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Aims: The Lugano classification is a novel staging system for lymphomas established in 2014. In this staging system, 18F‐fluorodeoxyglucose‐positron emission tomography/computed tomography (FDG‐PET/CT) was formally incorporated into standard staging for FDG‐avid lymphomas, including Hodgkin lymphoma (HL). We retrospectively analyzed patients with HL who were newly diagnosed and treated at our institution to evaluate the utility of the Lugano classification compared to the Ann Arbor classification in Japanese patients with this type of lymphoma. Methods: Patients newly diagnosed with HL between 2005 and 2011 were identified through our departmental database. Data from neck‐chest‐abdomen‐pelvis CT scans, BM examinations, and FDG‐PET/CT that were routinely performed for staging at our clinical practice were retrieved and analyzed. Results: Fifty‐four patients with a median age of 35.5 years (range: 15‐78 years) were investigated in this retrospective study. The Lugano stage matched the Ann Arbor stage in 46 patients (85%). Six patients (11%) were upstaged while two (4%) were downstaged per the Lugano classification. Four patients (7%) were converted from early stage to advanced stage, but none was converted in the reverse. Among 11 patients (20%) with PET‐positive bone/bone marrow lesions, only one (2%) exhibited biopsy‐proven bone marrow involvement of HL cells. Conclusion: Our data revealed a high concordance rate between the Lugano and Ann Arbor staging system in Japanese patients with HL. Because of its low diagnostic value, routine bone marrow examination might be unnecessary for staging when FDG‐PET/CT is used as a substitute. [ABSTRACT FROM AUTHOR]

Classical Hodgkin lymphoma (cHL) is a B-cell-derived lymphoid malignancy with the most favorable prognosis among various adult malignancies. However, once it becomes refractory disease to chemotherapy or relapses after high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT), it is difficult to manage with conventional cytotoxic chemotherapy. The introduction of brentuximab vedotin (BV) has changed the treatment landscape of cHL in the past decade. Several studies demonstrated high efficacy of BV monotherapy in heavily treated patients with cHL relapsed or refractory after HDC/ASCT. Recent studies also reported high efficacy of concurrent or sequential combination of BV and chemotherapy in patients with transplant-eligible relapsed/refractory cHL at the second-line setting. In addition, a randomized phase III trial ECHELON-1 reported a positive result of BV in combination with AVD (doxorubicin, vinblastine, and dacarbazine) in patients with newly diagnosed advanced-stage cHL. In this review, we summarize available data of BV for cHL and discuss the current and future role of BV in the management of cHL. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: We aimed at investigating the relationship between classical Hodgkin lymphoma (cHL), primary mediastinal large B‐cell lymphoma (PMBL), and gray zone lymphoma (GZL) with intermediate characteristics between cHL and PMBL, from the perspective of the aberration in programed cell death 1 and the programed death ligands (PDLs) network. Methods: We explored the expression levels of PDLs and chromosomal anomalies in 67 cases: 34 cases with cHL, 20 with PMBL, and 13 with GZL, using immunohistochemical analyses and Fluorescence In Situ Hybridization (FISH). Results: Twenty‐one cHL (62%), 3 PMBL (15%), and 6 GZL (46%) cases showed staining to PD‐L1 antibodies in more than 70% of tumor cells. Two cHL (6%), 10 PMBL (50%), and 3 GZL (23%) cases were not stained by PD‐L1 antibodies. Patients over 40 years old manifest more frequent expression of PD‐L1 in cHL. Proportion of tumors stained by PD‐L2 antibody was increased in PMBL. FISH analyses with a PD‐L1/PD‐L2 probe detected 5 amplification, 1 gain, and 7 polysomy cases in cHL, 1 amplification and 1 polysomy case in GZL, and amplification in 1 PMBL case. Conclusion: We identified increased staining of PD‐L1 in cHL and that of PD‐L2 in PMBL. GZL had a pattern similar to that of cHL. [ABSTRACT FROM AUTHOR]

Hodgkin lymphoma (HL) is a rare subtype of malignant lymphoma in Japan, and there are few reports of HL in Japan in recent years. We retrospectively analyzed the clinical features of 139 patients with HL who were diagnosed and treated at our institution between 1997 and 2011. The median age at diagnosis was 34 years with 83 male. Of these patients, 83 (60 %) were early stage and 56 (40 %) were advanced-stage. Seventy-three patients (88 %) with early stage disease received ABVd followed by irradiation. All of the 56 advanced-stage patients received chemotherapy, mainly ABVd. The 5-year progression-free survival (PFS) rates and overall survival rates were 90 and 94 % in patients with early stage disease, and 71 and 90 % in those with advanced-stage disease. The PFS of patients with advanced-stage disease was significantly lower than those with early stage (p = 0.014). In conclusion, the outcomes of Japanese patients with HL in recent years were not improved as compared with the results of previous reports. We confirmed that patients with advanced-stage disease have lower PFS than those with early stage disease. Prospective studies are needed to establish novel treatment strategies to improve the outcome of HL patients, especially those with advanced disease. [ABSTRACT FROM AUTHOR]

