Purpose: Primary mediastinal large B-cell lymphoma (PMBCL) is a rare subtype of diffuse large B-cell lymphoma.Radiation therapy (RT) has served as the primary treatment option for PMBCL; however, its role has been questioned with the advent of intensified immunochemotherapy. This study aimed to investigate the role of consolidative RT in the primary treatment of PMBCL. Methods: This single-center retrospective study analyzed the survival outcomes of 65 patients newly diagnosed with PMBCL. The patients were divided into three treatment groups: (1) EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab), (2) R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), and (3) R-CHOP with consolidative RT. Results: The objective response and complete remission rates were 86.2% and 63.1%, respectively, with 3-year pro‑ gression-free survival (PFS) and overall survival (OS) rates of 72% and 81%, respectively. All patients in the R-CHOP + RT group achieved an objective response with better PFS) than those who did not receive consolidative RT (p = 0.028), although there was no significant difference in OS (p = 0.102). Consolidative RT benefited patients with an initially bulky disease or insufficient end-of-treatment response. The predictive value of  18 F-fluorodeoxyglucose positronemission tomography-computed tomography (PET-CT) in assessing the treatment response in PMBCL was revali‑ dated, showing that patients who achieved negative end-of-treatment PET-CT had significantly better survival outcomes than others. Conclusions R-CHOP is a useful alternative regimen when intensified chemotherapy is not feasible. Consolidative RT should be considered in cases with an initially bulky disease and insufficient end-of-treatment response.

Purpose: Primary mediastinal large B-cell lymphoma (PMBCL) is a rare subtype of diffuse large B-cell lymphoma.Radiation therapy (RT) has served as the primary treatment option for PMBCL; however, its role has been questioned with the advent of intensified immunochemotherapy. This study aimed to investigate the role of consolidative RT in the primary treatment of PMBCL. Methods: This single-center retrospective study analyzed the survival outcomes of 65 patients newly diagnosed with PMBCL. The patients were divided into three treatment groups: (1) EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab), (2) R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), and (3) R-CHOP with consolidative RT. Results: The objective response and complete remission rates were 86.2% and 63.1%, respectively, with 3-year pro‑ gression-free survival (PFS) and overall survival (OS) rates of 72% and 81%, respectively. All patients in the R-CHOP + RT group achieved an objective response with better PFS) than those who did not receive consolidative RT (p = 0.028), although there was no significant difference in OS (p = 0.102). Consolidative RT benefited patients with an initially bulky disease or insufficient end-of-treatment response. The predictive value of  18 F-fluorodeoxyglucose positronemission tomography-computed tomography (PET-CT) in assessing the treatment response in PMBCL was revali‑ dated, showing that patients who achieved negative end-of-treatment PET-CT had significantly better survival outcomes than others. Conclusions R-CHOP is a useful alternative regimen when intensified chemotherapy is not feasible. Consolidative RT should be considered in cases with an initially bulky disease and insufficient end-of-treatment response.

Purpose: Primary mediastinal large B-cell lymphoma (PMBCL) is a rare subtype of diffuse large B-cell lymphoma.Radiation therapy (RT) has served as the primary treatment option for PMBCL; however, its role has been questioned with the advent of intensified immunochemotherapy. This study aimed to investigate the role of consolidative RT in the primary treatment of PMBCL. Methods: This single-center retrospective study analyzed the survival outcomes of 65 patients newly diagnosed with PMBCL. The patients were divided into three treatment groups: (1) EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab), (2) R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), and (3) R-CHOP with consolidative RT. Results: The objective response and complete remission rates were 86.2% and 63.1%, respectively, with 3-year pro‑ gression-free survival (PFS) and overall survival (OS) rates of 72% and 81%, respectively. All patients in the R-CHOP + RT group achieved an objective response with better PFS) than those who did not receive consolidative RT (p = 0.028), although there was no significant difference in OS (p = 0.102). Consolidative RT benefited patients with an initially bulky disease or insufficient end-of-treatment response. The predictive value of  18 F-fluorodeoxyglucose positronemission tomography-computed tomography (PET-CT) in assessing the treatment response in PMBCL was revali‑ dated, showing that patients who achieved negative end-of-treatment PET-CT had significantly better survival outcomes than others. Conclusions R-CHOP is a useful alternative regimen when intensified chemotherapy is not feasible. Consolidative RT should be considered in cases with an initially bulky disease and insufficient end-of-treatment response.

