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1.
Br J Haematol ; 203(3): 468-476, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37654088

RESUMO

To determine the prevalence and clinical relevance of glycosylphosphatidylinositol-anchored protein-deficient (GPI[-]) cell populations (paroxysmal nocturnal haemoglobinuria [PNH]-type cells) in patients with acquired aplastic anaemia (AA) or myelodysplastic syndrome (MDS), we prospectively studied peripheral blood samples of 2402 patients (1075 with AA, 900 with MDS, 144 with PNH, and 283 with other anaemia) using a high-sensitivity flow cytometry assay in a nationwide multi-centre observational study. PNH-type cells were detected in 52.6% of AA and 13.7% of MDS patients. None of the 35 patients with refractory anaemia (RA) with ringed sideroblasts or the 86 patients with RA with excess of blasts carried PNH-type cells. Among the 317 patients possessing PNH-type granulocytes, the percentage of PNH-type granulocytes increased by ≥10% in 47 patients (14.8%), remained unchanged in 240 patients (75.7%), and decreased by ≥10% in 30 patients (9.5%) during 3 years of follow-up. PNH-type granulocyte expansion occurred more frequently (27.1%) in the 144 patients who originally carried PNH-type granulocytes ≥1% than in the 173 patients with PNH-type granulocytes <1% (4.6%). This study confirmed that PNH-type cells are undetectable in authentic clonal MDS patients, and the presence of ≥1% PNH-type granulocytes predicts a higher likelihood of PNH-type cell expansion than with <1% PNH-type granulocytes.

2.
Cancer Sci ; 112(3): 1123-1131, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33492746

RESUMO

BACKGROUND: Tazemetostat is a selective and orally available inhibitor of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and epigenetic regulator of cellular differentiation programs. We carried out a phase I study of tazemetostat in Japanese patients with relapsed or refractory B-cell non-Hodgkin-type lymphoma (B-NHL) to evaluate its tolerability, safety, pharmacokinetics, and preliminary antitumor activity. METHODS: Tazemetostat was given orally at a single dose of 800 mg on the first day and 800 mg twice daily (BID: total 1600 mg/d) on following days in a 28-day/cycle manner. Tazemetostat dose-limiting toxicity (DLT) was evaluated up to the end of the first treatment cycle. Archival tumor tissues were analyzed for hotspot EZH2 mutations. RESULTS: As of 15 January 2018, seven patients (four follicular lymphoma [FL] and three diffuse large B-cell lymphoma [DLBCL]) were enrolled. The median age was 73 (range, 59-85) years, and the median number of prior chemotherapy regimens was three (range, one to five). No DLT was observed (one patient was not evaluable due to early disease progression). The common treatment-related adverse events (AEs) were thrombocytopenia and dysgeusia (three patients each; 42.9%). No treatment-related serious AEs were observed. The objective response rate was 57% (4/7 patients), including responses in three of four patients with FL and one of three patients with DLBCL. An EZH2 mutation was detected in one patient with FL responding to treatment. CONCLUSIONS: Tazemetostat at 800 mg BID showed an acceptable safety profile and promising antitumor activity in Japanese patients with relapsed or refractory B-NHL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Benzamidas/efeitos adversos , Compostos de Bifenilo/efeitos adversos , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Linfoma de Células B/tratamento farmacológico , Morfolinas/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Piridonas/efeitos adversos , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas/administração & dosagem , Benzamidas/farmacocinética , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/farmacocinética , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Feminino , Humanos , Japão , Linfoma de Células B/genética , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , Morfolinas/administração & dosagem , Morfolinas/farmacocinética , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Piridonas/administração & dosagem , Piridonas/farmacocinética , Resultado do Tratamento
3.
Ann Hematol ; 100(8): 1975-1982, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33095337

