (MG) encompasses a diverse group of disorders characterized by the secretion of monoclonal immunoglobulins or their light-chain components. The incidence of multiple myeloma (MM) in South Korea is rapidly increasing, and it is important to be aware of its initial clinical presentations and the most efficient laboratory algorithms for early detection. Serum protein electrophoresis (SPE) and urine protein electrophoresis (UPE) are the primary screening tests for patients with clinically suspected MM or amyloid light-chain amyloidosis; these tests are reimbursed in South Korea. We reviewed clinical studies that applied national and international guidelines to evaluate test panels for early detection of MGs, including MM. The serum free light chain (sFLC) with SPE panel is recommended for the initial work up for diagnosis of MGs. In the case of a normal SPE, sFLC should be measured subsequently, so as not to miss the presence of M-protein. Use of this screening panel avoids medical expenses related to delayed diagnosis. Guidelines and recommendations suggest that no single method (SPE, serum immunofixation electrophoresis, sFLC, or UPE) should be used to exclude a diagnosis of MM. We believe that a screening test panel comprising SPE plus sFLC will increase the rate of early and accurate diagnosis of MM and related disorders.
5.Sequential heart and autologous stem cell transplantation for light-chain cardiac amyloidosis.
Jin Young HUH ; Seyoung SEO ; Cheolwon SUH ; Jooryung HUH ; Dok Hyun YOON ; Jae Joong KIM
Blood Research 2017;52(3):221-224
No abstract available.
Amyloidosis*
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Heart*
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Stem Cell Transplantation*
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Stem Cells*
6.EBV-positive diffuse large B-cell lymphoma of the elderly with aberrant expression of CD3 and TIA-1.
Miji LEE ; Hee Jeong CHA ; Dok Hyun YOON ; Cheolwon SUH ; Jooryung HUH
Blood Research 2013;48(2):156-160
No abstract available.
Aged
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B-Lymphocytes
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Humans
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Lymphoma, B-Cell
7.Prognostic value of immunohistochemical algorithms in gastrointestinal diffuse large B-cell lymphoma.
Hee Sang HWANG ; Dok Hyun YOON ; Cheolwon SUH ; Chan Sik PARK ; Jooryung HUH
Blood Research 2013;48(4):266-273
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous clinicopathological entity, and its molecular classification into germinal center B cell-like (GCB) and activated B cell-like (ABC) subtypes using gene expression profile analysis has been shown to have prognostic significance. Recent attempts have been made to find an association between immunohistochemical findings and molecular subgroup, although the clinical utility of immunohistochemical classification remains uncertain. METHODS: The clinicopathological features and follow-up data of 68 cases of surgically resected gastrointestinal DLBCL were analyzed. Using the immunohistochemical findings on tissue microarray, the cases were categorized into GCB and non-GCB subtypes according to the algorithms proposed by Hans, Muris, Choi, and Tally. RESULTS: The median patient age was 56 years (range, 26-77 years). Of the 68 cases included, 39.7% (27/68) involved the stomach, and 60.3% (41/68) involved the intestines. The GCB and non-GCB groups sorted according to Hans, Choi, and Tally algorithms, but not the Muris algorithm, were closely concordant (Hans vs. Choi, kappa=0.775, P<0.001; Hans vs. Tally, kappa=0.724, P<0.001; Choi vs. Tally, kappa=0.528, P<0.001). However, there was no prognostic difference between the GCB and non-GCB subtypes, regardless of the algorithm used. On univariate survival analyses, international prognostic index risk group and depth of tumor invasion both had prognostic significance. CONCLUSION: The Hans, Choi, and Tally algorithms might represent identical DLBCL subgroups, but this grouping did not correlate with prognosis. Further studies may delineate the association between immunohistochemical subgroups and prognosis.
B-Lymphocytes*
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Classification
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Follow-Up Studies
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Gastrointestinal Tract
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Germinal Center
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Humans
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Immunohistochemistry
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Intestines
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Lymphoma, B-Cell*
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Prognosis
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Stomach
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Transcriptome
8.Intestinal Diffuse Large B-Cell Lymphoma: An Evaluation of Different Staging Systems.
Hee Sang HWANG ; Dok Hyun YOON ; Cheolwon SUH ; Chan Sik PARK ; Jooryung HUH
Journal of Korean Medical Science 2014;29(1):53-60
The gastrointestinal tract is the most common primary extranodal site for diffuse large B-cell lymphoma (DLBCL). However, there is no consensus on the most appropriate staging system for intestinal DLBCL. We evaluated the utility of the modified Ann Arbor system, the Lugano system, and the Paris staging system (a modification of the Tumor, Node, Metastases [TNM] staging for epithelial tumors) in 66 cases of resected intestinal DLBCL. The cases were treated with surgery, plus either cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy alone (n=26) or with the addition of rituximab immunotherapy (n=40). Median follow-up time was 40.4 months (range, 2.1-171.6 months). Fifty-six patients (84.8%) achieved complete remission. The overall 5-yr survival rate was 86.4% (57/66). Of the stage categories defined for each staging system, only the T stage of the Paris classification showed prognostic significance for overall survival by univariate analysis. However, none of the stage parameters was significantly correlated with patient survival on multivariate analysis. In conclusion, the results suggest that the T stage of the Paris classification system may be a prognostic indicator in intestinal DLBCL. The results also imply that in surgically resected intestinal DLBCL, the addition of rituximab to the CHOP regimen does not confer significant survival advantage.
