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Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the approach to patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). This study retrospectively analyzed patients treated with commercially available tisagenlecleucel at our hospital and evaluated its safety and effectiveness. Of the 21 patients evaluated, any grade and grade ≥3 cytokine release syndrome (CRS) occurred in 85.7% and 9.5% of the patients, respectively. A total of 66.7% received tocilizumab and 28.6% received glucocorticoids for the treatment of CRS. The complete response (CR) rate at 3 months was 61.9% (95% confidence interval [CI] 38.4-81.9). After a median follow-up of 6.3 months following CAR-T infusion, the progression-free survival (PFS) and overall survival rates at 6 months were 53.1% (95%CI 28.3-72.7) and 69.2% (95%CI 43.7-84.9), respectively. Severe cytopenia and hypogammaglobulinemia occurred frequently following CAR-T infusion. Eight patients (38.1%) had comorbidities that would have made them ineligible for leukapheresis in the JULIET trial. However, the presence of comorbidities at the time of leukapheresis had no significant effect on the rates of CR, PFS, and adverse events. Tisagenlecleucel for r/r DLBCL in the real-world setting showed high efficacy and manageable safety profile comparable with the pivotal trial.

Choriocarcinoma is a highly aggressive germ cell tumor and can metastasize to the brain. Although brain metastasis has a poor prognosis, the optimal treatment strategy remains unclear due to its low incidence. A 33-year-old man presenting with multiple lung nodules on chest radiography was referred to our hospital. Computed tomography revealed bilateral lung nodules and a large pelvic mass, and brain magnetic resonance imaging (MRI) demonstrated multiple brain lesions. He developed progressive headache and nausea and underwent two craniotomies because of rapid tumor growth and intratumoral hemorrhage. Metastasis of choriocarcinoma was strongly suspected because of histological findings and detection of urine human chorionic gonadotropin (hCG). He immediately received chemotherapy with bleomycin, etoposide, and cisplatin (BEP). Although the pelvic mass and pulmonary lesions reduced in size and the β-hCG level decreased after one cycle of BEP, brain MRI displayed an increase in the size and number of brain metastases. He underwent whole-brain radiotherapy (WBRT) concurrently with 2 cycles of BEP, leading to successful reduction of brain metastases. After 4 cycles of BEP, the β-hCG level was still higher than the normal range, and the pelvic and pulmonary lesions remained. He continued chemotherapy with paclitaxel, ifosfamide, and cisplatin (TIP) and etoposide, ifosfamide, and cisplatin (VIP). The β-hCG level normalized, and the residual pelvic mass was resected, revealing no viable cancer cells. Multimodal treatment, including two craniotomies and chemotherapy concurrent with WBRT, can achieve good control of lesions of the brain and other sites.

Standard regimens for extrapulmonary neuroendocrine carcinomas(EPNEC)are not established. Treatment used for small cell lung cancer is also used for EPNECs. Amrubicin(AMR) monotherapy is used as salvage therapy for small cell lung cancer, but its efficacy in EPNEC is not clear. The aim of this study was to estimate the efficacy of AMR monotherapy in EPNEC. We retrospectively investigated patients with EPNEC who received first-line platinum-based chemotherapy between April 2007 and March 2019. The time to treatment failure(TTF)and the efficacy and toxicity was analyzed in the patients who received AMR monotherapy. Among 43 patients with EPNEC, 14(13 males, one female; median age, 58 years)received AMR monotherapy. Primary site included the pancreas(n=3), stomach(n=3), rectum(n=1), anal canal(n=1), salivary glands(n= 1), urothelial(n=1), bladder(n=1), prostate(n=1), and 2 patients had primary unknown cancer. Pathological type included small cell(n=4), large cell(n=2), and other types(n=8). Prior chemotherapy comprised CDDP plus CPT-11(n =5), CDDP plus ETP(n=2), and CBDCA plus ETP(n=6). The median TTF was 49(20-61)days. One patient had a partial response and the disease control rate was 33%. The common adverse events ofGrade 3 were leukopenia(69%), neutropenia(62%), and febrile neutropenia(23%). AMR monotherapy was clinically effective and safe for EPNEC.

Maintaining relative dose intensity (RDI) of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improves the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). Pegfilgrastim was approved in Japan in November 2014 to prevent febrile neutropenia (FN) and maintain RDI.In this retrospective study, we reviewed 334 patients with DLBCL who received 6 or more courses of R-CHOP and analyzed the differences in the RDI, overall survival (OS), and progression-free survival between patients whose treatment started after November 2014 (postapproval group) and those whose treatment started before October 2014 (pre-approval group).The incidence of FN was lower (20% vs 38.3%, P .001) and the RDI of R-CHOP was higher (86.8% vs 67.8%, P .001) in the postapproval group. Pegfilgrastim was administered to many of these patients (76.8%) and was thought to have contributed to the high RDI maintenance in the postapproval group. Interrupted time-series analysis showed a significant rise of the RDI at the timing of pegfilgrastim approval in patients aged70 years (estimated change: 18.1%, P .001). The 5-year OS (85.7% vs 69.9%, P = .009) and progression-free survival (81.4% vs 64.4%, P = .011) were superior in the postapproval group. However, the differences were not significant in matched-pair analysis matching National Comprehensive Cancer Network-International Prognostic Index scores. Improved survival outcomes in this group were observed only among patients with Ann Arbor stage 3/4 (5-year OS: 83.7% vs 61.3%, P = .019) and high-risk on the National Comprehensive Cancer Network-International Prognostic Index (5-year OS: 80.7% vs 32.4%, P = .014). Multivariate analysis showed that a high RDI and low lactate dehydrogenase were associated with superior OS (RDI ≥ 85%, hazard ratio: 0.48, P = .016; lactate dehydrogenase institutional upper limit of normal, hazard ratio: 2.38, P = .005).The RDI of R-CHOP was able to be maintained at higher levels, the incidence of FN was lower, and significantly better clinical outcomes were achieved in clinically high-risk groups after pegfilgrastim approval. Maintaining a high RDI in R-CHOP by administering pegfilgrastim to those who are likely to have low RDI without it is important for achieving favorable outcomes in patients with DLBCL.