RESUMO

Small populations of glycosylphosphatidylinositol-anchored protein-deficient (GPI[-]) cells accounting for up to 0.01% of total granulocytes can be accurately detected by a high-sensitivity flow cytometry (FCM) assay established by the Clinical and Laboratory Standards Institute (CLSI method) and have a prognostic value in bone marrow failure (BMF); however, the significance of GPI(-) granulocytes accounting for 0.001-0.009% of granulocytes remains unclear. To clarify this issue, we examined the peripheral blood of 21 BMF patients in whom minor (around 0.01%) populations of GPI(-) granulocytes had been previously detected by a different high-resolution FCM method (OPTIMA method, which defines ≥ 0.003% GPI(-) granulocytes as an abnormal increase) using both the CLSI and OPTIMA methods simultaneously. These two methods detected an "abnormal increase" in GPI(-) granulocytes in 10 patients (48%) and 17 patients (81%), respectively. CLSI detected 0.002-0.005% (median, 0.004%) GPI(-) granulocytes in 7 patients who were deemed positive for PNH-type cells according to the OPTIMA method, which detected 0.003-0.012% (median 0.006%) GPI(-) granulocytes. The clone sizes of GPI(-) cells detected by each assay were positively correlated (r = 0.994, p < 0.001). Of the seven patients who were judged positive for PNH-type cells by OPTIMA alone, five received immunosuppressive therapy, and all of them achieved a partial or complete response. GPI(-) granulocytes detected in BMF patients by the CLSI method should thus be considered significant, even at percentages of < 0.01%.


Assuntos
Transtornos da Insuficiência da Medula Óssea/patologia , Proteínas Ligadas por GPI/análise , Granulócitos/patologia , Hemoglobinúria Paroxística/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos da Insuficiência da Medula Óssea/diagnóstico , Serviços de Laboratório Clínico , Feminino , Hemoglobinúria Paroxística/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Cancer Sci ; 110(5): 1686-1694, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30815927

RESUMO

We evaluated the safety, efficacy, pharmacokinetics, pharmacodynamics and predictive biomarkers of tirabrutinib, a second-generation, enhanced-selectivity Bruton's tyrosine kinase inhibitor in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-cell NHL) and chronic lymphocytic leukemia (CLL). This was an open-label, multicenter, phase I study. Seventeen patients (male N = 8) with a median age of 70 years were enrolled in 4 dose cohorts (160 mg once daily [N = 3], 320 mg once daily [N = 3], 480 mg once daily [N = 4] and 300 mg twice daily [N = 7]); 4 patients had continued tirabrutinib administration as of 4 January 2018. The maximum tolerated dose was not reached. Pneumonitis (N = 1) was the dose-limiting toxicity for 300 mg twice daily. Common adverse events (AEs) were rash (35.3%) and vomiting (29.4%). Eight patients (47.1%) developed grade ≥3 AEs: neutropenia (23.5%), anemia (11.8%) and leukopenia (11.8%) were frequent. The overall response rate (≥PR) was 76.5% (13/17 patients), including 4 DLBCL patients with no CD79A/B or MYD88 mutations, and 1 CLL patient with a TP53 mutation, providing promising data for future developments. Of 16 patients with measurable lesions during the screening period, 12 showed ≥50% reductions in tumor diameter. In many patients, the tumor size decreased soon after beginning treatment. The maximum serum concentration for tirabrutinib was 611, 1220, 1280 and 886 ng/mL on Day 1 and 484, 971 1940, and 961 ng/mL on Day 28 for Cohorts 1-4, respectively. Tirabrutinib pharmacokinetics were linear, with little accumulation following multiple doses. Tirabrutinib was well tolerated and showed promising efficacy for B-cell NHL/CLL.


Assuntos
Imidazóis/administração & dosagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antígenos CD79/genética , Esquema de Medicação , Feminino , Humanos , Imidazóis/efeitos adversos , Imidazóis/farmacocinética , Japão , Leucemia Linfocítica Crônica de Células B/genética , Masculino , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/genética , Recidiva Local de Neoplasia/genética , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacocinética , Pirimidinas/efeitos adversos , Pirimidinas/farmacocinética , Resultado do Tratamento , Proteína Supressora de Tumor p53/genética
5.
Int J Clin Oncol ; 24(4): 350-358, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30392116

