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Purpose@#Prognostic Index for Natural Killer Lymphoma (PINK) is the most widely accepted prognostic model for patients withextranodal natural killer/T-cell lymphoma (ENKTL) treated with non-anthracycline–based therapy. We aimed to evaluate the prognostic implications of serum β-2 microglobulin (β2M) in the context of PINK and proposed a new prognostic model. @*Materials and Methods@#A total of 138 patients who were newly diagnosed with ENKTL and treated with non-anthracycline-based chemotherapy were identified. The cut-off value of high serum β2M was calculated by maximal-chi square methods (4.1 mg/L). A new prognostic model incorporating serum β2M into PINK was proposed and validated in an independent validation cohort (n=88). @*Results@#The patients’ median age was 53.5 years (range, 19 to 80 years). Patients with high serum β2M levels had significantly worse overall survival (OS) and progression-free survival (PFS). In multivariate analysis, high serum β2M was an independent adverse prognostic factor for OS. A new PINK-B (Prognostic Index for Natural Killer Lymphoma-serum β-2 microglobulin) model stratifiedpatients into three groups with distinct OS and PFS in the training cohort (3-year OS, 84.1% [95% confidence interval, 75.1 to 94.2], 46.8% [36.1 to 60.8] and 17.6% [6.3 to 49.2] for the low-, intermediate, and high-risk groups, respectively; 3-year PFS, 70.6% [59.4 to 83.8], 35.9% [25.9 to 49.8], and 7.35% [1.1 to 46.7] for the low-, intermediate-, and high-risk groups, respectively). The PINK-B model was further validated in an independent cohort. @*Conclusion@#Serum β2M is an independent prognostic factor for ENKTL patients. The new serum β2M-based prognostic model may be useful for identifying ultra-high-risk patients, and it can easily be adopted into daily clinical practice.
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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.
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Background@#Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) in Western countries. However, it is relatively rare in Asia. This study examined epidemiologic characteristics of FL in South Korea, with an emphasis on recent trends of increase in cases. @*Methods@#We retrospectively examined 239 cases of newly diagnosed FL at a large tertiary institution in Korea (Asan Medical Center, Seoul, Republic of Korea) between 2008 and 2017. Age-adjusted incidence rates and clinicopathological variables were analyzed, and joinpoint regression analysis was used to identify the changes. @*Results@#The age-adjusted incidence of FL significantly increased during the study period (p = .034), and the ratio of (relative incidence) patients with FL to patients with NHL increased from 4.28% to 9.35% in the same period. Over the 10-year study assessment duration, the proportion of patients with stage III/IV FL (p = .035) and expression of BCL2 (p = .022) or BCL6 (p = .039) significantly increased. From 2013–2017, the proportion of patients with highrisk Follicular Lymphoma International Prognostic Index (FLIPI) score increased (21.5% to 28.7%), whereas that of low-risk FLIPI decreased (55.4% to 38.6%), although those results were not statistically significant (p = .066). @*Conclusions@#We found an increasing incidence of FL, with a disproportionate increase in the incidence of high-stage disease and recent changes in the clinicopathologic features of the Korean patient population.
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Purpose@#We aimed to investigate the prognostic value of serum β2-microglobulin for patients with Burkitt lymphoma (BL) and to propose a risk-stratifying classification system. @*Materials and Methods@#A prospective registry-based cohort study of BL patients treated with dose-intensive or effective dose-adjusted chemotherapies (n=81) was conducted. Survival outcomes were compared based on previously reported risk groups and/or serum β2-microglobulin levels. A risk-stratifying classification system incorporating serum β2-microglobulin levels was proposed and validated in an independent validation cohort (n=60). @*Results@#The median age was 47 years, and 57 patients (70.4%) were male. Patients with high serum β2-microglobulin levels (> 2 mg/L) had significantly worse progression-free survival (PFS) and overall survival (OS) (p 2 mg/L) was independently associated with a shorter PFS (hazards ratio [HR], 3.56; p=0.047) and OS (HR, 4.66; p=0.043). The new classification system incorporating the serum β2-microglobulin level allowed the stratification of patients into three distinct risk subgroups with 5-year OS rates of 100%, 89.5%, and 62.5%. In an independent cohort of BL, the system was validated by stratifying patients with different survival outcomes. @*Conclusion@#Serum β2-microglobulin level is an independent prognostic factor for BL patients. The proposed β2-microglobulin–based classification system could stratify patients with distinct survival outcomes, which may help define appropriate treatment approaches for individual patients.
