記述言語：英語   掲載種別：研究論文（学術雑誌）  

We describe the case of a 36-year-old man diagnosed with human immunodeficiency virus (HIV) following prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. The patient had a complication of pneumocystis pneumonia. Upon initiating highly active antiretroviral therapy, we monitored HIV RNA levels, CD4+ T-cell count, SARS-CoV-2 viral load, and IgG antibodies against SARS-CoV-2. At 167 days post SARS-CoV-2 diagnosis, the patient's CD4+ T-cell count increased to 180 cells/μL. IgG antibodies against SARS-CoV-2 were undetectable despite a decreased SARS-CoV-2 viral load. HIV screening is necessary in cases of prolonged SARS-CoV-2 pneumonia or persistent SARS-CoV-2 shedding. When diagnosed with HIV infection, it is advisable to consider the possibility of pneumocystis pneumonia.

DOI： 10.7759/cureus.51189

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Multiple myeloma (MM), a neoplasm of plasma cells (PCs), is a highly heterogeneous disease with multifocal dissemination throughout the body. Minimal residual disease (MRD) detected using PCs in bone marrow (BM) is important for MM management; however, frequent invasive examinations impose a significant burden on patients. METHODS: Analysis using plasma cell-free DNA (cfDNA) might represent an alternative tool for disease monitoring. In this study, we observed the disease status in a patient with MM by examining the KRAS mutation allele frequency (MAF) in plasma cfDNA using digital PCR. RESULTS: During treatment, the MAF was correlated with serum immunoglobulin A and free light chain-kappa levels. After the second autologous peripheral blood stem cell transplantation, the KRAS MAF became immediately positive after confirming MRD negativity using PCs from BM. Shortly thereafter, the patient experienced clinical relapse primarily involving bone lesions. CONCLUSION: Mutant KRAS monitoring in cfDNA using serial blood collection might reflect the disease status more accurately than invasive BM examinations, especially in patients with MM whose primary lesions have extra-BM locations. It could also help predict treatment responses and outcomes.

DOI： 10.1016/j.cca.2023.117590

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 53-year-old man was presented with fever, eyelid edema, and thrombocytopenia. Based on examination outcomes, he was diagnosed with immune thrombocytopenia. He was prescribed prednisolone (PSL) at 0.5 mg/kg/day; subsequently, his platelet count improved and fever improved. PSL dose was tapered and stopped without relapse. However, 1 month later, the patient presented to our hospital with fever, generalized edema, thrombocytopenia, and acute renal failure. Computed tomography revealed multiple lymphadenopathies, hepatomegaly, pleural effusion, and ascites. Bone marrow biopsy indicated reticulin fibrosis, and lymph node biopsy revealed mixed-type Castleman disease. Based on these findings, he was diagnosed with grade 5 TAFRO syndrome (very severe). Steroid pulse therapy and tocilizumab were ineffective in improving his condition. Therefore, rituximab was administered instead of tocilizumab, and his condition eventually improved. The optimal treatment for TAFRO syndrome is yet to be established. If tocilizumab is ineffective as the second-line treatment, then rituximab might be effective.

DOI： 10.11406/rinketsu.64.265

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Posttransplant lymphoproliferative disease (PTLD) is a critical complication of hematopoietic stem cell transplantation (HSCT). PTLD is classified into early and late-onset PTLDs. In post-HSCT patients, late-onset PTLD is rare, particularly PTLD after HSCT for Epstein-Barr virus (EBV)-related lymphoproliferative disease. Here, we report the case of a patient diagnosed with late-onset EBV-related hemophagocytic lymphohistiocytosis (HLH), that of PTLD, after HSCT for chronic active EBV infection (CAEBV), that of EBV related lymphoproliferative disease, probably because of EBV reactivation. PATIENT CONCERNS AND DIAGNOSIS: A 22-year-old woman with abdominal fullness visited our hospital. Blood examination showed pancytopenia with atypical lymphocytes, liver dysfunction, and elevated lactate dehydrogenase level. In contrast, bone marrow aspiration showed slight hemophagocytosis with increased natural-killer cells (NK cells). As serum antibodies against EBV were atypical, we calculated the EBV-DNA level in peripheral blood and this level was significantly high. EBV was infected with NK cells, and EBV's monoclonality in NK cells was confirmed. Thus, the patient was diagnosed with CAEBV. INTERVENTIONS AND OUTCOMES: The patient received chemotherapy and cord blood cell transplantation (CBT); CAEBV was well controlled. Approximately 6years from CBT for CAEBV, she visited our hospital because of fever. Blood examination revealed pancytopenia with atypical lymphocytes, liver dysfunction, and elevated lactate dehydrogenase level. In contrast, bone marrow aspiration showed hemophagocytosis with increased B and T cell counts without increased NK cell count. Additionally, serum antibody titers against EBV were atypical, and the EBV-DNA level in the peripheral blood was high. EBV was infected with only B cells, and EBV's monoclonality was confirmed. A more detailed analysis indicated that EBV-specific cytotoxic T lymphocytes were inactive. Therefore, she was diagnosed with late-onset EBV-related HLH. She received extensive treatment, but EBV-related HLH did not improve. Finally, she died about 3 weeks after diagnosis. CONCLUSION: PTLD, including HLH, is a life-threatening complication after transplantation, including HSCT. To our knowledge, this is the first case of late-onset EBV-related HLH after CBT for CAEBV. Late-onset PTLD has an indolent clinical course, but our patient's disease course was extremely aggressive. Therefore, late-onset EBV-related PTLD may be life-threatening.