RESUMO

BACKGROUND: The EuroQol 5-dimension scale (EQ-5D) is one of the most frequently used preference-based quality of life (QOL) measures for health technology assessment. The 3-level version of the EQ-5D comprises a descriptive system (the EQ-5D-3L) and a visual analog scale (EQ-VAS). It remains unclear whether this five-item scale correlates with the QOL of patients with oral cancer during the perioperative period. We sought to clarify this point in the present study. METHODS: Participants were 84 patients with oral malignancies who underwent radical treatment and completed the EQ-5D-3L and Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) at regular intervals over 3 months after treatment. We analyzed the correlations between the EQ-5D-3L, EQ-VAS, and FACT-H&N, and conducted multiple regression analyses to examine how the FACT-H&N subscales relate to the EQ-5D-3L and EQ-VAS. We also investigated whether the EQ-5D-3L shows ceiling effects. RESULTS: The EQ-5D-3L and EQ-VAS were strongly correlated with the FACT-H&N (rs = 0.621 and 0.638, respectively; P < 0.01). Furthermore, the EQ-5D-3L was significantly related with all FACT-H&N subscales except for social/family well-being. Particularly, the physical well-being subscale had the strongest relationship with the EQ-5D-3L. The FACT H&N and EQ-5D-3L showed similar changes over time. The EQ-5D-3L did not have a ceiling effect statistically. CONCLUSIONS: Our results indicate that actual physical performance might be most important for cost-utility analysis, whereas the assessment of familial feelings or friendship seems less important. However, the EQ-5D-3L appears to generally correlate with the FACT-H&N of patients with oral cancer during the perioperative period. Therefore, it is reasonable to assess the cost performance of oral cancer treatment using the EQ-5D-3L in Japan.


Assuntos
Neoplasias Bucais/cirurgia , Qualidade de Vida , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/cirurgia , Indicadores Básicos de Saúde , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Estudos Prospectivos , Inquéritos e Questionários
6.
Ann Hematol ; 97(12): 2289-2297, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30039297

RESUMO

Minor populations of glycosylphosphatidylinositol-anchored protein-deficient (GPI[-]) cells in the peripheral blood may have a prognostic value in bone marrow failure (BMF). Our objective is to establish the optimal flow cytometry (FCM) assay that can discriminate GPI(-) populations specific to BMF from those of healthy individuals. To identify a cut-off that discriminates GPI(-) rare cells from GPI(+) cells, we determined a position of the borderline that separates the GPI(-) from GPI(+) cells on a scattergram by testing more than 30 healthy individuals, such that no GPI(-) dot fell into the upper left quadrant where fluorescein-labeled aerolysin (FLAER)-CD11b+ granulocytes and CD55-CD59- glycophorin A+ erythrocytes were positioned. This method allowed us to define ≥ 0.003% CD11b+FLAER- granulocytes and ≥ 0.005% glycophorin A+CD55-CD59- erythrocytes to be specific to BMF patients. Longitudinal cross-validation studies showed minimal (< 0.02%) inter-laboratory differences in the GPI(-) cell percentage. An analysis of 1210 patients with BMF revealed a GPI(-) cell population in 56.3% of patients with aplastic anemia and 18.5% of patients with myelodysplastic syndrome. The GPI(-) granulocyte percentages was 0.003-0.01% in 3.7% of patients. This FCM assay effectively identified an increase in the percentage of GPI(-) rare cells that are specific to BMF patients and allowed different laboratories to accurately detect 0.003-0.01% of pathological GPI(-) cells.


Assuntos
Anemia Aplástica , Antígenos CD/sangue , Doenças da Medula Óssea , Eritrócitos , Citometria de Fluxo/métodos , Granulócitos , Hemoglobinúria Paroxística , Anemia Aplástica/sangue , Anemia Aplástica/patologia , Doenças da Medula Óssea/sangue , Doenças da Medula Óssea/patologia , Transtornos da Insuficiência da Medula Óssea , Eritrócitos/metabolismo , Eritrócitos/patologia , Feminino , Granulócitos/metabolismo , Granulócitos/patologia , Hemoglobinúria Paroxística/sangue , Hemoglobinúria Paroxística/patologia , Humanos , Masculino
7.
Cancer Sci ; 108(5): 1007-1012, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28267244