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Background@#Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) in Western countries. However, it is relatively rare in Asia. This study examined epidemiologic characteristics of FL in South Korea, with an emphasis on recent trends of increase in cases. @*Methods@#We retrospectively examined 239 cases of newly diagnosed FL at a large tertiary institution in Korea (Asan Medical Center, Seoul, Republic of Korea) between 2008 and 2017. Age-adjusted incidence rates and clinicopathological variables were analyzed, and joinpoint regression analysis was used to identify the changes. @*Results@#The age-adjusted incidence of FL significantly increased during the study period (p = .034), and the ratio of (relative incidence) patients with FL to patients with NHL increased from 4.28% to 9.35% in the same period. Over the 10-year study assessment duration, the proportion of patients with stage III/IV FL (p = .035) and expression of BCL2 (p = .022) or BCL6 (p = .039) significantly increased. From 2013–2017, the proportion of patients with highrisk Follicular Lymphoma International Prognostic Index (FLIPI) score increased (21.5% to 28.7%), whereas that of low-risk FLIPI decreased (55.4% to 38.6%), although those results were not statistically significant (p = .066). @*Conclusions@#We found an increasing incidence of FL, with a disproportionate increase in the incidence of high-stage disease and recent changes in the clinicopathologic features of the Korean patient population.
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Purpose@#We aimed to investigate the prognostic value of serum β2-microglobulin for patients with Burkitt lymphoma (BL) and to propose a risk-stratifying classification system. @*Materials and Methods@#A prospective registry-based cohort study of BL patients treated with dose-intensive or effective dose-adjusted chemotherapies (n=81) was conducted. Survival outcomes were compared based on previously reported risk groups and/or serum β2-microglobulin levels. A risk-stratifying classification system incorporating serum β2-microglobulin levels was proposed and validated in an independent validation cohort (n=60). @*Results@#The median age was 47 years, and 57 patients (70.4%) were male. Patients with high serum β2-microglobulin levels (> 2 mg/L) had significantly worse progression-free survival (PFS) and overall survival (OS) (p 2 mg/L) was independently associated with a shorter PFS (hazards ratio [HR], 3.56; p=0.047) and OS (HR, 4.66; p=0.043). The new classification system incorporating the serum β2-microglobulin level allowed the stratification of patients into three distinct risk subgroups with 5-year OS rates of 100%, 89.5%, and 62.5%. In an independent cohort of BL, the system was validated by stratifying patients with different survival outcomes. @*Conclusion@#Serum β2-microglobulin level is an independent prognostic factor for BL patients. The proposed β2-microglobulin–based classification system could stratify patients with distinct survival outcomes, which may help define appropriate treatment approaches for individual patients.
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BACKGROUND: JL1, a CD43 epitope and mucin family cell surface glycoprotein, is expressed on leukemic cells. An anti-JL1 antibody combined with a toxic substance can have targeted therapeutic effects against JL1-positive leukemia; however, JL1 expression on bone marrow (BM) lymphoma cells has not been assessed using flow cytometry. We investigated JL1 expression on BM lymphoma cells from patients with non-Hodgkin lymphoma (NHL) to assess the potential of JL1 as a therapeutic target. METHODS: Patients with BM involvement of mature B-cell (N=44) or T- and natural killer (NK)-cell (N=4) lymphomas were enrolled from May 2015 to September 2016. JL1 expression on BM lymphoma cells was investigated using flow cytometry. Clinical, pathological, and cytogenetic characteristics, and treatment responses were compared according to JL1 expression status. RESULTS: Of the patients with NHL and BM involvement, 37.5% (18/48) were JL1-positive. Among mature B-cell lymphomas, 100%, 38.9%, 33.3%, 100%, and 25.0% of Burkitt lymphomas, diffuse large B-cell leukemias, mantle cell leukemias, Waldenstrom macroglobulinemia, and other B-cell lymphomas, respectively, were JL1-positive. Three mature T- and NK-cell NHLs were JL1-positive. JL1 expression was associated with age (P=0.045), complete response (P=0.004), and BM involvement at follow-up (P=0.017), but not with sex, performance status, the B symptoms, packed marrow pattern, cytogenetic abnormalities, or survival. CONCLUSIONS: JL1 positivity was associated with superior complete response and less BM involvement in NHL following chemotherapy.
Subject(s)
Humans , B-Lymphocytes , Bone Marrow , Burkitt Lymphoma , Chromosome Aberrations , Cytogenetics , Drug Therapy , Flow Cytometry , Follow-Up Studies , Leukemia , Leukemia, B-Cell , Lymphoma , Lymphoma, B-Cell , Lymphoma, Non-Hodgkin , Membrane Glycoproteins , Mucins , Therapeutic Uses , Waldenstrom MacroglobulinemiaABSTRACT
No abstract available.
