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1.
Int J Hematol ; 118(6): 731-736, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37747583

RESUMO

Pre-exposure prophylaxis with tixagevimab/cilgavimab was considered a useful strategy to protect immunocompromised patients from COVID-19 based on the phase 3 PROVENT trial conducted between November 2020 and March 2021. However, after late 2021, the dominant substrains of COVID-19 changed to Omicron substrains, which showed resistance to tixagevimab/cilgavimab. Therefore, it is important to re-evaluate the real-world efficacy of tixagevimab/cilgavimab for the prevention of COVID-19 in the Omicron era. To this end, we retrospectively evaluated the efficacy and safety of tixagevimab/cilgavimab prophylaxis for COVID-19 during the Omicron BA.5 wave in Japan. A total of 240 consecutive patients with hematologic malignancies received tixagevimab/cilgavimab at our institution from October 18, 2022, to January 31, 2023. Among them, the cumulative incidence of COVID-19 at 90 days was 6.4%. A total of 10/14 (71.4%) had mild infection, and 4/14 (28.5%) had severe infection. No patient died due to COVID-19. Adverse events consisted of deep vein thrombosis in 2 patients. Our analysis indicated that pre-exposure prophylaxis with tixagevimab/cilgavimab might have clinical effectiveness in reducing the severity of COVID-19 in Japanese HM patients, even in the Omicron BA.5 surge. It also suggested that tixagevimab/cilgavimab may be associated with cardiovascular complications.


Assuntos
COVID-19 , Profilaxia Pré-Exposição , Humanos , COVID-19/prevenção & controle , Japão/epidemiologia , Estudos Retrospectivos , Ensaios Clínicos Fase III como Assunto
2.
Rinsho Ketsueki ; 64(2): 83-90, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-36990737

RESUMO

Hypokalemia is common in allogeneic hematopoietic stem cell transplantation (allo-HCT) patients and is associated with non-relapse mortality (NRM). Therefore, it is extremely important to replace potassium adequately. We evaluated the safety and efficacy of potassium replacement therapy by retrospectively analyzing the incidence and severity of hypokalemia in 75 patients who received allo-HCT at our institution. 75% of patients developed hypokalemia during the allo-HSCT, and 44% of patients had grade 3-4 levels of hypokalemia. NRM was significantly higher in patients with grade 3-4 hypokalemia than in patients without severe hypokalemia (one-year NRM: 30% vs 7%, p=0.008). Although 75% of the patients required potassium replacement that exceeded the range of potassium chloride solutions package inserts in Japan, we did not experience any adverse events associated with hyperkalemia. Our current observations suggested that the Japanese package insert for potassium solution injection should be revised for potassium needs.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Hipopotassemia , Humanos , Estudos Retrospectivos , Potássio , Hipopotassemia/etiologia , Transplante Homólogo/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
3.
Int J Hematol ; 116(4): 544-552, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35538304

RESUMO

We analyzed the incidence of bone marrow fibrosis in 91 newly diagnosed Japanese multiple myeloma (MM) patients and evaluated the impact of fibrosis on clinical characteristics and therapeutic outcomes. Thirty-four (37%) patients had greater than grade 1 bone marrow fibrosis. The presence of bone marrow fibrosis did not affect laboratory data, the percentage of plasma cells in bone marrow or cytogenetic findings. It also had no significant effect on response to initial treatment, engraftment after autologous hematopoietic stem cell transplantation or overall survival. Interestingly, the incidence of extramedullary disease at diagnosis was significantly higher in patients with bone marrow fibrosis (p = 0.006). Analysis of biological characteristics of MM cells revealed that expression of CD49e, an alpha5/beta1 integrin, was downregulated in MM cells derived from patients with bone marrow fibrosis (p = 0.026). When seven of the original 34 patients were re-evaluated for fibrosis grading after treatment, five (71%) showed a reduction in fibrosis. Our present findings suggest that the presence of bone marrow fibrosis may predict development of extramedullary disease in MM.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Mielofibrose Primária , Fibrose , Humanos , Integrina alfa5 , Integrina beta1 , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Mielofibrose Primária/etiologia , Mielofibrose Primária/terapia
4.
Virchows Arch ; 480(5): 1101-1105, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34226971

RESUMO

We report an exceptionally rare case of mantle cell lymphoma (MCL) that transdifferentiated into sarcoma with limited neuromuscular differentiation. An 81-year-old man with t(11;14)-positive MCL was treated with rituximab and bendamustine and achieved complete remission; however, just 2 months later, the patient developed multiple systemic tumors. Pathologic studies revealed round cell sarcoma expressing synaptophysin, CD56, and myogenin without any B-cell markers. The CCND1 translocation and an identical IGL gene rearrangement were shared by both the MCL and sarcoma. Whole-exome sequencing detected 189 single nucleotide variants (SNVs) in the MCL and 205 SNVs in the sarcoma; 160 SNVs including NSD2, ATM, RB1, and TP53 mutations were shared between MCL and sarcoma cells. An additional PTPN11 mutation was specifically found in the sarcoma. These findings confirmed the shared clonal origin of MCL and sarcoma in this patient and indicated that MCL can transdifferentiate into sarcoma in rare cases.