RESUMO

Overexpression of programmed death-1 (PD-1) ligands contributes to an immunosuppressive microenvironment. Nivolumab is a PD-1-blocking antibody that inhibits the PD-1 pathway and showed good efficacy in several types of malignancy. This phase II study examined the efficacy and safety of nivolumab in 17 Japanese patients with refractory/relapsed classical Hodgkin lymphoma previously treated with brentuximab vedotin. Sixteen patients were included in efficacy analyses and 17 in safety analyses. The primary endpoint was the centrally assessed objective response rate (ORR). The study was commenced in March 2015. We report data obtained at a cutoff of 16 March 2016, at which time 11 patients were still receiving nivolumab. The median (range) duration of treatment and follow-up were 7.0 (1.4-10.6) months and 9.8 (6.0-11.1) months, respectively. All 17 patients had previously received brentuximab vedotin. The ORR was 81.3% (95% confidence interval [CI]: 54.4-96.0%; 13/16 patients), with complete remission and partial remission in 4 and 9 patients, respectively. The overall survival (OS) and progression-free survival (PFS) rates at 6 months were 100 and 60.0% (95% CI: 31.8-79.7%), respectively; the median OS and PFS were not reached. The most common adverse events (AE) were pyrexia (41.2%), pruritus (35.3%), rash (35.3%) and hypothyroidism (29.4%). Four patients (23.5%) experienced grade 3 or 4 AE, but most AE were of grade 1 or 2. In conclusion, nivolumab is a potentially effective and tolerable treatment option for Japanese patients with relapsed/refractory classical Hodgkin lymphoma previously treated with brentuximab vedotin.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Brentuximab Vedotin , Intervalo Livre de Doença , Feminino , Doença de Hodgkin/metabolismo , Humanos , Imunoconjugados/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nivolumabe , Receptor de Morte Celular Programada 1/metabolismo , Indução de Remissão/métodos
8.
Intern Med ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38403775

RESUMO

An 83-year-old man diagnosed with multiple myeloma presented with renal failure and hyperkalemia. The patient was treated with calcium polystyrene sulfonate (CPS; kalimate) for hyperkalemia. On the 10th day after starting CPS, airway obstruction due to the presence of a mass was observed, and the patient died on that same day. Autopsy revealed that the mass was located between the trachea and epiglottis and it was determined to consist of CPS-related mosaic crystals. There was a protrusion within the trachea surrounding the CPS crystals, inflammatory cells, and granulation tissue. This case suggests that CPS is associated with not only gastrointestinal complications, but also with airway complications.

9.
Intern Med ; 62(15): 2249-2252, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36476551

RESUMO

A 21-year-old woman was diagnosed with acute lymphoblastic leukemia. After the administration of intrathecal methotrexate (MTX), the patient experienced dysarthria and paralysis for one hour. Magnetic resonance imaging (MRI) performed one hour from the onset and just before symptoms disappeared revealed no abnormalities. The next day, the symptoms appeared again, and diffusion-weighed MRI revealed a high-intensity area in the left frontal lobe. The patient was diagnosed with MTX-induced encephalopathy. This case suggested that MRI performed as soon as symptoms appear might show normal findings in MTX-induced encephalopathy.


Assuntos
Encefalopatias , Leucemia-Linfoma Linfoblástico de Células Precursoras , Feminino , Humanos , Adulto Jovem , Adulto , Metotrexato/efeitos adversos , Encefalopatias/induzido quimicamente , Encefalopatias/diagnóstico por imagem , Imageamento por Ressonância Magnética , Imagem de Difusão por Ressonância Magnética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
10.
Int J Clin Oncol ; 17(6): 584-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21986632

RESUMO

BACKGROUND: Real-time quantitative polymerase chain reaction (RQ-PCR) has been widely used for molecular monitoring for patients with chronic myeloid leukemia (CML). Currently, RQ-PCR is not based on the concept of international scale (IS) in Japan; mainly because none of the domestic laboratories have obtained their own conversion factor (CF) which makes it possible to convert locally scaled BCR-ABL (BCR-ABL (L)) value to the IS (BCR-ABL (IS)). To join the global trend of molecular assessment of BCR-ABL in CML patients, we have tried to obtain a CF in Japan. METHODS: Samples from 55 patients were exchanged between the Japanese laboratory and the reference laboratory in Adelaide, and BCR-ABL and internal control gene transcripts of the samples were measured using RQ-PCR. The patient bias conversion method was used to determine the CF for the IS using the Bland and Altman method. RESULTS: The local CF in the Japanese laboratory was determined to be 0.87. Based on this CF, 0.1% BCR-ABL (IS), defined as major molecular response, becomes equivalent to 731 copy/µg RNA BCR-ABL (L). CONCLUSION: This study is the first to introduce a laboratory-specific CF for harmonizing RQ-PCR methodology for detecting BCR-ABL transcripts to Japan, which may open new windows for molecular assessment of CML patients in Japan.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Proteínas de Fusão bcr-abl/análise , Proteínas de Fusão bcr-abl/genética , Humanos , Japão , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
11.
Rinsho Ketsueki ; 53(7): 698-704, 2012 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-22975772

