RESUMO
BACKGROUND: Whether human T-lymphotropic virus type 1 (HTLV-1) carriers can develop sufficient humoral immunity after coronavirus disease 2019 (COVID-19) vaccination is unknown. METHODS: To investigate humoral immunity after COVID-19 vaccination in HTLV-1 carriers, a multicenter, prospective observational cohort study was conducted at five institutions in southwestern Japan, an endemic area for HTLV-1. HTLV-1 carriers and HTLV-1-negative controls were enrolled for this study from January to December 2022. During this period, the third dose of the COVID-19 vaccine was actively administered. HTLV-1 carriers were enrolled during outpatient visits, while HTLV-1-negative controls included health care workers and patients treated by participating institutions for diabetes, hypertension, or dyslipidemia. The main outcome was the effect of HTLV-1 infection on the plasma anti-COVID-19 spike IgG (IgG-S) titers after the third dose, assessed by multivariate linear regression with other clinical factors. RESULTS: We analyzed 181 cases (90 HTLV-1 carriers, 91 HTLV-1-negative controls) after receiving the third dose. HTLV-1 carriers were older (median age 67.0 vs. 45.0 years, p < 0.001) and more frequently had diabetes, hypertension, or dyslipidemia than did HTLV-1-negative controls (60.0% vs. 27.5%, p < 0.001). After the third dose, the IgG-S titers decreased over time in both carriers and controls. Multivariate linear regression in the entire cohort showed that time since the third dose, age, and HTLV-1 infection negatively influenced IgG-S titers. After adjusting for confounders such as age, or presence of diabetes, hypertension, or dyslipidemia between carriers and controls using the overlap weighting propensity score method, and performing weighted regression analysis in the entire cohort, both time since the third dose and HTLV-1 infection negatively influenced IgG-S titers. CONCLUSIONS: The humoral immunity after the third vaccination dose is impaired in HTLV-1 carriers; thus, customized vaccination schedules may be necessary for them.
Assuntos
COVID-19 , Diabetes Mellitus , Dislipidemias , Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Hipertensão , Humanos , Idoso , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Imunidade Humoral , Estudos Prospectivos , Vacinação , Imunoglobulina G , Anticorpos AntiviraisRESUMO
Essential thrombocythemia (ET) cases without canonical JAK2, CALR, or MPL mutations, that is, triple-negative (TN) ET, have been found in 10%-20% of ET cases. Owing to the limited number of TN ET cases, its clinical significance remains unclear. This study evaluated TN ET's clinical characteristics and identified novel driver mutations. Among 119 patients with ET, 20 (16.8%) had no canonical JAK2/CALR/MPL mutations. Patients with TN ET tended to be younger and had lower white blood cell counts and lactate dehydrogenase values. We identified putative driver mutations in 7 (35%): MPL S204P, MPL L265F, JAK2 R683G, and JAK2 T875N were previously reported as candidate driver mutations in ET. Moreover, we identified a THPO splicing site mutation, MPL*636Wext*12, and MPL E237K. Four of the seven identified driver mutations were germline. Functional studies on MPL*636Wext*12 and MPL E237K revealed that they are gain-of-function mutants that increase MPL signaling and confer thrombopoietin hypersensitivity with very low efficiency. Patients with TN ET tended to be younger, although this was thought to be due to the inclusion of germline mutations, hereditary thrombocytosis. Accumulating the genetic and clinical characteristics of noncanonical mutations may help future clinical interventions in TN ET and hereditary thrombocytosis.
