{"title":"[Development of Lomentospora prolificans infection during induction therapy with venetoclax and azacitidine for acute myeloid leukemia].","authors":"Wakana Takahashi, Tatsuya Hatada, Chizuru Saito, Ryoichi Murata, Mikio Ueda, Toshihiro Miyamoto","doi":"10.11406/rinketsu.65.742","DOIUrl":"https://doi.org/10.11406/rinketsu.65.742","url":null,"abstract":"<p><p>Lomentospora prolificans is a rare filamentous fungus that causes invasive fungal disease (IFD) in immunocompromised patients with hematological malignancies, as well as hematopoietic cell or solid organ transplant recipients. A 75-year-old woman was diagnosed with acute myeloid leukemia, and started induction therapy with azacitidine and adjusted-dose venetoclax along with antifungal prophylaxis with fluconazole. On day 7, she became febrile and chest CT imaging showed multiple nodules in both lung fields, and the serum galactomannan antigen index became positive, indicating probable IFD. Anti-fungal therapy with liposomal amphotericin B was immediately initiated; however, the patient's condition rapidly deteriorated, and she died on day 15. L. prolificans was later identified in blood culture tests that had been repeatedly performed while she had been febrile. L. prolificans is generally resistant to most antifungal agents, which can make it fatal. As early definitive diagnosis is difficult, it may be appropriate to consider combination therapy when conventional anti-IFD therapy seems inadequate.</p>","PeriodicalId":93844,"journal":{"name":"[Rinsho ketsueki] The Japanese journal of clinical hematology","volume":"65 8","pages":"742-746"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Development of novel bispecific antibody therapy for multiple myeloma].","authors":"Tatsuya Konishi, Toshiki Ochi, Katsuto Takenaka","doi":"10.11406/rinketsu.65.428","DOIUrl":"10.11406/rinketsu.65.428","url":null,"abstract":"<p><p>Over the past decade, new therapeutic modalities have markedly improved clinical outcomes for patients with multiple myeloma. Recently, immunotherapy using both bispecific antibodies (BsAb) and chimeric antigen receptor T cells (CAR-T cells) has induced further anti-myeloma responses. Different agents must be combined to overcome the heterogeneity of myeloma cell clones, and new modalities for the treatment of refractory myeloma must also be developed to strengthen therapeutic effects. We have developed a novel BiTE (bispecific T-cell engager)-based modality, referred to as bridging-BiTE (B-BiTE). B-BiTE is able to bind to both an Fc domain of a human immunoglobulin G monoclonal antibody (mAb) and the human CD3 molecule. This enables rapid generation of a mAb/B-BiTE complex and safely induces dual-lymphoid activation of both human T cells and NK cells against myeloma cells. Importantly, sequential immunotherapy using two different mAb/B-BiTE complexes can produce deep and durable anti-myeloma responses. To further advance treatment of multiple myeloma, it is important to determine how to combine and sequence immunotherapy with other agents while considering management of unique adverse events caused by activated immune cells.</p>","PeriodicalId":93844,"journal":{"name":"[Rinsho ketsueki] The Japanese journal of clinical hematology","volume":"65 5","pages":"428-438"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Recent advances in prevention and treatment of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation].","authors":"Tomomi Toubai, Yuka Hosokawa","doi":"10.11406/rinketsu.65.401","DOIUrl":"10.11406/rinketsu.65.401","url":null,"abstract":"<p><p>Chronic graft-versus-host disease (cGVHD) negatively impacts long-term survival and quality of life (QOL) after allogeneic hematopoietic cell transplantation. Corticosteroids are the first-line treatment for cGVHD, but approximately 30% to 70% of patients develop steroid-refractory cGVHD (SR-cGVHD), which has an extremely poor prognosis. The pathophysiology of cGVHD is more complicated than acute GVHD, but recent advances using murine models in conjunction with human studies indicate three major phases: 1) acute inflammation, 2) chronic inflammation with loss of immune tolerance, and 3) disrupted target organ homeostasis and fibrosis. Strategies that help prevent cGVHD include