RESUMO

We conducted a retrospective study to evaluate outcomes and prognostic factors of newly diagnosed patients with t(8;21) acute myeloid leukemia (AML). There were 70 patients (43 men and 27 women) with a median age of 48 years old (range, 17∼76 years old). Sixty-five patients achieved complete remission (CR) after induction chemotherapy. Fifty-seven patients received consolidation chemotherapy based on the policy of not performing allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the time of first CR. Twenty-seven of the 57 patients relapsed (relapse rate, 47%). The median time from the achievement of the first CR to relapse was 307 days (96∼1,256 days). A white blood cell count of more than 25,400/µl at diagnosis was associated with a higher relapse rate than a white blood cell count of less than or equal to 25,400/µl (75% vs. 43%, P=0.04). Nineteen of the 25 relapsed patients who received re-induction therapy experienced a second CR (second CR rate, 76%). Twenty-six patients (5 with first CR, 12 with second CR, and 9 without remission) received allo-HSCT. The five-year overall survival and disease-free survival rates were 61% and 45%, respectively. Patients with t(8;21) AML had a high CR rate, but about half of them relapsed. However, this report could not show prognostic factors for the identification of patients who should receive allo-HSCT at the time of their first CR.


Assuntos
Cromossomos Humanos Par 21/genética , Cromossomos Humanos Par 8/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Translocação Genética , Adolescente , Antimetabólitos Antineoplásicos/administração & dosagem , Citarabina/administração & dosagem , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/mortalidade , Quimioterapia de Manutenção , Masculino , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Resultado do Tratamento
12.
IJU Case Rep ; 5(3): 191-194, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35509775

RESUMO

Introduction: Intravascular large B-cell lymphoma is a rare and aggressive type of extranodal large B-cell lymphoma. Although intravascular large B-cell lymphoma can invade various organs, renal involvement has been rarely reported. Synchronous occurrence of intravascular lymphoma with renal cell carcinoma is extremely rare. We herein report a case of intravascular large B-cell lymphoma in a renal cell carcinoma incidentally detected by robot-assisted partial nephrectomy. Case presentation: A 69-year-old female with recurrent fever lasting 4 years underwent robot-assisted partial nephrectomy for small renal cell carcinoma. Histological findings led to the diagnosis of intravascular large B-cell lymphoma, which involved the normal tissue of right kidney as well as clear cell renal cell carcinoma. She received six cycles of chemotherapy without major complications and achieved complete remission. Conclusion: We encountered a rare case of synchronous intravascular lymphoma with renal cell carcinoma.

13.
Clin Chim Acta ; 489: 249-253, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30165034

RESUMO

BACKGROUND: This study aimed to develop a simple and inexpensive method using the complete blood count (CBC) and differentials to screen for chronic myeloid leukemia (CML). METHODS: The receiver operating characteristic (ROC) curves of each CBC parameter, differential and the neutrophil alkaline phosphatase (NAP) score using CML and non-CML cases were generated to determine effective cut-off values. They were applied to the review of randomly-selected 45,608 samples for validation. RESULTS: The leukocyte count showed the highest area under the ROC curve (AUC) value (0.909) among the CBC parameters. In the absolute counts of differentials, the AUC was the highest in basophils (0.982), followed by immature granulocytes (IGs) (0.975), which had cut-off values of 0.43 × 109/L and 0.46 × 109/L, respectively. The AUC of the NAP score was 0.963 at a cut-off value 122. In the validation, the absolute basophil counts were elevated in 280 samples from 96 cases, including 22 CML cases. In contrast, the absolute IG counts were elevated in 1310 samples from 516 cases, including only 17 CML cases. Three newly-diagnosed CML cases whose data were analyzed sequentially at the CML onset consistently met the basophil criteria before the IG criteria. CONCLUSIONS: The absolute basophil count is effective for screening for CML.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Programas de Rastreamento/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Contagem de Células Sanguíneas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Adulto Jovem
14.
J Clin Exp Hematop ; 59(1): 34-39, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30918142

RESUMO

Composite lymphoma (CL) is defined as the occurrence of two distinct types of lymphoma within the same patient. Most cases of CL involve Hodgkin and non-Hodgkin lymphomas or two distinct types of B-cell lymphomas; true CL is a composite B-cell and T-cell lymphoma, and is rare. We herein report a case involving concurrent extranodal NK/T-cell lymphoma, nasal-type and diffuse large B-cell lymphoma, which has not been previously reported. As the mechanisms and treatments of composite B-cell and T-cell lymphomas are unclear, further studies are required to improve the prognosis.


