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The classification of clonal plasmacytoid dendritic cell (pDC) proliferation associated with myeloid neoplasms remains a topic of ongoing debate. Although the fifth edition of the World Health Organization classification classifies clonal pDC proliferation into two categories, it is unclear whether this classification adequately captures the complexities of clonal pDC pathogenesis. We present a clinical case featuring myeloid sarcoma with pDC-like cells in cervical lymph nodes and bone marrow (BM). Analysis of biopsy specimens and BM aspirate revealed two distinct cellular populations expressing myeloid and pDC markers. One population exhibited myeloid leukemia and monocyte markers, including MPO, CD13, CD33, CD11b, and CD14, while the other manifested an immunophenotype reminiscent of pDCs, characterized by expression of CD56 and CD123. Additionally, whole exome sequencing and RNA sequencing of BM mononuclear cells were conducted to explore the pathophysiology of this rare malignancy, and unveiled pDC-like cell proliferation driven by IKZF1 and ETV6 mutations originating from clonal hematopoiesis initiated by a DNMT3A mutation. Notably, venetoclax-based therapy exhibited efficacy for achieving and sustaining complete remission. This case provides pivotal insights into the mechanistic aspects of pDC/pDC-like cell proliferation in myeloid sarcoma, offering valuable perspectives on therapeutic strategies.
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BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact, with millions of confirmed cases and deaths worldwide. While most cases are mild, a subset progresses to severe respiratory complications and death, with factors such as thromboembolism, age, and underlying health conditions increasing the risk. Vascular endothelial damage has been implicated in severe outcomes, but specific biomarkers remain elusive. This study investigated syndecan-1 (SDC-1), a marker of endothelial damage, as a potential prognostic factor for COVID-19, focusing on the Japanese population, which is known for its aging demographics and high prevalence of comorbidities. METHODS: A multicenter retrospective study of COVID-19 patients in Fukushima Prefecture in Japan who were admitted between February 2020 and August 2021 was conducted. SDC-1 levels were measured along with other clinical and laboratory parameters. Outcomes including thrombosis, 28-day survival, and disease severity were assessed, and disease severity was categorized according to established guidelines. RESULTS: SDC-1 levels were correlated with disease severity. Patients who died from COVID-19 had greater SDC-1 levels than survivors, and the area under the receiver operating characteristic curve (AUC) analysis suggested the potential of the SDC-1 level as a predictor of mortality (AUC 0.714). KâM analysis also revealed a significant difference in survival based on an SDC-1 cutoff of 10.65 ng/mL. DISCUSSION: This study suggested that SDC-1 may serve as a valuable biomarker for assessing COVID-19 severity and predicting mortality within 28 days of hospitalization, particularly in the Japanese population. However, further investigations are required to assess longitudinal changes in SDC-1 levels, validate its predictive value for long-term survival, and consider its applicability to new viral variants. CONCLUSIONS: SDC-1 is emerging as a potential biomarker for assessing the severity and life expectancy of COVID-19 in the Japanese population, offering promise for improved risk stratification and patient management in the ongoing fight against the virus.
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Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by the BCR::ABL1 tyrosine kinase. Tyrosine kinase inhibitors (TKIs) have been established as standard therapies for CML. However, some CML patients experience TKI intolerance. Asciminib was approved for CML patients either intolerant or refractory to TKI therapy. We herein report a 63-year-old CML patient who underwent renal transplantation and exhibited TKI intolerance. He was switched to asciminib, which achieved a deep molecular response without exacerbation of the renal function. Our experience revealed that asciminib is effective and safe for CML patients complicated with chronic kidney disease.
Assuntos
Transplante de Rim , Leucemia Mielogênica Crônica BCR-ABL Positiva , Niacinamida/análogos & derivados , Pirazóis , Insuficiência Renal Crônica , Masculino , Humanos , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas de Fusão bcr-abl , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive subtype of myeloid malignancy characterized by skin, lymph node and central nervous system (CNS) involvement. Although various regimens are used, a standard therapeutic strategy for BPDCN has not been established. Recent studies revealed that BPDCN patients frequently have a mutation in ZRSR2, which is a minor spliceosome component. However, the association between the clinical features of BPDCN and ZRSR2 mutational status remains unknown. A 70-year-old man was referred to our hospital with skin rash and enlarged lymph nodes, as well as blasts in the peripheral blood. BPDCN was diagnosed based on the immunophenotype of the blasts derived from bone marrow. Whole exome sequencing revealed that BPDCN cells collected at diagnosis had mutations in ZRSR2, ZBTB33, CUL3, TET2 and NRAS. RNA sequencing analysis indicated that U12-type intron retention occurred in LZTR1, caused by ZRSR2 loss. After seven cycles of venetoclax combined with azacitidine therapy, BPDCN cells appeared in the peripheral blood and infiltrated the CNS. Two KRAS mutated clones appeared at BPDCN recurrence. These findings are important for understanding the pathogenesis of BPDCN, which will inform development of novel therapeutic strategies.