optimal donor selection and choice of conditioning regimen as well as pharmacologic and graft manipulation strategies. The key cellular mediators of SR-cGVHD are T cells, B cells, antigen-presenting cells, and fibroblasts. T cells and B cells are now targetable with the inhibitors ibrutinib and ruxolitinib, respectively. Recently, promising results have been obtained by modulating pathologic T cell responses with Rock2 inhibitors and targeting fibrosis with CSF-1R inhibitors. To optimize the use of these medications, a better understanding of the biological and target organ-specific mechanisms of cGVHD is needed. Here we review recent advances in cGVHD pathogenesis and discuss how best to implement recently approved biology-driven treatments for cGVHD.</p>","PeriodicalId":93844,"journal":{"name":"[Rinsho ketsueki] The Japanese journal of clinical hematology","volume":"65 5","pages":"401-411"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Improvement of tissue fibrosis in TAFRO syndrome by prednisolone monotherapy].","authors":"Takao Kashiwagi, Yuki Kashiwagi, Tomohide Suzuki, Manami Shingu, Sayaka Kashiwagi, Tamaki Hirata, Junko Hori, Keikichi Miyata, Miho Takechi, Minoru Kishi, Takamasa Ohnishi, Yoshio Katayama, Masahide Iwai, Toshimitsu Matsui","doi":"10.11406/rinketsu.65.237","DOIUrl":"https://doi.org/10.11406/rinketsu.65.237","url":null,"abstract":"<p><p>We report the case of a 48-year-old man who presented with fatigue and weight loss. A local physician observed elevated alkaline phosphatase levels, anemia, thrombocytopenia, and renal dysfunction. Fever also appeared, and the patient was admitted to our hospital. Computed tomography revealed hepatosplenomegaly, pleural and ascitic fluid, and left axillary lymphadenopathy. Bone marrow biopsy indicated hyperplasia with increased megakaryocytes and reticulin fibrosis. Axillary lymph node biopsy showed Castleman's disease-like features. Liver biopsy revealed proliferation of reticulin fibrosis. Therefore, TAFRO syndrome was diagnosed and treatment with 1 mg/kg prednisolone was started. Anemia and thrombocytopenia improved, and after 24 weeks of treatment, serum hyaluronic acid and type IV collagen decreased to the normal range. Bone marrow biopsy after 18 weeks of treatment showed decreased reticular fibers. In TAFRO syndrome, improvement of liver and bone marrow fibrosis can be expected with adequate intervention, and serum hyaluronic acid and type IV collagen are useful for evaluating fibrosis.</p>","PeriodicalId":93844,"journal":{"name":"[Rinsho ketsueki] The Japanese journal of clinical hematology","volume":"65 4","pages":"237-242"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Multiple myeloma with IgH::MYC and multiple extramedullary lesions].","authors":"Yuto Sasaki, Satoshi Ichikawa, Kazuki Sakurai, Hiroshi Nakamura, Kyoko Inokura, Koichi Onodera, Noriko Fukuhara, Yasushi Onishi, Hisayuki Yokoyama, Hideo Harigae","doi":"10.11406/rinketsu.65.147","DOIUrl":"https://doi.org/10.11406/rinketsu.65.147","url":null,"abstract":"<p><p>A 41-year-old woman with right shoulder pain was found to have multiple tumors with osteolysis and M-proteinemia. Abnormal plasma cells (CD38+, CD138+, Igλ≫κ) were detected in 1.4% of bone marrow nucleated cells, and G-banding analysis revealed a 46,XX,t (8;14), (q24;q32) karyotype in 4 of 20 cells analyzed. A biopsy specimen from an extramedullary lesion had a packed proliferation of aberrant plasmacytoid cells with positive IgH::MYC fusion signals on fluorescence in situ hybridization. The patient was diagnosed with symptomatic multiple myeloma and treated with the BLd regimen, which significantly reduced M protein levels. Extramedullary lesions were initially reduced, but increased again after four cycles. The lesions disappeared with subsequent EPOCH chemotherapy and radiation, and complete remission was confirmed. The patient was then treated with high-dose chemotherapy with autologous peripheral blood stem cell transplantation. Complete remission was maintained for over one year with lenalidomide maintenance therapy. A solitary IgH::MYC chromosomal translocation is extremely rare in multiple myeloma and may be associated with high tumor proliferative capacity, multiple extramedullary lesions, and poor prognosis. Combined therapeutic modalities with novel and conventional chemotherapy and radiation might be a promising treatment strategy for patients with this type of multiple myeloma.