Detection of immunoglobulin light chain restriction (LCR) by flow cytometry (FCM) is a useful tool for B-cell non-Hodgkin lymphoma (B-NHL) diagnosis. Here, we identified B-NHLs without LCR by FCM and investigated the pathological causes for lack of LCR. A total of 89/471 cases (19%) of B-NHL were LCR-negative. The incidence of lack of LCR was 30% both in diffuse large B-cell lymphoma (DLBCL) and marginal zone lymphoma (MZL), and was 6% in follicular lymphoma (FL). In DLBCL cases, low expression of surface membrane light chain (33%), low proportion of lymphoma cells (11%), CD45 negativity (9%), and destruction or sampling error were suggested as reasons for lack of LCR. In MZL cases, the low proportion of lymphoma cells owing to admixture of many reactive germinal centres, and non-detection of plasmacytoid lymphoma cells by CD45 gating might be the reasons. Based on pathological subtypes, the frequency and reasons for lack of LCR by FCM varied. [ABSTRACT FROM AUTHOR]

Background: The TNFAIP3 gene, which encodes a ubiquitin-modifying enzyme (A20) involved in the negative regulation of NF-κB signaling, is frequently inactivated by gene deletions/mutations in a variety of B-cell malignancies. However, the detection of this in primary Hodgkin lymphoma (HL) specimens is hampered by the scarcity of Hodgkin Reed-Sternberg (HR-S) cells even after enrichment by micro-dissection. Methods: We used anti-CD30 immunofluorescence with fluorescence in-situ hybridization (FISH) to evaluate the relative number of TNFAIP3/CEP6 double-positive signals in CD30-positive cells. Results: From a total of 47 primary classical Hodgkin lymphoma (cHL) specimens, 44 were evaluable. We found that the relative numbers of TNFAIP3/CD30 cells were distributed among three groups, corresponding to those having homozygous (11%), heterozygous (32%), and no (57%) deletions in TNFAIP3. This shows that TNFAIP3 deletions could be sensitively detected using our chosen methods. Conclusions: Comparing the results with mutation analysis, TNFAIP3 inactivation was shown to have escaped detection in many samples with homozygous deletions. This suggests that TNFAIP3 inactivation in primary cHL specimens might be more frequent than previously reported. [ABSTRACT FROM AUTHOR]

An increasing incidence of Pneumocystis jiroveci pneumonia (PCP) in patients with B-cell non-Hodgkin lymphoma (B-NHL) receiving rituximab treatment has been reported. We reviewed patients with B-NHL who underwent chemotherapy from 2004 to 2008 at our institution to identify risk factors for PCP development during and after chemotherapy. Among 297 patients with B-NHL, six developed PCP. Of 121 patients (41%) who received PCP prophylaxis with sulfamethoxazole-trimethoprim during chemotherapy, none developed PCP (0%), while among 176 patients (59%) who had no prophylaxis, six (3.4%) developed PCP at a median of 2 months (range: 1-3 months) after starting chemotherapy. Patients with CD4+ lymphocyte counts ≤200/mm3 before chemotherapy had a higher risk of developing PCP ( p = 0.045), while a history of rituximab treatment was not related to PCP. CD4+ lymphocyte counts ≤200/mm3 during and after chemotherapy were observed in 18.9% of patients. [ABSTRACT FROM AUTHOR]

Although Hodgkin lymphoma has become one of the most curable lymphomas, 20-30% of patients still relapse after first-line treatment. In relapsed patients, high dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT) is a standard treatment approach, however transplant-ineligible patients or patients who relapse after HDC/ASCT still have a rather poor prognosis. Immuno-checkpoint inhibitors are one of the most promising cancer immunotherapies in various advanced cancers including hematologic malignancies. PD-1-blocking antibodies have been used to enhance immunity in several malignancies and obtain durable responses, especially in the patients with heavily treated relapsed/refractory Hodgkin lymphoma. Nowadays, several clinical trials including single agent or combination therapies for Hodgkin lymphoma have been developed or are currently under investigation. The results of ongoing and future clinical trials may establish new treatment paradigm in Hodgkin lymphoma. [ABSTRACT FROM AUTHOR]