Assuntos
Linfoma Composto/patologia , Linfoma Extranodal de Células T-NK/patologia , Linfoma Difuso de Grandes Células B/patologia , Neoplasias Nasais/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Invasividade Neoplásica
15.
Digestion ; 77(2): 73-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18354254

RESUMO

BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is associated with the cytokine response and dysregulation of the cytokine network. Gene polymorphisms of proinflammatory cytokines are associated with several diseases including ITP. Recently, the successful eradication of Helicobacter pylori has been reported to improve the platelet counts in some patients with ITP. The aim of this study was to elucidate the relationship between cytokine gene polymorphisms and platelet recovery in ITP patients after the eradication of H. pylori. MATERIALS AND METHODS: Gastric H. pylori infection was confirmed using a culture method or specific IgG antibodies against H. pylori in the serum. Thirty-six adult H. pylori-positive ITP patients received antibiotic therapy for H. pylori. The response to treatment was defined as complete response (CR) if the platelet count was above 150 x 10(3)/microl and partial response (PR) if the platelet count increased by more than 50 x 10(3)/mul above the pretreatment count. Genomic DNA was extracted from peripheral blood and polymorphisms in IL-1B (-31, -511), IL-1RN (long or short), TNFA (-308) and TNFB (+252) were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Of the 36 ITP patients, twenty patients (responders) exhibited a platelet response after successful H. pylori eradication therapy, but the other patients (nonresponders) did not. There were no statistical differences in the frequencies of polymorphisms in IL-1B, IL-1RN and TNFA genes between responders and nonresponders. In contrast, the frequency of responders in ITP patients with the TNFB G/G or G/A genotype was significantly higher (69.6%) than that with the TNFB A/A genotype (30.8%). CONCLUSION: The TNFB (+252) G/G or G/A genotype may therefore be a good predictor of platelet recovery in ITP patients after the eradication of H. pylori.


Assuntos
Antibacterianos/uso terapêutico , Citocinas/genética , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/imunologia , Idoso , Antígenos de Bactérias/sangue , Proteínas de Bactérias/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Genótipo , Infecções por Helicobacter/imunologia , Humanos , Imunoglobulina G/sangue , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1beta/genética , Linfotoxina-alfa/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Púrpura Trombocitopênica Idiopática/microbiologia , Indução de Remissão , Fator de Necrose Tumoral alfa/genética
16.
Exp Hematol ; 35(12): 1872-83, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17923243

RESUMO

OBJECTIVE: Hematopoietic stem cells (HSCs) consist of heterogenous subpopulations, one of which is CD34(-) HSCs. Recent development of successful engraftment by intra-bone marrow transplantation revealed severe combined immunodeficiency (scid) mouse-repopulating cell (SRC) activity in human CD34(-) cord blood (CB) cells. On the other hand, CD34(-) cells from bone marrow (BM) cells remain relatively undefined. Here, we investigated pre-SRC populations in human BM CD34(-) cells and the effect of the niche-related factor, angiopoietin-1, on them. METHODS: Two populations in BM CD34(-) cells (namely M cells and S cells) were purified by flow cytometry. Then, they were cocultured with six growth factors on the hematopoietic-supportive mouse BM stromal cell line, HESS-5 or AHESS-5 that were engineered to produce human angiopoietin-1, because we detected Tie2 expression on M cells and S cells. Cultured cells were assessed for their in vitro and in vivo hematopietic activities. RESULTS: After 7 days in coculture, AHESS-5 was stronger more effective than HESS-5 in converting M and S cells to CD34(+) cells (M cells: 67.4% vs 17.5%, n =6, p < 0.001) (S cells: 42.3% vs 2.3%, n = 6, p < 0.001). Furthermore, both M and S cells were able to engraft in immunodeficient mice after they were cocultured on AHESS-5. CONCLUSIONS: Results suggest that angiopoietin-1 supports SRC activities in human CD34(-) BM cells, as murine studies demonstrated. Furthermore, identification of previously undetected subpopulations of BM CD34(-) HSCs unveils heterogenous components in the stem cell pool.