Adolescent
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Adult
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Aged
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Antibodies, Monoclonal, Murine-Derived/therapeutic use
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use
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Cyclophosphamide/therapeutic use
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Doxorubicin/therapeutic use
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Female
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Humans
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Immunologic Factors/therapeutic use
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Intestinal Neoplasms/*classification/drug therapy/mortality/surgery
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Lymphoma, Large B-Cell, Diffuse/*classification/drug therapy/mortality/surgery
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Male
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Middle Aged
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Neoplasm Staging/*methods
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Prednisone/therapeutic use
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Retrospective Studies
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Survival
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Survival Rate
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Treatment Outcome
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Vincristine/therapeutic use
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Young Adult
9.GLUT1 as a Prognostic Factor for Classical Hodgkin's Lymphoma: Correlation with PD-L1 and PD-L2 Expression.
Young Wha KOH ; Jae Ho HAN ; Seong Yong PARK ; Dok Hyun YOON ; Cheolwon SUH ; Jooryung HUH
Journal of Pathology and Translational Medicine 2017;51(2):152-158
BACKGROUND: Glucose transporter type 1 (GLUT1) expression is linked to glucose metabolism and tissue hypoxia. A recent study reported that GLUT1 was significantly associated with programmed death ligand 1 (PD-L1) as a therapeutic target in relapsed or refractory classical Hodgkin's lymphoma (cHL). The purpose of this study was to measure the expression of GLUT1 and assess its prognostic significance and potential relationships with PD-L1, programmed death ligand 2 (PD-L2), and programmed death-1 (PD-1) expressions in cHL. METHODS: Diagnostic tissues from 125 patients with cHL treated with doxorubicin, bleomycin, vinblastine, and dacarbazine were evaluated retrospectively via immunohistochemical analysis of GLUT1, PD-L1, PD-L2, and PD-1 expression. RESULTS: The median follow-up time was 4.83 years (range, 0.08 to 17.33 years). GLUT1, PD-L1, PD-L2, and PD-1 were expressed in 44.8%, 63.2%, 9.6%, and 13.6% of the specimens, respectively. Positive correlations were found between GLUT1 and PD-L1 expression (p = .004) and between GLUT1 and PD-L2 expression (p = .031). GLUT1 expression in Hodgkin/Reed-Sternberg (HRS) cells was not associated with overall survival or event-free survival (EFS) in the entire cohort (p = .299 and p = .143, respectively). A subgroup analysis according to the Ann Arbor stage illustrated that GLUT1 expression in HRS cells was associated with better EFS in advanced-stage disease (p = .029). A multivariate analysis identified GLUT1 as a marginally significant prognostic factor for EFS (p = .068). CONCLUSIONS: This study suggests that GLUT1 expression is associated with better clinical outcomes in advanced-stage cHL and is significantly associated with PD-L1 and PD-L2 expressions.
10.Prognostic Impact of Age at the Time of Diagnosis in Korean Patients with Diffuse Large B-cell Lymphoma in the Rituximab Era: A Single Institution Study
Hee Sang HWANG ; Meejeong KIM ; Chan-Sik PARK ; Dok Hyun YOON ; Cheolwon SUH ; Jooryung HUH ; Heounjeong GO
Cancer Research and Treatment 2021;53(1):270-278
Purpose:
In contrast to the Western diffuse large B-cell lymphoma (DLBCL), prognostic impact of age in a Korean population with DLBCL has not been fully evaluated.
Materials and Methods:
Six hundred and eight DLBCL patients treated with rituximab-containing chemotherapeutic regimens from January 2002 to March 2012 in Asan Medical Center were enrolled. Survival models using the restricted cubic spine−transformed age variable were constructed to evaluate non-linear relationships between age and survival outcome. Finally, age was categorized according to the conventional international prognostic index (IPI), National Comprehensive Cancer Network (NCCN)-IPI, and Grupo Español de Linfomas/Trasplante Autólogo de Médula Ósea (GELTAMO)-IPI schemes and the prognostic implications were evaluated.
Results:
The relative hazard did not change significantly during the first to fifth decades, but began to increase exponentially in patients aged over 62 years. This pattern or relationship was also retained in a multivariate model fitted to the age-adjusted IPI and relative dose intensity. Multivariate survival analysis revealed that age > 75 years, but not age > 60 years, was associated independently with poor overall and progression-free survival when the relative dose intensity and age-adjusted IPI were taken into account.
Conclusion
The outcome of DLBCL in Korean populations may deteriorate rapidly as age exceeds 62 years. Therefore, a consensus cutoff value for age in Korean DLBCL patients should be determined to better predict prognosis.