</p>","PeriodicalId":93844,"journal":{"name":"[Rinsho ketsueki] The Japanese journal of clinical hematology","volume":"65 3","pages":"147-152"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"","authors":"","doi":"10.11406/rinketsu.65.124","DOIUrl":"10.11406/rinketsu.65.124","url":null,"abstract":"","PeriodicalId":93844,"journal":{"name":"[Rinsho ketsueki] The Japanese journal of clinical hematology","volume":"65 2","pages":"124"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140051266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Discontinuation of tyrosine kinase inhibitors before epiphyseal closure leading to improved short stature in pediatric chronic myelogenous leukemia].","authors":"Wataru Fukui, Taemi Ogura, Shohei Azumi, Hideto Ogata, Koji Kawaguchi, Takayuki Takachi, Yasuo Horikoshi, Ayumi Uematsu, Hiroyuki Shimada, Kenichiro Watanabe","doi":"10.11406/rinketsu.65.175","DOIUrl":"https://doi.org/10.11406/rinketsu.65.175","url":null,"abstract":"<p><p>A 3-year-old boy was referred to our hospital with splenomegaly. Blood tests revealed hyperleukocytosis and bone marrow examination showed major BCR::ABL1 fusion, leading to the diagnosis of chronic myelogenous leukemia (CML). Due to intolerance, the tyrosine kinase inhibitor (TKI) was changed from imatinib to dasatinib to nilotinib. The patient achieved molecular remission but became markedly short in stature, measuring 129.3 cm (height standard deviation score [SDS] -3.3) at the age of 12. TKI therapy was discontinued at age 12 years and 10 months, which was 9 years and 8 months after the start of TKI and 1 year and 6 months after achievement of MR4.0, as discontinuation before epiphyseal closure would not improve short stature. At 2 years and 6 months after discontinuation, the patient's height improved to 156.1 cm (SDS-2.0) without relapse. Growth suppression by TKIs is a problem in the management of pediatric CML. This case illustrates how improvement in severe short stature can be achieved by discontinuing TKI therapy before epiphyseal closure.</p>","PeriodicalId":93844,"journal":{"name":"[Rinsho ketsueki] The Japanese journal of clinical hematology","volume":"65 3","pages":"175-179"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Overview].","authors":"Momoko Nishiko","doi":"10.11406/rinketsu.65.529","DOIUrl":"https://doi.org/10.11406/rinketsu.65.529","url":null,"abstract":"","PeriodicalId":93844,"journal":{"name":"[Rinsho ketsueki] The Japanese journal of clinical hematology","volume":"65 6","pages":"529"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Overview].","authors":"Takahiro Suzuki","doi":"10.11406/rinketsu.65.502","DOIUrl":"https://doi.org/10.11406/rinketsu.65.502","url":null,"abstract":"","PeriodicalId":93844,"journal":{"name":"[Rinsho ketsueki] The Japanese journal of clinical hematology","volume":"65 6","pages":"502"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Epigenetic dysregulation and emerging treatment strategies in myelodysplastic syndromes].","authors":"Hiroyoshi Kunimoto","doi":"10.11406/rinketsu.65.362","DOIUrl":"10.11406/rinketsu.65.362","url":null,"abstract":"<p><p>The epigenome regulates transcription of target genes through DNA methylation- or histone methylation/acetylation/phosphorylation/ubiquitination-mediated alteration of genomic function or chromatin conformation. Recent genomic studies have shown that multiple genes encoding epigenetic regulators are frequently and recurrently mutated in MDS, suggesting that epigenetic dysregulation is significantly associated with the molecular pathogenesis and clinical features of MDS. In this review, we will present our recent findings together with others, focusing on physiological molecular functions of epigenetic regulators recurrently mutated in MDS and on functional correlation between dysregulated epigenomic regulators and molecular pathogenesis/clinical features of MDS.</p>","PeriodicalId":93844,"journal":{"name":"[Rinsho ketsueki] The Japanese journal of clinical hematology","volume":"65 5","pages":"362-374"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}