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.

Purpose: Plasma circulating tumor DNA (ctDNA) could reflect the genetic alterations present in tumor tissues. However, there is little information about the clinical relevance of cell-free DNA genotyping in peripheral T-cell lymphoma (PTCL). Materials and Methods: After targeted sequencing plasma cell-free DNA of patients with various subtypes of PTCL (n=94), we analyzed the mutation profiles of plasma ctDNA samples and their predictive value of dynamic ctDNA monitoring for treatment outcomes. Results: Plasma ctDNA mutations were detected in 53 patients (56%, 53/94), and the detection rate of somatic mutations was highest in angioimmunoblastic T-cell lymphoma (24/31, 77%) and PTCL, not otherwise specified (18/29, 62.1%). Somatic mutations were detected in 51 of 66 genes that were sequenced, including the following top 10 ranked genes: RHOA, CREBBP, KMT2D, TP53, IDH2, ALK, MEF2B, SOCS1, CARD11, and KRAS. In the longitudinal assessment of ctDNA mutation, the difference in ctDNA mutation volume after treatment showed a significant correlation with disease relapse or progression. Thus, a ≥ 1.5-log decrease in genome equivalent (GE) between baseline and the end of treatment showed a significant association with better survival outcomes than a < 1.5-log decrease in GE. Conclusion Our results suggest the clinical relevance of plasma ctDNA analysis in patients with PTCL. However, our findings should be validated by a subsequent study with a larger study population and using a broader gene panel.

Background: While treatment strategies for mantle cell lymphoma (MCL) have evolved, patients often experience disease progression and require additional treatment therapies. Ibrutinib presents a promising option for relapsed or refractory MCL (RR-MCL). This study investigated real-world treatment outcomes of ibrutinib in patients with RR-MCL. Methods: A single-center retrospective analysis investigated clinical characteristics and survival outcomes of patients with RR-MCL, treated with ibrutinib. Results: Forty-two patients were included, with 16 received rituximab and bendamustine, and 26 receiving anthracycline-based regimens as front-line treatment. During a median follow-up of 46.0 months, the response rate to ibrutinib was 69%, with 12 CRs and 8 partial responses. Disease progression (54.8%) and adverse events (11.9%) were the primary reasons for discontinuation. Median progression-free survival (PFS) and overall survival (OS) were approximately 16.4 and 50.1 months, respectively. Patients older than 70 years (P =0.044 and P =0.006), those with splenomegaly (P =0.022 and P=0.006), and those with a high-risk simplified Mantle Cell Lymphoma International Prognostic Index (sMIPI) (P＜0.001 and P＜0.001) exhibited siginificantly inferior PFS and OS. Notably, patients with a high-risk sMIPI relapsed earlier. Post-ibrutinib treatment yilded an OS of 12.2 months, while clinical trial participants demonstrated superior survival compared to those receiving chemotherapy alone. Conclusion This study underscores the importance of considering patient characteristics before administering ibrutinib as salvage therapy. Early relapse was associated with poor outcomes, highlighting the need for novel therapeutic strategies.

Composite lymphoma is very rare and a combination of Hodgkin lymphoma and non-Hodgkin lymphoma and even histiocytic tumors can occur. Because of the unfamiliarity, not only can this cause diagnostic problems, but can also affect treatment plan. We report a case of composite lymphoma in a 40-year-old male. Initial biopsy showed a composite lymphoma of follicular lymphoma grade 1 and classic Hodgkin lymphoma. After chemotherapy, another lymph node was taken because of disease progression, which revealed follicular lymphoma, grade 3a without Hodgkin lymphoma component.

