This study provides an overview of the epidemiology and secular trends of malignant lymphoma in Japan. Using data from clinics and hospitals throughout Japan, we analyzed 9426 cases of malignant lymphoma diagnosed in 2007‐2014. We show that the proportion of follicular lymphoma and methotrexate‐associated lymphoproliferative disorder increased during this time, as did the onset age for follicular lymphoma and diffuse large B‐cell lymphoma. Significant increases in onset age for follicular lymphoma and diffuse large B‐cell lymphoma were observed in both men and women (all P values <0.0001 except for P = 0.0448 for the latter disease in women). Further studies are required to determine the reasons for the higher proportion of and onset age for these lymphomas. Additionally, we believe that continued observation of these trends is necessary.
Attenuated human leukocyte antigen (HLA) class I expression is implicated as a major immune escape mechanism in several types of tumor. We previously reported that HLA class I/β2 microglobulin and programmed death ligand-1 expression are prognostic factors in adult T-cell leukemia/lymphoma. A recent report suggested that HLA class II expression is also an important prognostic factor for the clinical outcome of programmed death-1 blockade therapy in recurrent/refractory Hodgkin lymphoma. This prompted us to evaluate HLA class II expression in adult T-cell leukemia/lymphoma and to compare the findings with the patients’ clinicopathological features. Of the 132 biopsy specimens examined from newly diagnosed patients, lymphoma cells were positive for HLA class II expression in 44 patients (33.3%), whereas programmed death ligand-1 expression was observed on neoplastic cells from nine patients (6.9%) and on stromal cells in the tumor microenvironment in 83 cases (62.9%). HLA class II-positive cases showed a significantly better overall survival compared to the HLA class II-negative cases ( P <0.0001). Patients positive for HLA class II and programmed death ligand-1 microenvironmental expression had significantly better prognosis than the other groups ( P <0.0001). HLA class II-positive and HLA class II-negative groups also showed a significant difference in complete remission rate ( P =0.0421), HLA class I/β2 microglobulin expression ( P =0.0165), and the number of programmed death-1-positive tumor infiltrating cells ( P =0.0020). HLA class II expression was a prognostic factor for overall survival both in univariate and multivariate analyses ( P <0.0001 and P =0.0007, respectively). Our study reveals that HLA class II is a novel prognostic factor in adult T-cell leukemia/lymphoma.
Histiocytic and dendritic cell neoplasms are rare and poorly studied. We report the clinical characteristics and prognostic factors in such cases in Japan. We investigated the clinical characteristics and survival in 87 adult patients with histiocytic and dendritic cell neoplasms. Fifty patients had histiocytic sarcoma, 12 had Langerhans cell histiocytosis, 11 had follicular dendritic cell sarcoma, 8 had Langerhans cell sarcoma, 6 had interdigitating cell sarcoma and 1 had indeterminate dendritic cell sarcoma. The median follow-up period was 18.0 (range: 9.6-71.8) months, and median overall survival (OS) was 23.5 months. The 2-year OS rate was 49.2%. In the multivariate analysis, elevated lactate dehydrogenase (LDH) (p =.004), ECOG performance status (PS) 2-4 (p =.006), and Ann Arbor stage III-IV (p =.008) affected OS. Stratification by elevated LDH, ECOG PS 2-4, and Ann Arbor stage III-IV allowed classification of patients into low risk, intermediate risk, and high risk groups. The same classification was applicable for HS and non-HS categories. In the rare neoplasms of histiocytic and dendritic cell sarcoma, ECOG PS, Ann Arbor stage, and LDH are important prognostic factors for predicting survival.
Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is a subtype of non-Hodgkin lymphoma with a poor prognosis. Although first-line treatments for patients with localized ENKTL have been established, there is no gold standard treatment for patients with advanced ENKTL and refractory and/or relapsed disease. Anti-CD30 antibody-based therapy, including brentuximab vedotin (BV), has been shown to target malignant lymphomas with CD30 expression. In particular, this therapeutic agent has recently been suggested to be effective for Hodgkin lymphoma and mature T-cell lymphoma. However, the efficacy of BV toward ENKTL has not yet been established. Therefore, we investigated the expression of CD30 in a large cohort to evaluate BV as a potential treatment for ENKTL. In this study, 97 Japanese patients with newly diagnosed ENKTL between January 2007 and December 2015 were enrolled. Flow cytometry and immunohistochemistry were performed for the evaluation of CD30 expression. If the cut-off value of CD30 expression is 1% or more, there were 55 positive cases (56.5%). According to the localization of lesion, the frequency of CD30 expression was significantly higher in the non-nasal type than in the nasal type (P = .0394). No differences were observed in almost all clinical characteristics between CD30-positive cases and CD30-negative cases. In addition, the expression of CD30 was not a prognostic factor for either overall survival or progression-free survival. In conclusion, frequent expression of CD30 in ENKTL suggests anti-CD30 antibody-based therapy may be an effective treatment.
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