Subject(s)
Culicidae , Hypersensitivity , Lymphohistiocytosis, Hemophagocytic , LymphomaABSTRACT
Purpose@#The treatment outcome of brentuximab vedotin (BV) has not been related with CD30 expressionin previous studies enrolling patients with a wide range of CD30 expression level.Thus, this study explored the efficacy of BV in high-CD30–expressing non-Hodgkin lymphoma(NHL) patients most likely to benefit. @*Materials and Methods@#This phase II study (Clinicaltrials.gov: NCT02280785) enrolled relapsed or refractory high-CD30–expressing NHL, with BV administered intravenously at 1.8 mg/kg every 3 weeks.The primary endpoint was > 40% disease control rate, consisting of complete response(CR), partial response (PR), or stable disease. We defined high CD30 expression as ! 30%tumor cells positive for CD30 by immunohistochemistry. @*Results@#High-CD30-expressing NHL patients (n=33) were enrolled except anaplastic large cell lymphoma.The disease control rate was 48.5% (16/33) including six CR and six PR; six patients(4CR, 2PR) maintained their response over 16 completed cycles. Response to BV and survivalwere not associated with CD30 expression levels. Over a median of 29.2 months offollow-up, the median progression-free and overall survival rates were 1.9 months and 6.1months, respectively. The most common adverse events were fever (39%), neutropenia(30%), fatigue (24%), and peripheral sensory neuropathy (27%). In a post-hoc analysis forthe association of multiple myeloma oncogene 1 (MUM1) on treatment outcome, MUM1-negative patients showed a higher response (55.6%, 5/9) than MUM1-positive patients(13.3%, 2/15). @*Conclusion@#BV performance as a single agent was acceptable in terms of disease control rates and toxicityprofiles, especially MUM1-negative patients.
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BACKGROUND: Single staining is commonly performed for practical pathologic diagnoses. However, this method is limited in its ability to specify cellular morphology and immunophenotype and often requires consumption of limited tissue. This study aimed to describe an optimized protocol for multiple in situ hybridization (ISH) and immunohistochemistry (IHC). METHODS: The quality of multistaining was evaluated by carefully changing each step of ISH and IHC in an angioimmunoblastic T-cell lymphoma (AITL) case on a Ventana BenchMark XT automated immunostainer. The optimized protocols were also performed using another immunostainer and in 15 cases of five Epstein-Barr virus (EBV)–associated malignancies using formalin-fixed paraffin-embedded tissue. RESULTS: The quality of various ISH-IHC staining protocols was semi-quantitatively evaluated. The best EBV-encoded RNA (EBER)-ISH/double IHC staining quality, equivalent to single staining, was obtained using the following considerations: initial EBER-ISH application, use of protease and antigen retrieval reagent (cell conditioning 1 [CC1] treatment time was minimized due to impact on tissue quality), additional baking/deparaffinization not needed, and reduced dilution ratio and increased reaction time for primary antibody compared with single immunostaining. Furthermore, shorter second CC1 treatment time yielded better results. Multiple staining was the best quality in another immunostainer and for different types of EBV-associated malignancies when it was performed in the same manner as for the Ventana BenchMark XT as determined for AITL. CONCLUSIONS: EBER-ISH and double IHC could be easily used in clinical practice with currently available automated immunostainers and adjustment of reagent treatment time, dilution ratio, and antibody reaction time.
Subject(s)
Benchmarking , Diagnosis , Herpesvirus 4, Human , Immunohistochemistry , In Situ Hybridization , Lymphoma, T-Cell , Methods , Reaction Time , RNAABSTRACT
Assessment of bone marrow (BM) involvement in peripheral T-cell lymphoma, not otherwise specified (PTCL) is straightforward in cases of extensive involvement but difficult in cases of minimal to partial involvement. We evaluated the usefulness of CD3 as an immunohistochemical marker for assessing BM involvement in PTCL patients. BM biopsies of 92 PTCL patients were immunohistochemically stained for CD3, CD4, CD8, CD20, and CD56, and evaluated by two hematopathologists. CD3 positivity was graded according to the proportion of CD3-positive cells and the number of CD3-positive cells in a cluster. These criteria were used to determine the cut-offs at which significant differences in progression-free survival (PFS) and overall survival (OS) were observed. Multivariate analysis controlling the International Prognostic Index (IPI) score and its individual factors revealed that >20 CD3-positive cells in a cluster adversely affected PFS (relative risk [RR], 2.1; 95% confidence interval [CI], 1.0–4.3; P=0.047) and OS (RR, 2.4; 95% CI, 1.1–5.1; P=0.028) independent of IPI score. A cluster with >20 CD3-positive cells is a candidate indicator for BM involvement in PTCL.