Assuntos
Linfoma de Célula do Manto , Sarcoma , Neoplasias de Tecidos Moles , Idoso de 80 Anos ou mais , Transdiferenciação Celular , Genes de Imunoglobulinas , Humanos , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/patologia , Masculino , Mutação , Sarcoma/tratamento farmacológico , Sarcoma/genética , Neoplasias de Tecidos Moles/genética
5.
Intern Med ; 60(20): 3305-3308, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33896865

RESUMO

A 71-year-old woman with a four-year history of chronic lymphocytic leukemia (CLL) received ibrutinib as initial treatment due to progressive anemia and thrombocytopenia. Eleven months after the start of the treatments, although her cytopenia had ameliorated, she developed classic Hodgkin lymphoma, a rare form of Richter's transformation. She was successfully treated with two courses of adriamycin, vinblastin, bleomycin and dacarbazine followed by radiotherapy. In general, several clinical, genetic and molecular factors are associated with Richter's transformation. In addition, our present case suggested that ibrutinib could be a potential risk factor for Richter's transformation in CLL patients.


Assuntos
Doença de Hodgkin , Leucemia Linfocítica Crônica de Células B , Adenina/análogos & derivados , Idoso , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Piperidinas , Pirazóis , Pirimidinas/efeitos adversos
6.
Rinsho Ketsueki ; 62(3): 170-175, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33828009

RESUMO

Post-transplant lymphoproliferative disorder (PTLD) usually develops with systemic symptoms, such as fever, generalized lymphadenopathy, and elevation in the lactate dehydrogenase level. Here, we present the case of a 65-year-old female patient with PTLD localized to the colon; the patient only had mild diarrhea without systemic symptoms. She had myelodysplastic syndrome and was treated with cord blood transplantation (CBT). She had a past medical history of sigmoid colon cancer treated with colonosectomy and adjuvant chemotherapy. After CBT, she achieved complete remission and was discharged after 60 days. Further, 79 days after CBT, she presented with abdominal pain. Computed tomography scan revealed adhesive ileus. The abdominal pain was resolved in 1 day with conservative treatment, however, mild diarrhea persisted. Therefore, we performed colonoscopy and found multiple ulcerative lesions in the upper colon. A pathological examination revealed PTLD. Furthermore, elevation of EBV-DNA in the blood was also confirmed. There was no detectable lesion on positron emission tomography-computed tomography (PET-CT) outside the colon; thus, we diagnosed PTLD localized into the colon that was successfully treated with rituximab. Our present experience suggests that it might be important to perform endoscopy and monitoring of EBV-DNA for early detection of PTLD, especially localized in the gastrointestinal tract.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Infecções por Vírus Epstein-Barr , Transtornos Linfoproliferativos , Idoso , Colo , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Diarreia/etiologia , Diarreia/terapia , Detecção Precoce de Câncer , Infecções por Vírus Epstein-Barr/complicações , Feminino , Humanos , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
7.
Rinsho Ketsueki ; 61(2): 110-115, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32147609

RESUMO

Angioimmunoblastic T-cell lymphoma (AITL) is frequently associated with immunological abnormalities, such as hypergammaglobulinemia, autoimmune cytopenia, and the presence of various autoantibodies. Few reports on AITL have also described the development of myelofibrosis resulting from the invasion of lymphoma cells that produced various cytokines, including TGF-ß. Interestingly, recent studies demonstrated that autoimmunity can directly cause autoimmune myelofibrosis (AIMF). Usually, bone marrow fibrosis associated with AIMF is rapidly improved by treatment. Here, we describe our experience with a case of AITL complicated with the presence of numerous autoimmune abnormalities, including positive Coombs, anti-nuclear antibody, anti-ds-DNA antibody, anti-phospholipid antibody, and cold agglutinin tests. The patient presented with severe bone marrow fibrosis (MF-3) at the initial diagnosis. After two courses of the CHASE therapy, myelofibrosis rapidly disappeared, and the autoimmune abnormalities were ameliorated. These findings suggest that the bone marrow fibrosis observed in this case was partly attributable to an AIMF-like mechanism.


Assuntos
Linfadenopatia Imunoblástica , Linfoma de Células T , Mielofibrose Primária , Autoanticorpos , Fibrose , Humanos
9.
Intern Med ; 58(17): 2561-2568, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31118384

RESUMO

Metastasis of cancer cells to the bone marrow is relatively rare, despite being one of the most important causes of myelosuppression in patients with solid tumours. A bone marrow examination via a biopsy is the standard method of diagnosing cancer cell invasion into the bone marrow. However, it is sometimes challenging to distinguish neuroendocrine carcinoma cells from haematopoietic cells due to their small, round shape and chromosomal abnormalities resembling haematological malignancies. We herein report a case of bone marrow invasion of small cell neuroendocrine carcinoma of the endometrium mimicking therapy-related myeloid malignancy.