Assuntos
Angiopoietina-1/fisiologia , Antígenos CD34/imunologia , Células da Medula Óssea/citologia , Hematopoese , Western Blotting , Células da Medula Óssea/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Imuno-Histoquímica
17.
Int J Hematol ; 108(5): 491-498, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30121892

RESUMO

Cytoreductive therapy is used in high-risk essential thrombocythemia (ET) to reduce risk of thrombohemorrhagic complications. Anagrelide is an orally active, quinazolone-derived platelet-lowering agent approved for first-line treatment of high-risk ET in Japan. Long-term safety and efficacy data were collected from 53 Japanese high-risk ET patients (Study 308); 41 patients who completed Study 308 entered this phase 3b, open-label extension (Study 309; NCT01467661). Reductions in mean platelet counts occurred throughout the study, from 1021.6 × 109/L (at Study 308 baseline) to 675.4 × 109/L at final assessment. At month 48 (since Study 308 enrollment), mean platelet count was 444.5 × 109/L in the 10 patients who completed 4 years of therapy. Overall, platelet counts decreased from 1088.3 × 109/L at Study 308 baseline (n = 33) to 473.5 × 109/L at final assessment (n = 31). Long-term platelet count reductions were maintained without marked changes in mean anagrelide dose. Anagrelide was generally well tolerated, with anemia (54.7%) and headache (49.1%) as the most frequent adverse events. These findings indicate that anagrelide effectively reduces platelet counts in high-risk Japanese ET patients, with titration resulting in a well-tolerated, effective and sustainable dose. In conclusion, these results support anagrelide administration to high-risk Japanese ET patients using individualized dosing strategies defined in instructions previously approved in Europe and the USA.


Assuntos
Quinazolinas/administração & dosagem , Trombocitemia Essencial/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Quinazolinas/efeitos adversos , Fatores de Risco , Trombocitemia Essencial/sangue , Trombocitemia Essencial/epidemiologia , Fatores de Tempo
18.
Clin Lymphoma Myeloma Leuk ; 18(5): 353-360.e1, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29610029

RESUMO

INTRODUCTION: We previously reported an interim analysis of the DADI (dasatinib discontinuation) trial. The results showed that 48% of patients with chronic myeloid leukemia in the chronic phase who maintained a deep molecular response (DMR) for ≥ 1 year could discontinue second- or subsequent-line dasatinib treatment safely at a median follow-up of 20 months. However, the results from longer follow-up periods would be much more useful from a clinical perspective. PATIENTS AND METHODS: The DADI trial was a prospective, multicenter trial conducted in Japan. After confirming a stable DMR for ≥ 1 year, dasatinib treatment subsequent to imatinib or nilotinib was discontinued. After discontinuation, the loss of DMR (even of 1 point) was defined as stringent molecular relapse, thereby triggering therapy resumption. The predictive factors of treatment-free remission (TFR) were analyzed. RESULTS: The median follow-up period was 44.0 months (interquartile range, 40.5-48.0 months). The estimated overall TFR rate at 36 months was 44.4% (95% confidence interval, 32.0%-56.2%). Only 2 patients developed a molecular relapse after the 1-year cutoff point. The presence of imatinib resistance was a significant risk factor for molecular relapse. Moreover, high natural killer cell and low γδ+ T-cell and CD4+ regulatory T-cell (CD25+CD127low) counts before discontinuation correlated significantly with successful therapy discontinuation. CONCLUSION: These findings suggest that discontinuation of second- or subsequent-line dasatinib after a sustained DMR of ≥ 1 year is feasible, especially for patients with no history of imatinib resistance. In addition, the natural killer cell count was associated with the TFR.


Assuntos
Antineoplásicos/uso terapêutico , Dasatinibe/uso terapêutico , Desprescrições , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Feminino , Seguimentos , Proteínas de Fusão bcr-abl/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Fatores de Risco , Resultado do Tratamento
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