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Neoplasias Hematológicas , Neoplasias Cutâneas , Masculino , Humanos , Idoso , Células Dendríticas/patologia , Neoplasias Cutâneas/patologia , Transdução de Sinais , Evolução Clonal/genética , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patologia , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Proteínas Culina/genética , Proteínas Culina/metabolismo , Fatores de Transcrição/genéticaRESUMO
Myelodysplastic neoplasms (MDS) are defined by cytopenia and morphologic dysplasia originating from clonal hematopoiesis. They are also frequently complicated with diseases caused by immune dysfunction, such as Behçet's disease (BD) and secondary pulmonary alveolar proteinosis (sPAP). MDS with both BD and sPAP is extremely rare, and their prognosis is poor. In addition, haploinsufficiency of the hematopoietic transcription factor gene GATA2 is recognized as a cause of familial MDS and is frequently complicated by sPAP. Herein, we report a case of MDS combined with both BD and sPAP in association with GATA2 deficiency in a Japanese woman. Because she developed progressive leukopenia and macrocytic anemia during BD treatment at the age of 61, she underwent a bone-marrow examination and was diagnosed with MDS. She subsequently developed sPAP. At the age of 63, she underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Since allo-HSCT, she has maintained complete remission of MDS as well as the symptoms of BD and sPAP. Furthermore, we performed whole exome sequencing and identified the GATA2 Ala164Thr germline mutation. These findings suggest that patients with MDS, BD and sPAP should be considered for early allo-HSCT.
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Síndrome de Behçet , Transplante de Células-Tronco Hematopoéticas , Leucopenia , Síndromes Mielodisplásicas , Neoplasias , Proteinose Alveolar Pulmonar , Feminino , Humanos , Proteinose Alveolar Pulmonar/genética , Proteinose Alveolar Pulmonar/terapia , Síndrome de Behçet/complicações , Síndrome de Behçet/terapia , Neoplasias/complicações , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Mutação em Linhagem Germinativa , Fator de Transcrição GATA2/genéticaRESUMO
The patient was a 40-year-old woman referred to our hospital after an anterior mediastinal tumor was detected. Imaging findings revealed a tumor with irregular margins and a marked tendency to infiltrate, with some calcification. Rather than malignant lymphoma, thymic carcinoma or high-grade invasive thymoma was suspected. Endobronchial ultrasound-guided transbronchial needle aspiration biopsy and computed tomography-guided needle biopsy were performed, but no diagnosis was made. Mediastinal tumor biopsy by video-assisted thoracic surgery led to the diagnosis of primary mediastinal large B-cell lymphoma, spindle cell variant. A retrospective examination of the needle biopsy specimens revealed that some tissues considered to have been crushed were composed of spindle-shaped lymphoma cells. This study indicates that it is crucial to note that there is a subtype of primary mediastinal large B-cell lymphoma with an unusual pathological morphology.
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Linfoma de Células B , Neoplasias do Mediastino , Feminino , Humanos , Adulto , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/patologia , Estudos Retrospectivos , Mediastino/diagnóstico por imagem , Mediastino/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Linfoma de Células B/patologiaRESUMO
Peripheral blood stem cell harvest (PBSCH) is a crucial procedure for autologous stem cell transplantation in patients with multiple myeloma. We herein report a retrospective study to verify the usefulness of bortezomib and high-dose cyclophosphamide therapy (Bor-HDCY) as a conditioning regimen for PBSCH. Thirty-three patients were evaluated. The median age at the first apheresis was 61 (interquartile range, 53-64) years old, and 18 (54.5%) patients were male. Bor-HDCY was performed in 15 patients, and HDCY was performed in 18. In the patients who underwent Bor-HDCY, the CD34+ cell count at the first apheresis was significantly higher than in the others (P<0.01), and the total CD34+ cell count also tended to be high (P=0.0933). In terms of apheresis days, two-thirds of the patients who underwent HDCY had two-day apheresis, whereas most who underwent Bor-HDCY had one-day apheresis. According to univariate analysis, Bor-HDCY (P<0.01), VRd (Bor, lenalidomide, and dexamethasone) as induction therapy (P=0.0529), and ≥VGPR before PBSCH (P=0.0767) were factors associated with a higher CD34+ cell count at first apheresis. Although multivariate analysis showed that there were no independently significant factors influencing the CD34+ cell count at the first apheresis, the stepwise selection method revealed that only the Bor-HDCY regimen remained in the final model (P<0.005). Bor-HDCY may be a useful conditioning regimen for increasing the CD34+ cell yield.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Células-Tronco de Sangue Periférico , Antígenos CD34 , Bortezomib , Ciclofosfamida , Dexametasona , Feminino , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas , Humanos , Lenalidomida , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Transplante AutólogoRESUMO
Acquired hemophilia A (AHA) is a bleeding disorder caused by the acquired appearance of inhibitor for factor VIII. Approximately half of all patients with AHA have some type of underlying disease. We herein report the case of a 72-year-old Japanese man with AHA who presented with infectious aortic aneurysms due to an underlying Helicobacter cinaedi infection. To our knowledge, this is the first report of AHA triggered by a bacterial infection; however, there may be similar cases that remain undiagnosed because this pathogen is difficult to identify. Clinicians should consider the possibility of H. cinaedi as a causative pathogen in patients presenting with a fever of unknown origin.