Assuntos
Trombocitemia Essencial , Trombocitose , Humanos , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/genética , Receptores de Trombopoetina/genética , Receptores de Trombopoetina/metabolismo , Calreticulina/genética , Mutação , Janus Quinase 2/genética , Janus Quinase 2/metabolismoRESUMO
Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma with a poor prognosis when treated with chemotherapy alone; therefore, allogeneic stem cell transplantation is a consideration. We attempted cord blood transplantation (CBT) using a reduced-intensity conditioning regimen without total body irradiation (non-TBI-RIC) to allow for the best possible timing of transplantation and improve survival outcomes, particularly in older patients. Forty-eight patients (27 male, 21 female) underwent CBT using fludarabine (Flu) 125 mg/m2 and melphalan (Mel) 140 mg/m2 as pre-transplant conditioning. The median age was 32 years (range 44-72), and 21 patients were in complete remission (CR) at the time of CBT. The median duration to neutrophil engraftment (NE) was 19.5 days (range 15-50), with a cumulative incidence of NE of 86.7% at day 50 after CBT. The 1- and 3-year overall survival (OS) rates were 40.4% and 37.7%, respectively. The 3-year OS rate in CR patients was 60.8%, compared with 18.8% in non-CR patients. In ATLL patients, CBT with non-TBI-RIC using Flu/Mel is a promising treatment strategy.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Leucemia-Linfoma de Células T do Adulto/mortalidade , Leucemia-Linfoma de Células T do Adulto/terapia , Melfalan/administração & dosagem , Condicionamento Pré-Transplante , Vidarabina/análogos & derivados , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Vidarabina/administração & dosagemAssuntos
Proteínas de Neoplasias/sangue , Leucemia-Linfoma Linfoblástico de Células T Precursoras/sangue , Receptores de Interleucina-2/sangue , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/classificação , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Prognóstico , Estudos Retrospectivos , Risco , SolubilidadeRESUMO
Hepatic sinusoidal obstruction syndrome (SOS), a serious complication that mainly occurs after hematopoietic-stem cell transplantation (HSCT), is caused by damage to the sinusoidal endothelial cells after the obstruction of the sinusoid. Recently, hepatic SOS was reported to occur after non-HSCT chemotherapies. This report describes a patient who experienced hepatic SOS after non-HSCT chemotherapy for non-Hodgkin lymphoma. A liver biopsy showed the slight dilatation of the hepatic sinusoid, which may be indicative of hepatic SOS. Hepatic SOS should be included in the differential diagnosis of patients with severe liver injury following the administration of chemotherapy regimens that are toxic to the vascular endothelial cells.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hepatopatia Veno-Oclusiva/induzido quimicamente , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Evolução Fatal , Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva/diagnóstico por imagem , Hepatopatia Veno-Oclusiva/patologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Fibrosis is characterized by extracellular matrix (ECM) remodeling and stiffening. However, the functional contribution of tissue stiffening to noncancer pathogenesis remains largely unknown. Fibronectin (Fn) is an ECM glycoprotein substantially expressed during tissue repair. Here we show in advanced chronic liver fibrogenesis using a mouse model lacking Fn that, unexpectedly, Fn-null livers lead to more extensive liver cirrhosis, which is accompanied by increased liver matrix stiffness and deteriorated hepatic functions. Furthermore, Fn-null livers exhibit more myofibroblast phenotypes and accumulate highly disorganized/diffuse collagenous ECM networks composed of thinner and significantly increased number of collagen fibrils during advanced chronic liver damage. Mechanistically, mutant livers show elevated local TGF-ß activity and lysyl oxidase expressions. A significant amount of active lysyl oxidase is released in Fn-null hepatic stellate cells in response to TGF-ß1 through canonical and noncanonical Smad such as PI3 kinase-mediated pathways. TGF-ß1-induced collagen fibril stiffness in Fn-null hepatic stellate cells is significantly higher compared with wild-type cells. Inhibition of lysyl oxidase significantly reduces collagen fibril stiffness, and treatment of Fn recovers collagen fibril stiffness to wild-type levels. Thus, our findings indicate an indispensable role for Fn in chronic liver fibrosis/cirrhosis in negatively regulating TGF-ß bioavailability, which in turn modulates ECM remodeling and stiffening and consequently preserves adult organ functions. Furthermore, this regulatory mechanism by Fn could be translated for a potential therapeutic target in a broader variety of chronic fibrotic diseases.
