Prognostic impact of interim positron emission tomography in mantle cell lymphoma patients treated with frontline R-CHOP.

Although 18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG PET) is commonly used for initial staging and therapeutic response evaluation in aggressive lymphomas, its prognostic utility for mantle cell lymphoma (MCL) is controversial. Therefore, we retrospectively evaluated the correlations of interim PET (iPET) and end-of-treatment PET (ePET) response with survival outcomes in 89 consecutive advanced MCL patients treated with frontline R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone). iPET positivity was strongly associated with inferior five-year overall survival (OS) [hazard ratio (HR) 7·84, P < 0·0001] and poor five-year progression-free survival (PFS) (HR 3·34, P < 0·0001). OS and PFS were more favourable in the order early metabolic responder (iPETneg  â†’ ePETneg ), delayed responder (iPETpos  â†’ ePETneg ), loss-metabolic responder (iPETneg  â†’ ePETpos ), and never-metabolic responder (iPETpos  â†’ ePETpos ). In the autologous haematopoietic stem cell transplantation (auto-HSCT)-fit subgroup, OS was more favourable in the order early metabolic responders, delayed metabolic responders, and non-metabolic responders, with a marginal trend toward statistical significance (HR 3·41, P = 0·051), and PFS was significantly superior in early metabolic responders (HR 4·43, P = 0·002). In a group that was ineligible for auto-HSCT, OS and PFS were significantly superior in early metabolic responders. Our results suggested that iPET is of prognostic value and an independent predictor of survival in MCL patients receiving frontline R-CHOP. Therefore, prospective clinical trials of iPET-guided treatment strategies for these patients are warranted.

Pilot study of pegylated interferon alpha-2a treatment during chemo- and radiotherapy and post-remission maintenance in patients with EBV-positive extranodal NK/T cell lymphoma.

The role of the Epstein­Barr virus (EBV) in the pathogenesis of extranodal natural killer/T-cell lymphoma (ENKTCL), and its resistance to chemotherapy raises the possibility of antiviral therapeutic strategies. The aim of this prospective pilot study was to evaluate the feasibility and effectiveness of antiviral treatment using pegylated interferon alpha-2a (pIFN α-2a) as an adjunct to induction and maintenance therapy in patients with ENKTCL. A total of seven patients with newly diagnosed EBV-positive ENKTCL were enrolled. Pegylated IFN α-2a was administered during induction chemoradiotherapy. If patients achieved a partial or complete response (PR or CR, respectively), high-dose chemotherapy with autologous stem cell transplantation (HDT/SCT) was given. After transplantation, maintenance therapy included pIFN α-2a for 3 years. Of the patients available for evaluation, all achieved a CR or PR after induction therapy but one patient relapsed before HDT/SCT. The event free survival and overall survival at 3 years were 50.0 ± 20.4% and 66.7 ± 19.2%, respectively. The 3-year disease-free survival after transplantation of the patients that received maintenance therapy was 80.0 ± 17.9%. The results of this pilot study indicated that pIFN α-2a containing induction and maintenance therapy was feasible and effective for ENKTCL.

Feasibility of the TNM-based staging system of ocular adnexal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).

The American Joint Committee on Cancer has proposed the tumor, node, metastasis (TNM) staging system to overcome the limitations of the Ann Arbor staging system for ocular adnexal lymphoma. We performed this study to evaluate the feasibility of the TNM staging system for ocular adnexal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (OAML). The data form 66 total eyes from 54 patients with biopsy-confirmed OAML according to World Health Organization classification were retrospectively analyzed. Using the TNM staging system, we reclassified all patients into two categories: (1) T1N0M0 stage group (n = 26), for patients with lymphoma involving only the conjunctiva; and (2) above T1N0M0 or bT1N0M0 stage group (n = 28), for patients with lymphoma extending to the orbit, eyelid, or adjacent structures, and/or bilateral OAML. After a 24-month median follow-up period for all patients, the T1N0M0 group revealed higher progression-free survival (PFS) than the above T1N0M0 or the bT1N0M0 group (P = 0.041). In a separate analysis of only 50 patients categorized as Ann Arbor stage IE, the T1N0M0 group demonstrated higher PFS (100%) than the above T1N0M0 or the bT1N0M0 group (84.7%; P = 0.067). Our data show that the poor prognostic group classified as Ann Arbor stage IE can be further distinguished by using the TNM staging system. Thus, further studies to develop treatment strategies for reducing relapse after treatment for OAML should use the TNM staging system.

The Conflict Between People's Urge to Punish AI and Legal Systems.