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Aneurisma Aórtico , Bacteriemia , Infecções por Helicobacter , Helicobacter , Hemofilia A , Idoso , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Hemofilia A/complicações , Hemofilia A/diagnóstico , Humanos , MasculinoRESUMO
Lymphoproliferative diseases have been associated with various autoimmune diseases. We experienced a case of non-chronic lymphocytic leukemia type monoclonal B-cell lymphocytosis (MBL) that was exacerbated by increasing prednisolone for dermatomyositis and then improved by decreasing the dosage. Because MBL is difficult to diagnose, cases like ours may not be rare. These findings will facilitate our understanding of the mechanism underlying lymphoproliferative diseases and autoimmune diseases.
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Dermatomiosite , Leucemia Linfocítica Crônica de Células B , Linfocitose , Linfócitos B , Dermatomiosite/induzido quimicamente , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfocitose/induzido quimicamente , Linfocitose/diagnóstico , Prednisolona/efeitos adversosRESUMO
We herein report the case of a 54-year-old Japanese man with hepatitis C virus (HCV)-related membranoproliferative glomerulonephritis (MPGN), which developed at the time of relapse of immune thrombocytopenic purpura (ITP) after rituximab therapy. Antiviral therapy for HCV led to the improvement of both MPGN and ITP. Rituximab therapy may have contributed to the exacerbation of HCV infection and induced the development of HCV-related MPGN and the relapse of ITP. Our case suggested that HCV treatment should be prioritized over rituximab therapy for HCV-positive patients with ITP and that antiviral therapy for HCV may be effective for treating ITP itself.
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Glomerulonefrite Membranoproliferativa , Hepatite C , Púrpura Trombocitopênica Idiopática , Glomerulonefrite Membranoproliferativa/complicações , Glomerulonefrite Membranoproliferativa/tratamento farmacológico , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Rituximab/efeitos adversosRESUMO
Donor cell-derived leukemia and myelodysplastic syndrome (DCL) is a rare complication in patients after allogenic stem cell transplantation (SCT). Since 1971, numerous cases of DCL have been reported, but the detailed mechanisms of DCL are still unclear. A patient with jumping translocations (JTs) of 1q in umbilical cord blood donor cell-derived myelodysplastic syndrome (MDS), which likely occurred due to genetic alterations of TET2 and ASXL1 after cord blood transplantation (CBT), was examined in this study. Previously reported DCL cases after CBT that focused on the cytogenetic and molecular characteristics of these patients and patient outcome were reviewed. A total of 30 cases of DCL after CBT were identified between 2005 and 2018. The median time from CBT to the development of DCL was 16 months. The number of patients with DCL who were diagnosed with acute myeloid leukemia (AML) and MDS was 19 and 8, respectively. JTs were frequently observed in 5 of 27 DCL patients who had cytogenetic abnormalities, including our patient. Molecular abnormalities were described in 7 of the cases, and the most frequent abnormality was an NPM1 mutation. Other gene mutations that were usually found in de novo MDS or AML were observed in JT-DCL after CBT. From these results, chromosomal abnormalities such as JTs that occur subsequent to genetic alterations were seemed an important mechanisms underlying DCL onset in patients after CBT. Further molecular analyses regarding the genetic alterations of JTs are required to understand the pathogenesis of umbilical cord blood-derived JT-DCL.
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Werner syndrome (WS) confers a high risk of the development of neoplasias, including hematological malignancies, and curative treatment for these malignancies is difficult to achieve. A 44-year-old man with myelodysplastic syndrome was admitted to our hospital. He was diagnosed with mutation-proven WS. He underwent cord blood transplantation (CBT) following fludarabine, busulfan, and melphalan administration. A chimerism analysis of his marrow blood on day 62 showed a donor pattern >95%, which confirmed engraftment. The patient lived for 15 months while maintaining remission of MDS without treatment-related toxicity. Our case shows that CBT can be a treatment modality for WS patients with hematological malignancies.
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Transplante de Células-Tronco de Sangue do Cordão Umbilical , Síndromes Mielodisplásicas/terapia , Síndrome de Werner/terapia , Adulto , Antineoplásicos/uso terapêutico , Humanos , Masculino , Síndromes Mielodisplásicas/etiologia , Transplante Homólogo , Resultado do Tratamento , Síndrome de Werner/complicaçõesRESUMO
We herein describe the case of a 60-year-old man with a history of Behçet's disease and myelodysplastic syndrome who received cord blood transplantation (CBT). The patient was given anti-thymocyte globulin conditioning and tacrolimus to prevent graft-versus-host disease. Two months after CBT, his blood Tac concentration measured by an antibody-conjugated magnetic immunoassay (ACMIA) was found to have increased >4-fold, even after the Tac treatment was stopped. This false response was caused by the interference of endogenous heterophilic antibodies with ACMIA. Therefore, physicians must be aware of possible false ACMIA results for patients with a history of autoimmune disease and/or treated by xenogeneic antibody therapy.