Assuntos
Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Animais , Disponibilidade Biológica , Tetracloreto de Carbono , Doença Crônica , Colágeno/metabolismo , Fibronectinas/deficiência , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Fígado/enzimologia , Fígado/patologia , Fígado/fisiopatologia , Fígado/ultraestrutura , Cirrose Hepática/fisiopatologia , Camundongos , Mutação/genética , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Proteína-Lisina 6-Oxidase/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
Standardized treatments for indolent B cell lymphoma primarily consisting of follicular lymphoma (FL) and for mantle cell lymphoma (MCL) have yet to be established. Here the Hokuriku Hematology Oncology Study Group conducted a multicenter prospective study to investigate the efficacy and safety of a combination regimen of rituximab, cladribine, mitoxantrone, and dexamethasone (R-CMD) in indolent B cell lymphoma and MCL. A total of 33 CD20-positive patients who received care between January 2008 and August 2011 were investigated. These patients' illnesses were FL (n = 21), nodal marginal zone B cell lymphoma (NMZB, n = 3), MCL (n = 3), splenic marginal zone B cell lymphoma (n = 2), hairy cell leukemia (n = 1), Waldenstrom macroglobulinemia (WM, n = 1), and lymphoplasmacytic lymphoma (LPL, n = 2). Patients received four 21-day cycles of rituximab 375 mg/m(2) (day 1), cladribine 0.10 mg/kg (days 1-3), mitoxantrone 8 mg/m(2) (day 1), and dexamethasone 8 mg/body (days 1-3), with four additional rituximab doses at 4-week intervals. Of the 33 patients, 26 achieved complete response/unconfirmed complete response, and six achieved a partial response (4 with FL, 1 with NMZB, 1 with WM). One had progressive disease (FL), and four relapsed after remission (1 with FL, 2 with MCL, 1 with LPL). R-CMD therapy was relatively convenient and effective in indolent B cell lymphoma and MCL. Nonetheless, to suppress the number and function of both B cells and T cells, comprehensive infection prevention and follow-up are necessary in the future.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cladribina , Dexametasona/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Linfoma de Célula do Manto/tratamento farmacológico , Mitoxantrona , Rituximab , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cladribina/administração & dosagem , Cladribina/efeitos adversos , Cladribina/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Feminino , Humanos , Linfoma de Células B/mortalidade , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Mitoxantrona/efeitos adversos , Mitoxantrona/uso terapêutico , Estudos Prospectivos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Rituximab/uso terapêuticoRESUMO
Several chemokines/chemokine receptors such as CXCL12, CCL3, CXCR4 and CCR1 attract multiple myelomas to specific microenvironments. In the present study, we investigated whether the CX3CL1/CX3CR1 axis is involved in the interaction of the multiple myeloma cells with their microenvironment. The expression of CX3CR1 (also known as fractalkine) was detected in three of the seven human myeloma cell lines. CX3CL1-induced phosphorylation of Akt and ERK1/2 was detected in the CX3CR1-positive cell lines, but not in the CX3CR1-negative cell lines. In addition, CX3CL1-induced cell adhesion to fibronectin and vascular cell adhesion molecule-1 (VCAM-1) in the human myeloma RPMI-8226 cell line. We also investigated whether a relationship existed between myeloma cells and osteoclasts that may function via the CX3CL1/CX3CR1 axis. Conditioned medium from CX3CL1-stimulated RPMI-8226 cells drastically increased the osteoclast differentiation. Collectively, the results from the present study support the concept of the CX3CL1-mediated activation of the progression of the multiple myeloma via CX3CR1. Thus, CX3CR1 may represent a potential therapeutic target for the treatment of multiple myeloma in a bone microenvironment.
