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1.
Int J Clin Oncol ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38755516

RESUMO

BACKGROUND: The outcomes of relapsed or refractory acute myeloid leukemia (AML) remain poor. Although the concomitant use of granulocyte colony-stimulating factor (G-CSF) and anti-chemotherapeutic agents has been investigated to improve the antileukemic effect on AML, its usefulness remains controversial. This study aimed to investigate the effects of G-CSF priming as a remission induction therapy or salvage chemotherapy. METHODS: We performed a thorough literature search for studies related to the priming effect of G-CSF using PubMed, Ichushi-Web, and the Cochrane Library. A qualitative analysis of the pooled data was performed, and risk ratios (RRs) with confidence intervals (CIs) were calculated and summarized. RESULTS: Two reviewers independently extracted and accessed the 278 records identified during the initial screening, and 62 full-text articles were assessed for eligibility in second screening. Eleven studies were included in the qualitative analysis and 10 in the meta-analysis. A systematic review revealed that priming with G-CSF did not correlate with an improvement in response rate and overall survival (OS). The result of the meta-analysis revealed the tendency for lower relapse rate in the G-CSF priming groups without inter-study heterogeneity [RR, 0.91 (95% CI 0.82-1.01), p = 0.08; I2 = 4%, p = 0.35]. In specific populations, including patients with intermediate cytogenetic risk and those receiving high-dose cytarabine, the G-CSF priming regimen prolonged OS. CONCLUSIONS: G-CSF priming in combination with intensive remission induction treatment is not universally effective in patients with AML. Further studies are required to identify the patient cohort for which G-CSF priming is recommended.

2.
Cureus ; 16(4): e59043, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38800333

RESUMO

Background In patients with hematologic malignancies, faster species identification is particularly important in the management of bloodstream infection because of their immunocompromised and neutropenic status. In the present study, we analyzed direct species identification in patients with hematologic malignancies, and the factors that might influence the results of species identification. Methods We performed direct species identification using a Sepsityper® kit (Bruker Corporation, Billerica, Massachusetts, United States) and compared the results with a conventional method in patients with hematologic malignancies. Forty-five positive blood culture bottles containing single microorganisms from 37 patients were analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). And patients' clinical data were compared between the groups with spectral scores at acceptable and unacceptable levels. Results Direct species identification correctly identified 42 of 45 isolates and three were misidentified. While 35 of 45 isolates showed a spectral score ≥1.7 (acceptable identification), 10 isolates had a spectral score <1.7 (unacceptable identification) including three misidentified isolates. The group with a spectral score ≥1.7 had significantly lower white blood cell (p<0.01), neutrophil (p<0.01), and platelet (p<0.01) counts in addition to more frequent central venous (CV) line insertion (p=0.01). Multivariate analysis revealed that pathogen type (gram-positive or negative) and CV line insertion were associated with spectral scores. Conclusion Direct species identification using the Sepsityper kit is an upcoming approach for blood culture bottles, which were flagged as positive even in patients with hematologic malignancies when the spectral score was ≥ 1.7. Our study also indicates that direct identification is more accurate in patients with CV lines, and may be less accurate when gram-positive bacteria are detected.

3.
Int J Clin Oncol ; 29(5): 535-544, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38494578

RESUMO

Although granulocyte colony-stimulating factor (G-CSF) reduces the incidence, duration, and severity of neutropenia, its prophylactic use for acute myeloid leukemia (AML) remains controversial due to a theoretically increased risk of relapse. The present study investigated the effects of G-CSF as primary prophylaxis for AML with remission induction therapy. A detailed literature search for related studies was performed using PubMed, Ichushi-Web, and the Cochrane Library. Data were independently extracted and assessed by two reviewers. A qualitative analysis of pooled data was conducted, and the risk ratio with corresponding confidence intervals was calculated in the meta-analysis and summarized. Sixteen studies were included in the qualitative analysis, nine of which were examined in the meta-analysis. Although G-CSF significantly shortened the duration of neutropenia, primary prophylaxis with G-CSF did not correlate with infection-related mortality. Moreover, primary prophylaxis with G-CSF did not affect disease progression/recurrence, overall survival, or adverse events, such as musculoskeletal pain. However, evidence to support or discourage the use of G-CSF as primary prophylaxis for adult AML patients with induction therapy remains limited. Therefore, the use of G-CSF as primary prophylaxis can be considered for adult AML patients with remission induction therapy who are at a high risk of infectious complications.