Regulating artificial intelligence (AI) has become necessary in light of its deployment in high-risk scenarios. This paper explores the proposal to extend legal personhood to AI and robots, which had not yet been examined through the lens of the general public. We present two studies (N = 3,559) to obtain people's views of electronic legal personhood vis-à-vis existing liability models. Our study reveals people's desire to punish automated agents even though these entities are not recognized any mental state. Furthermore, people did not believe automated agents' punishment would fulfill deterrence nor retribution and were unwilling to grant them legal punishment preconditions, namely physical independence and assets. Collectively, these findings suggest a conflict between the desire to punish automated agents and its perceived impracticability. We conclude by discussing how future design and legal decisions may influence how the public reacts to automated agents' wrongdoings.

Mantle cell lymphoma with gastrointestinal involvement and the role of endoscopic examinations.

BACKGROUND: Studies on gastrointestinal (GI) tract involvement in mantle cell lymphoma (MCL) are lacking. We investigated the clinical characteristics and prognosis of MCL with GI tract involvement. METHODS: We retrospectively analyzed 64 patients diagnosed with MCL from January 2009 to April 2017. At the time of MCL diagnosis, patients who were identified to have GI involvement by endoscopic or radiologic examination were assigned to the GI-MCL group. The other patients were assigned to the non GI-MCL group. RESULTS: The GI-MCL group included 28 patients (43.8%). The most common endoscopic finding of MCL was lymphomatous polyposis (20/28, 71.4%). The GI-MCL group had higher stage and International Prognostic Index status (P = 0.012 and P = 0.003, respectively). Among the total 51 GI lesions in the GI-MCL group, 31.4% (16/51) were detected only by endoscopic examinations and were not detected on CT or PET-CT. The cumulative incidence of recurrence was higher in the GI-MCL group compared with the non GI-MCL group but the difference was not statistically significant (P = 0.082). Stage (HR 1.994, 95% CI 1.007-3.948) and auto PBSCT (HR 0.133, 95% CI 0.041-0.437) were identified as independent predictive factors for recurrence. Recurrences at GI tract were identified in 59.1% (13/22) and 11.1% (2/18) of the GI-MCL and non GI-MCL group, respectively. Among 15 GI tract recurrences, five recurrences were detected only with endoscopic examinations. CONCLUSIONS: Endoscopy can reveal the GI involvement of MCL that is not visualized by radiological imaging. Endoscopic examinations are recommended during staging workup and the follow-up period of MCL patients.

Pattern of failure and optimal treatment strategy for primary gastric diffuse large B-cell lymphoma treated with R-CHOP chemotherapy.

PURPOSE: The optimal treatment for primary gastric diffuse large B-cell lymphoma (PG-DLBCL) is still unknown. We evaluated unfavorable prognostic factors and pattern of failure in PG-DLBCL to determine the optimal treatment strategy. METHODS: Between April 2001 and November 2018, 120 patients with complete remission following rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy were retrospectively reviewed. According to the Lugano staging system, 80 patients (66.7%) had localized disease and 40 patients (33.3%) had advanced disease. A total of 93 (77.5%) patients had single gastric lesion and 27 (22.5%) patients had multiple gastric lesions. Ninety patients (75%) were treated with R-CHOP chemotherapy alone and 30 patients (25%) received R-CHOP chemotherapy with additional local treatment for gastric lesions. RESULTS: The 5-year locoregional failure-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) rates in patients treated with R-CHOP chemotherapy with local treatment were 100%, 100%, and 100%, respectively, whereas the LRFS, PFS, and OS rates in patients treated with R-CHOP chemotherapy alone were 86.3%, 78.2%, and 87.4%, respectively (p = 0.031, p = 0.095, and p = 0.025, respectively). During the follow-up period, 17 patients (14.2%) had disease recurrence. Only 3 of the 17 patients had relapse in a completely new site without relapse in the initial involved site. All, except 2, cases of local recurrence included gastric failure. In the multivariate analysis, performance status and number of gastric lesions were independent prognostic factors for treatment outcome. CONCLUSIONS: Patients with complete remission following R-CHOP chemotherapy showed a good prognosis. The main pattern of failure in patients with PG-DLBCL was local recurrence, especially in the stomach. Patients who received local treatment for gastric lesions showed improved gastric control. Therefore, in patients with unfavorable prognostic factors, we recommend R-CHOP chemotherapy with additional local treatment for gastric lesions.

Analysis of the response time to involved-field radiotherapy in primary gastrointestinal low-grade B-cell lymphoma.

