RESUMEN
A 70-year-old man who developed recurrent Stage â £A1 Sézary syndrome after first-line treatment received 6 cycles of mogamulizumab treatment. After mogamulizumab treatment completion, persistent effects on peripheral blood lesions were observed. Although Sézary syndrome is a relatively uncommon cutaneous lymphoma, it is important to recognize that the effects of mogamulizumab may not be limited to the treatment course and might be sustained even after treatment completion.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Síndrome de Sézary , Neoplasias Cutáneas , Humanos , Síndrome de Sézary/tratamiento farmacológico , Masculino , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias Cutáneas/tratamiento farmacológico , RecurrenciaRESUMEN
A 72-year-old male was referred with a 2-week history of diplopia. Following magnetic resonance imaging, an area of abnormal signal intensity was observed along the lateral ventricle, without any unusual findings at other sites. Cerebrospinal fluid cytology revealed abnormal lymphocytes with atypia, which were positive for CD20 and light-chain restriction, as detected by surface marker analysis, leading to a diagnosis of primary meningeal B-cell lymphoma. The patient underwent chemoradiotherapy and achieved a remission. While meningeal lymphoma is a rare occurrence, pathological tissue biopsy is considered the gold-standard diagnostic method. However, obtaining a biopsy sample from the tumor site can be challenging. In this case report, cytology and flow cytometry played a vital role in the diagnosis of meningeal lymphoma.
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Citometría de Flujo , Neoplasias Meníngeas , Humanos , Masculino , Anciano , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/patología , Linfoma de Células B/diagnóstico , Linfoma de Células B/patología , Linfoma de Células B/diagnóstico por imagen , Quimioradioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Imagen por Resonancia Magnética , CitologíaRESUMEN
Methotrexate (MTX)-related lymphoproliferative disease (LPD) is one of the most prominent late complications associated with MTX treatment. Although MTX-related LPD exhibits a relatively high incidence of extranodal disease, the incidence of disease in a urinary bladder is very low. The present study reports the case of a patient with MTX-related LPD involving a urinary bladder mass. A 75-year-old female patient, who had been receiving MTX for ~15 years, was referred to the hospital due to fever and hematuria. A computed tomography scan revealed the thickening of the urinary bladder wall, hydronephrosis and lymph node swelling. The histopathological findings of the urinary bladder mass resulted in a diagnosis of MTX-related LPD. Although MTX withdrawal did not have any effect, the subsequent chemotherapy resulted in complete remission. Although MTX-related LPD in the bladder is rare, it is pertinent to consider MTX-related LPD when hematuria is observed during MTX therapy.
RESUMEN
When chronic lymphocytic leukemia progressed to Richter syndrome, the coexistence of small and large lymphocytes was observed as a bone marrow finding. We consider this finding to be a clue for the progression of chronic lymphocytic leukemia to Richter syndrome.
RESUMEN
BACKGROUND: Cancer-related thrombotic microangiopathy (CR-TMA) is a rare type of Coombs-negative hemolytic anemia, which is caused by malignancy and has a poor prognosis. CASE: A 76-year-old female was referred to our hospital due to Coombs-negative hemolytic anemia, which was causing fatigue and dyspnea on exertion, accompanied by schistocytosis. A bone marrow examination demonstrated bone marrow carcinomatosis, and the tumor cells were morphologically suspected to be signet-ring cell carcinoma cells. As we failed to find the primary tumor site before the patient died, she was diagnosed with CR-TMA due to bone marrow carcinomatosis of unknown primary origin. Thrombotic thrombocytopenic purpura (TTP) was rapidly ruled out based on her PLASMIC score. In addition, immunohistochemical staining of a clot section of the bone marrow and tumor marker data were useful for narrowing down the likely primary tumor site. CONCLUSION: Although CR-TMA is an extremely rare phenomenon, clinicians who suspect CR-TMA should quickly rule out TTP and decide whether to provide appropriate chemotherapy or plan for palliative care.