Chimeric antigen receptor (CAR) T-cell therapy is effective in treating relapsed and refractory B-cell non-Hodgkin lymphoma. However, because of the mortality risk associated with immune effector cell-associated neurotoxicity syndrome and pseudoprogression, patients with central nervous system (CNS) involvement are less likely to receive CAR T-cell therapy.We report a case of a 61-year-old, male patient with intravascular large B-cell lymphoma who suffered a CNS relapse after standard chemotherapy.A diagnosis of intravascular large B-cell lymphoma with CNS involvement was made.We treated the patient using CAR T-cell therapy following a conditioning regimen consisting of thiotepa and busulfan and autologous stem cell transplantation. Although he experienced grade 1 cytokine release syndrome, no other serious adverse events, such as immune effector cell-associated neurotoxicity syndrome or pseudoprogression, were observed.The patient achieved complete remission after the CAR T-cell infusion.CAR T-cell therapy following autologous stem cell transplantation is a viable option for relapsed/refractory lymphoma with CNS infiltration. Further clinical studies are warranted to verify its safety and efficacy.

Background: The COVID-19 pandemic has had various effects on clinical practice. Anticancer chemotherapy is no exception. This time, we investigated the trends of chemotherapy in our hospital and department under the COVID-19 pandemic, and report the results to examine the effects of the COVID-19 pandemic. Method: We count the number of outpatient chemotherapy and the number of hospitalizations in which chemotherapy was performed in our hospital and our department from January to August 2020. And the impact of the COVID-19 pandemic is investigated from changes in the number of patients and comparison with the same period of the previous year. Results: During the same period, outpatient chemotherapy was given to 1396 patients a total of 9647 times, and to 242 patients a total of 1237 times in our department. Compared to the same period of the previous year, it decreased by about 13% in the entire hospital and about 6% in our department. In addition, when compared monthly, there was no change from the previous year until January, and the downward trend began in February and reached the lowest number in May. After that, it showed a recovery trend, and although it recovered significantly in July, it did not recover to the previous year's level during the observation period. In addition, when the tendency within our department was investigated, a significant decrease was observed in the solid cancer group, but almost no change was observed in the lymphoma group. Conclusion: Outpatient chemotherapy was suppressed by the COVID-19 pandemic, but some treatment was given. In addition, although chemotherapy for the purpose of suppressing progression and alleviating symptoms decreased, it was speculated that chemotherapy for the purpose of curative treatment was performed as usual.

吸入ブデソニドは，持続性の局所抗炎症作用および気道選択性を有し，気管支喘息の治療薬としての高い効果が期待されてきた．細胞内のブデソニドは，エステル体では不活性だが，組織リパーゼによる緩徐な加水分解を受け活性化される．この可逆的エステル化により，組織内での曝露および受容体飽和が持続し，長時間の抗炎症作用が発揮される．この特性に関して，in vitro（ヒト気管上皮細胞）において脂肪酸エステル体生成が確認され，吸入投与後のヒト切除肺組織内においてもブデソニドと共にブデソニドエステル体が実際に存在することが確認された．さらに，副腎摘出ラットの気管内注入の研究では，ブデソニドは，エステル化を受けないプロピオン酸フルチカゾンと比較して，局所抗炎症作用がより長時間持続することが示された．一方，ブデソニド吸入投与後，血漿中および末梢組織内では，エステル化がほとんど認められないことがラットの研究で示された．ブデソニドの水性懸濁液によるブデソニド吸入を用いた米国での小児気管支喘息患者を対象とした臨床試験では，12週間投与における試験成績（4試験）より，有効性および安全性が確認され，52週間投与における試験成績（4試験）より，長期の安全性が示された．本邦では，6ヵ月から5歳未満の小児気管支喘息患者を対象に第III相オープン臨床試験（試験0765）が実施され，24週間投与での有効性および安全性が確認された．さらに，本試験の投与継続試験である試験0768では，最長96週間の長期投与においても安全性に懸念を示唆する所見ならびに徴候は認められなかった．以上より，ブデソニドは気管支喘息に対して高い効果と安全性が示された．本剤の導入によって，既存のステロイド薬の吸入を効率的に行えない乳幼児患者に対して，新たな治療薬を提供する機会を得たと考える．

Summary Monoflora chickens were established at the age of 2 days by an oral inoculation of one of six species of bacteria (Lactobacillus acidophilus, Bifidobacterium thermopbilum, Bacteroides vulgatus, Clostridium perfringens, Escherichia coli, or Streptococcus faecalis). Two days later the chickens were infected with Eimeria tenella (5 × 104 oocysts per bird). There were four groups: uninfected birds as controls, the birds infected with either bacteria or E. tenella alone, and the birds infected with bacteria and E. tenella. As observed under the scanning electron microscope (SEM) seven days after E. tenella infection, damage of the cecal mucosa in all groups infected with bacteria + E. tenella was more severe than in that infected with E. tenella alone. Most severe damage to the cecal mucosa was found in the birds infected with either C. perfringens or B. thermophilum combined with E. tenella.

The δ- and β-oxoester 1 and 5 underwent the Type II photoreaction to give the stereoisomeric cyclobutanol 2 and 6, respectively; the ethoxycarbonyl group in the esters determines the stereochemistry of 1,4-biradical cyclization.