BACKGROUND: Early-stage primary gastrointestinal (GI) low-grade B-cell lymphoma shows good therapeutic response to primary radiotherapy. However, there is no clear guideline for the evaluation of response to radiation therapy currently. The aim of this study was to analyze the relationship between the best response time and the clinical course after radiotherapy. METHODS: Patients who underwent radiotherapy for treatment of primary GI low-grade B-cell lymphoma from September 2007 to December 2018 at Seoul St. Mary's Hospital were included. Early responders were defined by best response within 6 months after radiotherapy, and delayed responders after 6 months. Clinical and pathological factors associated with delayed response and survival analyses were performed to investigate the recurrence and survival during follow-up. RESULTS: A total of 43 patients were evaluated and the number of gastric mucosa-associated lymphoid tissue and duodenal follicular lymphoma was 36 and 7, respectively. All of 43 patients showed complete remission to radiotherapy and the best response time after radiotherapy was a median of 3 months. There were 8 delayed responders with a median duration of 8.9 months. Early and delayed responders were characterized by a significant difference in depth of invasion beyond the mucosal layer. CONCLUSIONS: Delayed responders did not show differences in oncological outcomes compared with early responders. They were allowed to watch and wait for an additional 6 to 12 months without further treatment.

Comparison of Selection and Long-term Clinical Outcomes Between Chemotherapy and Radiotherapy as Primary Therapeutic Modality for Ocular Adnexal MALT Lymphoma.

BACKGROUND: The choice of a primary treatment for ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) depends on the extent of tumor spread. However, radiotherapy is commonly used as a first-line therapy despite ophthalmic complications, because most OAMLs are in a limited stage of progression. However, the initial therapeutic modality, including chemotherapy and treatment of the advanced stage, has not been fully established for OAML. Therefore, we evaluated the optimal therapeutic options and survival outcome-related parameters for patients with primary OAML. METHODS: We evaluated 208 consecutive patients with primary OAML who were diagnosed at the Catholic University Lymphoma Group between January 2004 and April 2015. FINDINGS: During a median follow-up of 70.0 months (range, 3.2-182.0 months) in 208 patients with primary OAML, most patients were female and the median age was 46 years old. Overall survival (OS) and progression-free survival (PFS) at 13 years were excellent (92.7% and 69.7%, respectively). Of the 117 patients who received the first-line radiotherapy, 92% achieved complete remission (CR), usually by being treated with less than 30 Gy. Radiation-related ophthalmic complications including dry eye syndrome (59%) and cataract (22%) caused a decline in the quality of life (QoL). Chemotherapy alone was used to treat 86 OAML patients, with 84.9% achieving CR and 12.8% achieving partial remission with tolerable toxicities. There were no differences in survival outcomes between patients treated with radiotherapy versus those treated with rituximab-containing chemotherapy, although the latter group had more advanced stages of OAML (OS, p = 0.057; PFS, p = 0.075). INTERPRETATION: OAML patients were predominantly female and relatively young, and radiotherapy as a primary therapeutic option was more likely to lead to radiation-related complications, resulting in lower QoL. On the other hand, frontline chemotherapy showed consistent therapeutic outcomes with tolerable toxicities compared to radiotherapy, and there were no long-term or delayed adverse events. Therefore, when considering therapeutic efficacy and therapy-related QoL, chemotherapy is recommended for younger patients, and radiotherapy is recommended for older and chemotherapy-ineligible patients. FUNDING: A National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. NRF-2016R1A2B4007282).

A Study on the Procurement of HLA Class I Typing Trays Using Gushed Out Blood During Placental Delivery / 대한수혈학회지

BACKGROUND: Microlymphocytotoxicity test is most widely used for HLA Class I typing but almost all laboratories depend on imported HLA Class I typing trays. Matching criteria for the selection of HLA-matched platelets to treat platelet refractoriness is not as strict as for bone marrow transplantation. Therefore, with the acquisition of various antisera against high frequency HLA antigens, self-made HLA typing trays can be used for HLA typing of HLA-matched platelet donors. METHODS: 140 samples obtained during placental delivery were tested for the presence of HLA antibodies against a well-characterized panel of 90 cells. Specificity of HLA antisera were determined by evaluating the correlation coefficient r of the 2x2 table, kappa2 test. Antisera strength was evaluated by the strength index. RESULTS: HLA antibodies were detected in 25 samples by primary screening and 23 samples also showed a positive reaction in secondary screening (16%). Among 23 samples, 11 antisera were of reagent grade quality and 7 were monospecific antisera. DISCUSSION: Imported HLA typing trays can be replaced by harvesting HLA antisera against HLA antigens which are relatively common in Koreans through continuous HLA antibody screening using gushed out blood during placental delivery.