Assuntos
Neoplasias Ósseas/genética , Quimiocina CX3CL1/biossíntese , Mieloma Múltiplo/genética , Receptores de Quimiocinas/biossíntese , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Receptor 1 de Quimiocina CX3C , Adesão Celular/genética , Diferenciação Celular/genética , Linhagem Celular Tumoral , Quimiocina CX3CL1/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Mieloma Múltiplo/patologia , Osteoclastos/metabolismo , Osteoclastos/patologia , Fosforilação , Receptores de Quimiocinas/genética , Transdução de Sinais , Microambiente Tumoral/genética , Molécula 1 de Adesão de Célula Vascular/genéticaAssuntos
Proteínas de Ciclo Celular/genética , DNA/genética , Disceratose Congênita/genética , Mutação de Sentido Incorreto , Proteínas Nucleares/genética , Adulto , Proteínas de Ciclo Celular/metabolismo , Análise Mutacional de DNA , Disceratose Congênita/metabolismo , Humanos , Masculino , Proteínas Nucleares/metabolismoRESUMO
A 54-year-old woman with suspected low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type of the eyelids underwent rituximab-containing chemotherapy. She initially responded to the rituximab therapy, but later experienced two recurrences over a 3-year period. Biopsy specimens and a review of her previous histology revealed that she had had immunoglobulin G4-related disease at the initial presentation. Although IgG4-related disease seems to respond well to rituximab therapy, long-term follow up, including disease monitoring, is needed to evaluate disease remission.
Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Imunoglobulina G/imunologia , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Doenças Autoimunes/imunologia , Feminino , Humanos , Linfoma de Zona Marginal Tipo Células B/imunologia , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , RituximabRESUMO
Progressively transformed germinal centers is a benign condition of unknown pathogenesis characterized by a distinctive variant form of reactive follicular hyperplasia in lymph nodes. We recently reported Ig G4-related disease in progressively transformed germinal centers. However, no large case series has been reported and clinicopathologic findings remain unclear. Here, we report 40 Japanese patients (28 men, 12 women; median age, 56 years) with progressively transformed germinal centers of the lymph nodes who fulfilled the histological diagnostic criteria for IgG4-related disease (IgG4(+) progressively transformed germinal centers), with asymptomatic localized lymphadenopathy involving the submandibular nodes in 24, submandibular and cervical nodes in 14, cervical nodes only in 1, and cervical and supraclavicular nodes in 1. In all, 16 (52%) of 31 examined patients had allergic disease. Histologically, the lymph nodes demonstrated uniform histological findings, namely marked follicular hyperplasia with progressively transformed germinal centers, and localization of the majority of IgG4(+) plasma cells in the germinal centers. Serum IgG4, serum IgE and peripheral blood eosinophils were elevated in 87%, 92% and 53% of examined patients, respectively. Eighteen patients subsequently developed extranodal lesions (including five who developed systemic disease), which on histological examination were consistent with IgG4-related disease. IgG4(+) progressively transformed germinal centers presents with uniform clinicopathological features of asymptomatic localized submandibular lymphadenopathy, which persists and/or relapses, and sometimes progresses to extranodal lesions or systemic disease. Nine patients were administered steroid therapy when the lesions progressed, to which all responded well. We suggest that IgG4(+) progressively transformed germinal centers should be included in the IgG4-related disease spectrum.
Assuntos
Centro Germinativo/patologia , Imunoglobulina G , Doenças Linfáticas/patologia , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
A pregnant woman was diagnosed with acute promyelocytic leukemia at 38 weeks of gestation. Induction of labor was successful, and the patient delivered a healthy male baby. Soon after delivery, she was treated with chemotherapy using all-trans-retinoic acid (ATRA). The number of white blood cells was increased on the fifth postpartum day and retinoic acid syndrome (RAS) was considered a concern. On the sixth postpartum day, remission induction chemotherapy with idarubicin and cytosine arabinoside was started. On the seventh postpartum day, massive uterine bleeding of more than 1300 mL suddenly occurred. As administration of cytotoxic agents may induce disseminated intravascular coagulation, we should take care to avoid uterine bleeding after chemotherapy in acute promyelocytic leukemia cases treated soon after delivery.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Promielocítica Aguda/complicações , Hemorragia Pós-Parto/etiologia , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Adulto , Citarabina/uso terapêutico , Feminino , Humanos , Idarubicina/uso terapêutico , Quimioterapia de Indução , Leucemia Promielocítica Aguda/tratamento farmacológico , Gravidez , Tretinoína/uso terapêuticoRESUMO
Infectious mononucleosis (IM) is a clinical syndrome caused by primary infection with Epstein-Barr virus (EBV) that is common in adolescents. In adults, particularly in elderly people, the clinical picture of IM tends to be atypical, often leading to a diagnostic challenge. Diagnosis is also complicated because infection with EBV can induce the synthesis of cross-reacting immunoglobulin M antibodies for other herpesviruses. We report an unusual case of infectious mononucleosis in a 34-year-old immunocompetent adult. Epidemiological studies indicate that the average age of primary EBV infection in developed countries is increasing. IM with atypical presentation will be a diagnostic challenge in the future as the number of EBV-naïve adults increases.