Purpose: Analysis of circulating tumor DNA (ctDNA) in blood could allow noninvasive genetic analysis of primary tumors. Although there have been unmet needs for noninvasive methods in patients with primary central nervous system lymphoma (PCNSL), it is still not determined whether plasma ctDNA analysis could be useful for patients with PCNSL. Materials and Methods: Targeted deep sequencing of 54 genes was performed in cell-free DNA isolated from plasma samples collected pretreatment, during treatment, and at the end of treatment in 42 consecutively diagnosed PCNSL patients between January 2017 and December 2018. Results: Targeted sequencing of plasma cell-free DNA detected somatic mutations representing ctDNA in 11 cases (11/41, 27%). The detection of ctDNA was not related to the concentration of cell-free DNA or tumor volume. The mutation profiles of these 11 cases varied between patients. The most frequently mutated gene was PIM1 (4/11, 36.4%), whereas KMT2D, PIK3CA, and MYD88 were each observed in three patients (3/11, 27%). The mutations of 13 genes were concordantly found in primary tumor tissue and plasma ctDNA, giving a detection sensitivity of 45%. During the serial tracking of seven patients with complete response, the disappearance of ctDNA mutations was found in four patients, whereas three patients had detected ctDNA mutation at the end of treatment. Conclusion The plasma ctDNA mutation analysis still has limited value for surveillance and predicting treatment outcomes of PCNSL because the detection efficiency was lower than other systemic lymphomas. Thus, analytical platforms should be improved to overcome anatomical hurdles associated with PCNSL.

Background/Aims: Waldenström macroglobulinemia (WM) is a rare lymphoproliferative disorder that usually follows an indolent clinical course. However, some patients show an aggressive clinical course leading to death. We explored the risk factors predicting poor prognosis in WM patients. Methods: We retrospectively analyzed 47 patients diagnosed with WM between 2000 and 2018 to explore risk factors predicting poor prognosis using various clinical and laboratory parameters and risk models including the International Prognostic Staging System for WM (IPSS-WM). Results: Over a median follow-up duration of 80.4 months, 29 patients died. The main causes of death were disease progression, organ failure related to amyloidosis, and infection. The median overall survival (OS) was 55.1 months, and 14 patients, including three with amyloidosis, died within 2 years. Serum β2-microglobulin level higher than 4 mg/dL was significantly associated with poor OS. Accordingly, the IPSS-WM showed a significant association with poor prognosis compared with other risk models, and the low-risk group had better OS than intermediate- and high-risk groups. In the retrospective analysis using the results of targeted sequencing in two cases representing good and bad prognosis, different patterns of mutation profiles were observed, including mutations of MYD88, TP53, ARID1A, and JAK2 in a refractory case. Conclusions Serum β2-microglobulin could be a single biomarker strongly predictive of poor survival of WM patients, and the low-risk group of the IPSS-WM risk model including serum β2-microglobulin has better prognostic value than other risk models. Mutation analysis also might provide additional information to predict high-risk patients.

Background: Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is rare Epstein-Barr virus (EBV)-associated disease. The classic form of HVLPD is a self-resolving disease, whereas the systemic form can progress to malignant lymphoma, resulting in fatal outcomes. However, the prognostic factors remain unclear. Objective: This study aimed to evaluate the clinical characteristics of HVLPD and the association between whole blood EBV DNA and clinical outcomes. Methods: We retrospectively reviewed our 25-year experience involving 11 patients with HVLPD from a single tertiary center in South Korea and evaluated the clinical characteristics of HVLPD and the correlation between whole blood EBV DNA and clinical outcomes. Results: Of the total 11 patients, 54.5% (6/11) manifested classic HVLPD that resolved with conservative treatment, while 45.5% (5/11) patients had systemic HVLPD, four of whom died of progressive disease or hemophagocytic syndrome. Five patients with systemic HVLPD manifested severe skin lesions such as prominent facial edema, deep ulcers and necrotic skin lesions involving sun-protected areas. Median EBV DNA levels at initial diagnosis were higher in three dead patients than in those alive (2,290 vs. 186.62 copies/μl). Conclusion When EBV DNA levels were high, patients showed severe skin lesions and when EBV DNA levels were low, skin lesions tended to improve. Thus, patients with high EBV DNA levels showed an increased risk of severe skin lesions and disease progression.