Assuntos
Fator Estimulador de Colônias de Granulócitos , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Indução de Remissão , Guias de Prática Clínica como Assunto , Quimioterapia de Indução , Japão , Neutropenia/induzido quimicamente , Neutropenia/prevenção & controle
4.
Am J Hematol ; 99(5): 806-815, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38314662

RESUMO

This study aimed to investigate the usefulness of allogeneic stem cell transplantation (allo-SCT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) in the first complete remission (CR1) with complete molecular remission (CMR). We compared the outcomes between Ph+ALL patients who did or did not undergo allo-SCT in CR1. We included patients enrolled in the prospective clinical studies in the tyrosine kinase inhibitor era conducted by the Japan Adult Leukemia Study Group, who achieved CMR within 3 months. A total of 147 patients (allo-SCT: 101; non-SCT: 46) were eligible for this analysis. In the multivariate analyses, allo-SCT was significantly associated with both superior overall survival (OS) (adjusted hazard ratio (aHR): 0.54; 95% CI: 0.30-0.97; p = .04) and relapse-free survival (RFS) (aHR: 0.21; 95% CI: 0.12-0.38; p < .001). The 5-year adjusted OS and RFS were 73% and 70% in the allo-SCT cohort, whereas they were 50% and 20% in the non-SCT cohort. Despite the higher non-relapse mortality (aHR: 3.49; 95% CI: 1.17-10.4; p = .03), allo-SCT was significantly associated with a lower relapse rate (aHR: 0.10; 95% CI: 0.05-0.20; p < .001). In addition, allo-SCT was also associated with superior graft-versus-host disease-free, relapse-free survival (aHR: 0.43; 95% CI: 0.25-0.74; p = .002). Propensity score-matched analyses confirmed the results of the multivariate analyses. In patients who achieved CMR within 3 months, allo-SCT in CR1 had superior survival and lower relapse compared with the non-SCT cohort.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Estudos Prospectivos , Transplante Homólogo , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Resposta Patológica Completa , Estudos Retrospectivos
5.
Br J Haematol ; 204(5): 2086-2096, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38296352

RESUMO

Morphological dysplasia in haematopoietic cells, defined by a 10% threshold in each lineage, is one of the diagnostic criteria for myelodysplastic neoplasms. Dysplasia limited to the erythroid lineage has also been reported in some cases of aplastic anaemia (AA); however, its significance remains unclear. We herein examined the impact of erythroid dysplasia on immunosuppressive therapy responses and survival in AA patients. The present study included 100 eligible AA patients without ring sideroblasts. Among them, 32 had dysplasia in the erythroid lineage (AA with minimal dysplasia [mini-D]). No significant sex or age differences were observed between AA groups with and without erythroid dysplasia. In severe/very severe AA and non-severe AA patients, a response to anti-thymocyte globulin + ciclosporin within 12 months was observed in 80.0% and 60.0% of AA with mini-D and 42.9% and 90.0% of those without dysplasia, with no significant difference (p = 0.29 and p = 0.24 respectively). Overall survival and leukaemia-free survival did not significantly differ between the groups. Collectively, the present results indicate that the presence of erythroid dysplasia did not significantly affect clinical characteristics or outcomes in AA patients, suggesting that its presence in AA is acceptable. Therefore, erythroid dysplasia should not exclude an AA diagnosis.


Assuntos
Anemia Aplástica , Sistema de Registros , Humanos , Anemia Aplástica/mortalidade , Anemia Aplástica/patologia , Anemia Aplástica/tratamento farmacológico , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Adulto Jovem , Células Eritroides/patologia , Adolescente , Idoso de 80 Anos ou mais
6.
Ann Hematol ; 103(1): 307-320, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37940714

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the sole curative therapy for myelodysplastic syndrome (MDS). However, whether bridging therapy (BRT) including azacitidine (AZA) and combination chemotherapy (CCT) prior to allo-SCT should be performed is unclear. We analyzed BRT and the outcomes of patients with myelodysplastic syndrome with excess blasts (MDS-EB) who were ≤ 70 years old at the time of registration for a prospective observational study to clarify the optimal allo-SCT strategy for high-risk MDS. A total of 371 patients were included in this study. Among 188 patients (50.7%) who were considered for allo-SCT, 141 underwent allo-SCT. Among the patients who underwent allo-SCT, 64 received AZA, 29 received CCT, and 26 underwent allo-SCT without BRT as the initial treatment. Multivariate analysis identified BRT as an independent factor influencing overall survival (AZA vs. without BRT, hazard ratio [HR] 3.33, P = 0.005; CCT vs. without BRT, HR 3.82, P = 0.003). In multivariate analysis, BRT was independently associated with progression-free survival (AZA vs. without BRT: HR, 2.23; P = 0.041; CCT vs. without BRT: HR, 2.94; P = 0.010). Transplant-eligible patients with MDS-EB should undergo allo-SCT when clinically acceptable, and upfront allo-SCT without BRT may be superior to AZA or CCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Humanos , Idoso , Azacitidina/uso terapêutico , Transplante Homólogo , Aloenxertos , Estudos Retrospectivos
7.
Intern Med ; 63(6): 847-852, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-37495531