Assuntos
Anticorpos Antivirais/sangue , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/imunologia , Herpesvirus Humano 4/imunologia , Imunoglobulina M/sangue , Mononucleose Infecciosa/diagnóstico , Adulto , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Humanos , Mononucleose Infecciosa/imunologia , Mononucleose Infecciosa/virologia , MasculinoRESUMO
A patient with acute myeloid leukemia had a relapse with a myeloid sarcoma of the stomach 32 months after allogeneic bone marrow transplantation. The patient was treated with the first donor lymphocyte infusion (DLI) and one course of induction chemotherapy. Due to severe infectious complication after chemotherapy, the patient could not continue chemotherapy. Subsequently, the patient was treated with a total of 13 cycles of DLI at 1-2 month intervals. Complete remission was achieved and neither relapse nor graft versus host disease has occurred during a follow-up of more than 10 years.
Assuntos
Leucemia Mieloide Aguda/terapia , Transfusão de Linfócitos , Segunda Neoplasia Primária/terapia , Sarcoma Mieloide/terapia , Neoplasias Gástricas/terapia , Doadores de Tecidos , Adulto , Transplante de Medula Óssea , Feminino , Seguimentos , Humanos , Indução de Remissão , Transplante HomólogoRESUMO
A 47-year-old Japanese man was first admitted to our hospital for 8 days because of an asthma attack. After discharge he changed his diet. On the 12th day after his discharge, he was re-admitted to our hospital because he exhibited transient loss of consciousness with flapping tremor. His plasma ammonia level was extremely high (245 µg/dL; normal, <90 µg/dL), suggesting hepatic encephalopathy. He underwent intravenous administration of branched-chain amino acids (Aminoleban(®)) and oral administration of lactulose and kanamycin sulfate; however, the hyperammonemia did not improve. Analysis of the amino acids and citrin gene led to the diagnosis of adult-onset type II citrullinemia (CTLN2). Following this diagnosis, the carbohydrate content of his diet was mildly restricted. As a result, his plasma ammonia level markedly improved (ammonia, 40-60 µg/dL) and he became symptom-free without any medication. CTLN2 is a metabolic disorder characterized by increased plasma concentrations of citrulline and ammonia, which occurs by the failure of compensatory mechanisms associated with diet. Here, we report a case of a patient for whom a change in eating habits during his hospitalization disturbed his compensatory mechanism resulting in clinical CTLN2, which was reversed with an appropriate diet.
RESUMO
A 23-year old woman with acute biphenotypic leukemia (ABL) complained of chest pain with cough, high fever and hemoptysis during induction chemotherapy, although she had been treated with anti-biotics and micafungin. We made a clinical diagnosis of invasive pulmonary aspergillosis (IPA) based on a consolidation in the right upper lung field on a chest radiograph as well as a high level of serum beta-D-glucan (with no evidence of tuberculosis and candidiasis). We changed her treatment from micafungin to voriconazole. Later, we discovered an air-crescent sign by CT scan that supported the diagnosis of IPA. Following voriconazole treatment, clinical symptoms ceased and abnormal chest shadows improved gradually and concurrently with a recovery of neutrophils. IPA must be considered in immunocompromised patients with pulmonary infiltrates who do not respond to broad-spectrum antibiotics. Serological tests and CT findings can aid in early diagnosis of IPA, which, along with treatment for IPA, will improve clinical outcomes.