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Anemia Hemolítica , Carcinoma , Coagulación Intravascular Diseminada , Neoplasias Primarias Desconocidas , Neoplasias Peritoneales , Púrpura Trombocitopénica Trombótica , Microangiopatías Trombóticas , Femenino , Humanos , Anciano , Coagulación Intravascular Diseminada/etiología , Coagulación Intravascular Diseminada/complicaciones , Púrpura Trombocitopénica Trombótica/complicaciones , Púrpura Trombocitopénica Trombótica/diagnóstico , Médula Ósea , Neoplasias Primarias Desconocidas/complicaciones , Neoplasias Primarias Desconocidas/diagnóstico , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/complicaciones , Anemia Hemolítica/complicacionesRESUMEN
Human retroviruses are derived from simian ones through cross-species transmission. These retroviruses are associated with little pathogenicity in their natural hosts, but in humans, HIV causes AIDS, and human T-cell leukemia virus type 1 (HTLV-1) induces adult T-cell leukemia-lymphoma (ATL). We analyzed the proviral sequences of HTLV-1, HTLV-2, and simian T-cell leukemia virus type 1 (STLV-1) from Japanese macaques (Macaca fuscata) and found that APOBEC3G (A3G) frequently generates G-to-A mutations in the HTLV-1 provirus, whereas such mutations are rare in the HTLV-2 and STLV-1 proviruses. Therefore, we investigated the mechanism of how HTLV-2 is resistant to human A3G (hA3G). HTLV-1, HTLV-2, and STLV-1 encode the so-called antisense proteins, HTLV-1 bZIP factor (HBZ), Antisense protein of HTLV-2 (APH-2), and STLV-1 bZIP factor (SBZ), respectively. APH-2 efficiently inhibits the deaminase activity of both hA3G and simian A3G (sA3G). HBZ and SBZ strongly suppress sA3G activity but only weakly inhibit hA3G, suggesting that HTLV-1 is incompletely adapted to humans. Unexpectedly, hA3G augments the activation of the transforming growth factor (TGF)-ß/Smad pathway by HBZ, and this activation is associated with ATL cell proliferation by up-regulating BATF3/IRF4 and MYC. In contrast, the combination of APH-2 and hA3G, or the combination of SBZ and sA3G, does not enhance the TGF-ß/Smad pathway. Thus, HTLV-1 is vulnerable to hA3G but utilizes it to promote the proliferation of infected cells via the activation of the TGF-ß/Smad pathway. Antisense factors in each virus, differently adapted to control host cellular functions through A3G, seem to dictate the pathogenesis.
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Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto , Humanos , Línea Celular , Virulencia , Virus Linfotrópico T Tipo 1 Humano/metabolismo , Leucemia-Linfoma de Células T del Adulto/genética , Provirus/genética , Factor de Crecimiento Transformador beta/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Desaminasa APOBEC-3G/genéticaRESUMEN
Human T-cell leukemia virus type 1 (HTLV-1) establishes chronic infection in humans and induces a T-cell malignancy called adult T-cell leukemia-lymphoma (ATL) and several inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Persistent HTLV-1 infection is established under the pressure of host immunity, and therefore the immune response against HTLV-1 is thought to reflect the status of the disease it causes. Indeed, it is known that cellular immunity against viral antigens is suppressed in ATL patients compared to HAM/TSP patients. In this study, we show that profiling the humoral immunity to several HTLV-1 antigens, such as Gag, Env, and Tax, and measuring proviral load are useful tools for classifying disease status and predicting disease development. Using targeted sequencing, we found that several carriers whom this profiling method predicted to be at high risk for developing ATL indeed harbored driver mutations of ATL. The clonality of HTLV-1-infected cells in those carriers was still polyclonal; it is consistent with an early stage of leukemogenesis. Furthermore, this study revealed significance of anti-Gag proteins to predict high risk group in HTLV-1 carriers. Consistent with this finding, anti-Gag cytotoxic T lymphocytes (CTLs) were increased in patients who received hematopoietic stem cell transplantation and achieved remission state, indicating the significance of anti-Gag CTLs for disease control. Our findings suggest that our strategy that combines anti-HTLV-1 antibodies and proviral load may be useful for prediction of the development of HTLV-1-associated diseases.
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Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto , Paraparesia Espástica Tropical , Adulto , Humanos , Virus Linfotrópico T Tipo 1 Humano/genética , Provirus/genética , Biomarcadores , Carga ViralRESUMEN
IMPORTANCE: The World Health Organization estimated that 5-10 million people are infected with human T-cell leukemia virus type 1 (HTLV-1). This number is likely to be underestimated because reliable endemic data are available for only approximately 1.5 billion people worldwide. The point-of-care test is a powerful tool for the easy and quick detection of infections without the requirement for expensive instruments and laboratory equipment. Espline HTLV-I/II, a newly developed rapid immunochromatographic antibody test that was evaluated in this study, might significantly advance our understanding of the global epidemiology of HTLV-1 infection.
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Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Humanos , Infecciones por HTLV-I/diagnóstico , Infecciones por HTLV-I/epidemiologíaRESUMEN
A 72-year-old male patient, who had been on chemotherapy for the treatment of IgG-λ multiple myeloma, presented an enlargement of the testis 3 years and 5 months after the diagnosis. High orchiectomy was then performed, leading to the diagnosis of plasmacytoma. Due to residual disease, treatment with a combination of isatuximab and dexamethasone was initiated. The patient is currently under follow-up without recurrence. While testicular tumors are difficult to diagnose by imaging studies alone and extramedullary plasmacytomas rarely occur in the testis, pathological assessment is critical for treatment planning.