Assuntos
Medula Óssea/patologia , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Pequenas/patologia , Neoplasias do Endométrio/patologia , Neoplasias Hematológicas/diagnóstico , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica
10.
Intern Med ; 57(22): 3303-3306, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-29984746

RESUMO

Coagulation abnormalities are a rare but critical complication associated with plasma cell diseases. We herein present a case of multiple myeloma (MM) with complicated coagulopathy. Initially, the patient showed severe bleeding tendency due to concomitant acquired hemophilia A and acquired von Willebrand syndrome. Interestingly, the patient also exhibited hyperactivation of factor IX. During treatment for MM, the bleeding complications were ameliorated; however, the patient had central retinal vein occlusion. All of the coagulation abnormalities were completely resolved after the complete remission of MM. This case suggests that MM patients may have concomitant risks for both bleeding and thromboembolic complications.


Assuntos
Hemofilia A/complicações , Hemorragia/etiologia , Mieloma Múltiplo/complicações , Trombose/complicações , Doenças de von Willebrand/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Intern Med ; 56(17): 2335-2338, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28794380

RESUMO

The development of tumor lysis syndrome (TLS) in association with treatment for myeloproliferative neoplasms (MPNs) is relatively rare. We herein present the case of a post-polycythemia vera (PV) myelofibrosis patient with massive splenomegaly who developed laboratory TLS after treatment with ruxolitinib, a potent JAK1/JAK2 inhibitor. She also exhibited a rapid reduction of spleen volume. Our present case suggests the potential risk of TLS development after ruxolitinib treatment, particularly in patients with massive splenomegaly.


Assuntos
Transtornos Mieloproliferativos/complicações , Policitemia Vera/tratamento farmacológico , Mielofibrose Primária/complicações , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Síndrome de Lise Tumoral/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Policitemia Vera/etiologia , Pirimidinas , Baço/patologia , Resultado do Tratamento
12.
Rinsho Ketsueki ; 58(3): 228-232, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-28381690

RESUMO

Although myelofibrosis is mainly associated with myeloproliferative neoplasms (MPN), especially primary myelofibrosis (PMF), a variety of hematological malignancies, including acute myeloid leukemia, multiple myeloma and malignant lymphoma, also cause myelofibrosis with markedly varying degrees of severity. Thus, it is extremely important to accurately diagnose the underlying diseases that cause fibrosis in bone marrow. Analyses of JAK2, MPL and calreticulin gene mutations are useful for distinguishing MPN from other diseases, since 90% of MPN patients have a mutation in one of these genes. However, 10% of PMF patients do not have mutations in any of these genes, and these patients have a disease known as triple negative PMF. It is sometimes difficult to accurately distinguish triple negative PMF from secondary myelofibrosis caused by other diseases. Herein, we present a case of diffuse large B cell lymphoma (DLBCL) with bone marrow involvement, mimicking triple negative primary myelofibrosis. 18F-FDG-PET was useful for correctly diagnosing DLBCL.


Assuntos
Medula Óssea/patologia , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Mielofibrose Primária/diagnóstico por imagem , Idoso , Diagnóstico Diferencial , Fluordesoxiglucose F18 , Humanos , Linfoma Difuso de Grandes Células B/genética , Masculino , Mutação/genética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Mielofibrose Primária/genética
13.
Rinsho Ketsueki ; 56(3): 317-22, 2015 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-25876786

RESUMO

A 60-year-old woman was admitted to our hospital with anemia and thrombocytopenia. Serum testing showed platelet-associated IgG elevation and she was positive on the direct and indirect Coombs tests. Together with bone marrow examination, these findings indicated a diagnosis of Evans syndrome. At diagnosis, she also had an IgM-κ type of monoclonal gammopathy of unknown significance. Initially, we administered steroids and her hemolytic anemia showed improvement. In contrast, only transient recovery of platelet counts was observed and her platelet counts rapidly decreased after steroid dose reduction. Thus, we treated her with a TPO-agonist, romiplostim. During the clinical course, she showed gradual serum IgM elevation. We thus performed another bone marrow biopsy and diagnosed her as having Waldenström's macroglobulinemia (WM). We started treatment with rituximab for WM. Together with the serum IgM reduction, she showed marked improvement of thrombocytopenia. This is a very rare case of WM initially presenting as autoimmune hemolytic anemia and immunethrombocytopenia associated with IgG class auto-antibody. Our experience suggests the usefulness of rituximab and romiplostim for the treatment of immunethrombocytopenia associated with WM.


Assuntos
Anemia Hemolítica Autoimune/tratamento farmacológico , Anticorpos Monoclonais Murinos/uso terapêutico , Imunossupressores/uso terapêutico , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Trombocitopenia/tratamento farmacológico , Trombopoetina/uso terapêutico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/etiologia , Anticorpos Monoclonais Murinos/administração & dosagem , Combinação de Medicamentos , Feminino , Humanos , Imunossupressores/administração & dosagem , Pessoa de Meia-Idade , Receptores Fc/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Rituximab , Trombocitopenia/diagnóstico , Trombocitopenia/etiologia , Trombopoetina/administração & dosagem , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/patologia
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