Subject(s)
Humans , Biopsy , Bone Marrow , Disease-Free Survival , Lymphoma, T-Cell, Peripheral , Multivariate AnalysisABSTRACT
BACKGROUND: The rectum is a relatively uncommon site for lymphoma compared with other gastrointestinal sites; no consensus regarding management of primary rectal lymphoma (PRL) has been formed due to its limited frequency. We aimed to investigate clinical characteristics and treatment outcomes in patients with PRL in a single center patient cohort. METHODS: We retrospectively analyzed the results of 16 consecutive patients with PRL, identified and treated at the Asan Medical Center, Seoul, Korea between January 1993 and December 2014. RESULTS: These 16 patients with PRL constituted 0.8% of all non-Hodgkin's lymphoma patients (N=1,984). B-cell lymphomas (N=14) made up the majority of the series, and half of these were extranodal marginal zone lymphomas (ENMZL, N=7). Ten patients received systemic chemotherapy with (N=3) or without rituximab (N=7), and 4 of these received additional local therapy. The others received radiotherapy (N=3) or endoscopic mucosal resection (N=3). Twelve patients (75%) achieved complete response (CR) after first-line treatment. Event-free survival (EFS) and overall survival (OS) in stages IE and IIE were significantly longer compared with stages IVE (P=0.001 and P=0.001, respectively). All patients with ENMZL (N=7) achieved CR during or after initial treatment. CONCLUSION: PRL is very rare and seems to present mostly as B-cell type. Stage is the most important prognostic factor, with significantly better survival associated with localized diseases. ENMZL may be one of the most common types of PRL with favorable treatment outcomes.
Subject(s)
Humans , B-Lymphocytes , Cohort Studies , Consensus , Disease-Free Survival , Drug Therapy , Korea , Lymphoma , Lymphoma, B-Cell , Lymphoma, Non-Hodgkin , Prognosis , Radiotherapy , Rectum , Retrospective Studies , Rituximab , SeoulABSTRACT
No abstract available.
Subject(s)
Heart Neoplasms , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Leukemia , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Recurrence , Stem Cell TransplantationABSTRACT
No abstract available.
Subject(s)
Amyloidosis , Heart , Stem Cell Transplantation , Stem CellsABSTRACT
Molecular pathologic testing plays an important role for the diagnosis, prognostication and decision of treatment strategy in lymphoproliferative disease. Here, we briefly review the molecular tests currently used for lymphoproliferative disease and those which will be implicated in clinical practice in the near future. Specifically, this guideline addresses the clonality test for B- and T-cell proliferative lesions, molecular cytogenetic tests for malignant lymphoma, determination of cell-of-origin in diffuse large B-cell lymphoma, and molecular genetic alterations incorporated in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Finally, a new perspective on the next-generation sequencing for diagnostic, prognostic, and therapeutic purpose in malignant lymphoma will be summarized.
Subject(s)
Classification , Cytogenetics , Diagnosis , In Situ Hybridization, Fluorescence , Lymphoma , Lymphoma, B-Cell , Lymphoproliferative Disorders , Molecular Biology , Pathology, Molecular , T-Lymphocytes , World Health OrganizationABSTRACT
Epstein-Barr virus (human herpesvirus-4) is very common virus that can be detected in more than 95% of the human population. Most people are asymptomatic and live their entire lives in a chronically infected state (IgG positive). However, in some populations, the Epstein-Barr virus (EBV) has been involved in the occurrence of a wide range of B-cell lymphoproliferative disorders (LPDs), including Burkitt lymphoma, classic Hodgkin’s lymphoma, and immune–deficiency associated LPDs (post-transplant and human immunodeficiency virus–associated LPDs). T-cell LPDs have been reported to be associated with EBV with a subset of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other rare histotypes. This article reviews the current evidence covering EBV-associated LPDs based on the 2016 classification of the World Health Organization. These LPD entities often pose diagnostic challenges, both clinically and pathologically, so it is important to understand their unique pathophysiology for correct diagnoses and optimal management.
Subject(s)
Humans , B-Lymphocytes , Burkitt Lymphoma , Classification , Diagnosis , Herpesvirus 4, Human , Lymphoma , Lymphoma, T-Cell , Lymphoma, T-Cell, Peripheral , Lymphoproliferative Disorders , T-Lymphocytes , World Health OrganizationABSTRACT
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.