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Mieloma Múltiple , Plasmacitoma , Neoplasias Testiculares , Masculino , Humanos , Anciano , Plasmacitoma/cirugía , Mieloma Múltiple/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/cirugía , Neoplasia ResidualRESUMEN
Donor-derived platelets are used to treat or prevent hemorrhage in patients with thrombocytopenia. However, â¼5% or more of these patients are complicated with alloimmune platelet transfusion refractoriness (allo-PTR) due to alloantibodies against HLA-I or human platelet antigens (HPA). In these cases, platelets from compatible donors are necessary, but it is difficult to find such donors for patients with rare HLA-I or HPA. To produce platelet products for patients with aplastic anemia with allo-PTR due to rare HPA-1 mismatch in Japan, we developed an ex vivo good manufacturing process (GMP)-based production system for an induced pluripotent stem cell-derived platelet product (iPSC-PLTs). Immortalized megakaryocyte progenitor cell lines (imMKCLs) were established from patient iPSCs, and a competent imMKCL clone was selected for the master cell bank (MCB) and confirmed for safety, including negativity of pathogens. From this MCB, iPSC-PLTs were produced using turbulent flow bioreactors and new drugs. In extensive nonclinical studies, iPSC-PLTs were confirmed for quality, safety, and efficacy, including hemostasis in a rabbit model. This report presents a complete system for the GMP-based production of iPSC-PLTs and the required nonclinical studies and thus supports the iPLAT1 study, the first-in-human clinical trial of iPSC-PLTs in a patient with allo-PTR and no compatible donor using the autologous product. It also serves as a comprehensive reference for the development of widely applicable allogeneic iPSC-PLTs and other cell products that use iPSC-derived progenitor cells as MCB.
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Antígenos de Plaqueta Humana , Trasplante de Células Madre Hematopoyéticas , Células Madre Pluripotentes Inducidas , Trombocitopenia , Animales , Humanos , Conejos , Transfusión de Plaquetas/efectos adversos , Células Madre Pluripotentes Inducidas/metabolismo , Plaquetas/metabolismo , Trombocitopenia/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
BACKGROUND AND CASE: We herein present a case of the co-occurrence of JAK2-mutated essential thrombocythemia (ET) with chronic lymphocytic leukemia (CLL) harboring the recurrent and rare whole-arm translocation, der(8;17)(q10;q10). The co-existence of lymphoproliferative neoplasms and myeloproliferative neoplasms is suggested to be a rare event. Under this condition, the lymphoproliferative disorder presents a clinically indolent course with a low-risk biological profile. However, the present case showed aggressive disease progression, reflecting a poor prognostic factor; that is, the loss of 17p caused by the whole-arm der(8;17)(q10;q10) translocation. CONCLUSION: The present case report emphasizes the importance of considering the involvement of a genetically poor prognostic factor, regardless of the co-occurrence of CLL and ET.
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Leucemia Linfocítica Crónica de Células B , Trombocitemia Esencial , Humanos , Janus Quinasa 2/genética , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/genética , Trombocitemia Esencial/complicaciones , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/genética , Translocación GenéticaAsunto(s)
Cromosomas Humanos Par 14 , Cromosomas Humanos Par 20 , Eliptocitosis Hereditaria/diagnóstico , Eliptocitosis Hereditaria/etiología , Eritrocitos/patología , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/genética , Translocación Genética , Cariotipo Anormal , Anciano de 80 o más Años , Humanos , Masculino , Síndromes Mielodisplásicos/diagnóstico , FenotipoRESUMEN
We report the case of an 84-year-old man who developed primary diffuse large B-cell lymphoma of the testes during the course of mycosis fungoides treated with topical medication. He was referred to our hospital due to bilateral testicular masses, and bilateral high orchiectomy was performed. A pathological diagnosis of diffuse large B-cell lymphoma was made after an examination of the surgical specimen. Rituximab-combined miniCHOP chemotherapy with prophylactic intrathecal injection resulted in complete remission without recurrence 1 year after diagnosis. People with mycosis fungoides are known to be at a higher risk of secondary malignancies than healthy individuals; hence, a pathological examination is important to confirm the diagnosis.
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Linfoma de Células B Grandes Difuso , Micosis Fungoide , Neoplasias Cutáneas , Anciano de 80 o más Años , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Micosis Fungoide/tratamiento farmacológico , Rituximab , Neoplasias Cutáneas/tratamiento farmacológico , TestículoRESUMEN
Although isolated trisomy 9, a form of chromosome aneuploidy, is rare in acute myeloid leukemia (AML), up to 30 cases of AML involving isolated trisomy 9 have been reported to date. We report the case of a 77-year-old female with AML, in which trisomy 9 was detected as an isolated aberration. In addition, the patient's bone marrow displayed so-called sea-blue histiocytosis. The accumulation of further cases of isolated trisomy 9-harboring AML involving sea-blue histiocytosis is necessary to determine whether the coexistence of these findings is pathognomonic or a coincidence.