DOI： 10.1097/MD.0000000000029055

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Recent studies have revealed that tumor cells decrease their immunogenicity by epigenetically repressing the expression of highly immunogenic antigens to survive in immunocompetent hosts. We hypothesized that these epigenetically hidden "stealth" antigens should be favorable targets for cancer immunotherapy due to their high immunogenicity. To identify these stealth antigens, we treated human lung cell line A549 with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5Aza) and its prodrug guadecitabine for 3 d in vitro and screened it using cDNA microarray analysis. We found that the gene encoding sperm equatorial segment protein 1 (SPESP1) was re-expressed in cell lines including solid tumors and leukemias treated with 5Aza, although SPESP1 was not detected in untreated tumor cell lines. Using normal human tissue cDNA panels, we demonstrated that SPESP1 was not detected in normal human tissue except for testis and placenta. Moreover, we found using immunohistochemistry SPESP1 re-expression in xenografts in BALB/c-nu/nu mice that received 5Aza treatment. To assess the antigenicity of SPESP1, we stimulated human CD4+ T-cells with a SPESP1-derived peptide designed using a computer algorithm. After repetitive stimulation, SPESP1-specific helper T-cells were obtained; these cells produced interferon-γ against HLA-matched tumor cell lines treated with 5Aza. We also detected SPESP1 expression in freshly collected tumor cells derived from patients with acute myeloid leukemia or lung cancer. In conclusion, SPESP1 can be classified as a stealth antigen, a molecule encoded by a gene that is epigenetically silenced in tumor cells but serves as a highly immunogenic antigen suitable for cancer immunotherapy.

DOI： 10.1111/cas.14973

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against factor VIII (FVIII). Hematological malignancies, especially lymphoid malignancies, are known to be underlying causes of AHA; however, thus far, there is no report of AHA associated with Epstein-Barr-virus-associated T/natural killer-cell lymphoproliferative disease (EBV-T/NK-LPD). Here, we present a case of AHA that developed during treatment for EBV-T/NK-LPD. HISTORY: A 69-year-old man visited our hospital because of general fatigue. Blood examination showed pancytopenia, and computed tomography revealed whole-body lymphadenopathy, but there were no findings indicating hematological malignancy from bone marrow aspiration and cervical lymph node biopsy. The level of EBV DNA in peripheral blood was extremely high, and he was diagnosed with EBV-T/NK-LPD. EBV-T/NK-LPD improved with prednisolone (PSL) administration. Seventeen months after starting treatment, the patient complained of back and right leg pain. At that time, he had been treated with low-dose PSL, and EBV-T/NK-LPD was well controlled. Imaging revealed hematoma of the right iliopsoas muscle. Prolonged activated partial thromboplastin time (APTT) was the only abnormal finding in a screening coagulation test. FVIII coagulant activity was below detection limit, and FVIII inhibitor level was increased. From these results, he was diagnosed with AHA.A higher dose of PSL was administered, and, after 1 month of treatment, FVIII activity gradually increased, and FVIII inhibitor level became undetectable. APTT also normalized, and complete remission was achieved and maintained for 13 months with low-dose PSL. During treatment, EBV-T/NK-LPD was well controlled. CONCLUSION: It is speculated that proliferating lymphocytes interfere with normal immune functions and that abnormal autoantibodies are produced from those lymphocytes in patients with LPD. Therefore, we speculate that EBV-infected and proliferating monoclonal NK cells might have modulated the immune system and produced autoantibodies against FVIII, thus causing AHA in this patient with EBV-T/NK-LPD.

DOI： 10.1097/MD.0000000000025518

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 67-year-old man with relapsed anaplastic large cell lymphoma received salvage chemotherapy, and pegfilgrastim was used to prevent febrile neutropenia. On day 18 of chemotherapy, he developed a pseudogout attack. Although the first symptoms improved, another pseudogout attack occurred when he received the second course of chemotherapy and pegfilgrastim. Filgrastim was then used for the third course of chemotherapy, and a pseudogout attack did not occur. The serum granulocyte-stimulating factor (G-CSF) level was extremely elevated only when pegfilgrastim was used, suggesting a relationship between pseudogout and G-CSF. Pseudogout should be recognized as an adverse effect of pegfilgrastim.

DOI： 10.2169/internalmedicine.9362-17

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12185-017-2212-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12185-016-2141-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12185-016-2054-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bbrc.2016.05.153

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.cca.2014.07.013

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