RESUMO

Essential thrombocythemia is a myeloproliferative neoplasm. Ischemic stroke is frequently the first manifestation of essential thrombocythemia. We herein report a patient with JAK2V617 mutation-positive essential thrombocythemia who developed recurrent ischemic stroke with rapid development of intracranial artery stenosis and subsequently underwent successful mechanical thrombectomy. The high JAK2V617F allele burden in our patient (58.4%) may have affected the patient's condition. We discuss similar reports in the literature and the possible pathophysiologic mechanism of large artery involvement in these patients.


Assuntos
AVC Isquêmico , Trombocitemia Essencial , Humanos , Constrição Patológica , Trombocitemia Essencial/complicações , Artérias , Infarto Cerebral , Mutação , Trombectomia , Janus Quinase 2/genética
9.
Rinsho Ketsueki ; 64(4): 271-276, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-37121771

RESUMO

We present a case of thoracic SMARCA4-deficient undifferentiated tumor that needed to be differentiated from malignant lymphoma owing to multiple lymph node swelling and marrow involvement. A 52-year-old man developed multiple lymphadenopathies along with anorexia, general fatigue, fever, and sweating 2 months prior to admission. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan revealed a mass lesion on the right upper lung, generalized lymph node swelling, and bone metastasis, indicating the presence of suspicious lung cancer; therefore, he was referred to our hospital. Malignant lymphoma was suspected at the time of admission because of elevated levels of lactate dehydrogenase (11,977 U/l) and soluble interleukin 2 receptor (2,152 U/ml) as well as marrow infiltration of large abnormal cells. On day 11, the patient died from rapid respiratory failure. Histological and immunohistochemical features of the pleural effusion cell block led to the diagnosis of thoracic SMARCA4-deficient undifferentiated tumor. Thoracic SMARCA4-deficient undifferentiated tumor was recently introduced in the 2021 World Health Organization classification of lung tumors, with most patients being young adults with a history of heavy smoking and poor prognosis. Because of the multiple lymph node swelling and marrow involvement, this undifferentiated tumor should be distinguished from malignant lymphoma.


Assuntos
Linfoma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais , DNA Helicases , Fluordesoxiglucose F18 , Linfoma/diagnóstico , Proteínas Nucleares , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fatores de Transcrição
10.
Int J Hematol ; 116(2): 228-238, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35508695

RESUMO

The hypomethylating agent azacitidine (AZA) significantly extends overall survival (OS) in patients with higher risk myelodysplastic syndromes (MDS), when compared with other conventional care regimens, including supportive care and low-dose and intensive chemotherapy. However, the effects of 5- and 7-day treatment schedules of AZA (AZA-5 and AZA-7, respectively) on the OS of MDS patients had not been compared prospectively. We started a phase 3 trial comparing the effects of AZA-7 and AZA-5 on MDS patients with refractory anemia with excess blasts (RAEB) and RAEB in transformation (RAEB-T). However, this trial was prematurely terminated because of poor recruitment. Using all data, there was no significant difference in the OS of patients between AZA-7 (92 patients) and AZA-5 (95 patients), with the 2-year OS rates of AZA-7 and AZA-5 at 36.4% and 25.8%, respectively (P = 0.293). Adverse event profiles were similar between the two groups. Interestingly, data of the centrally diagnosed RAEB and RAEB-T cases showed that AZA-7 significantly prolonged the time to leukemia transformation compared with AZA-5 (P = 0.022), confirmed by multivariate analysis. Although this trial could not provide definite evidence, the results support the use of AZA-7 for RAEB and RAEB-T. (UMIN Clinical Trials Registry UMIN000009633).


Assuntos
Anemia Refratária com Excesso de Blastos , Azacitidina , Síndromes Mielodisplásicas , Anemia Refratária com Excesso de Blastos/tratamento farmacológico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Humanos , Síndromes Mielodisplásicas/tratamento farmacológico
11.
Sensors (Basel) ; 22(4)2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-35214266

RESUMO

Various biosensors that are based on microfabrication technology have been developed as point-of-care testing devices for disease screening. The Fabry-Pérot interferometric (FPI) surface-stress sensor was developed to improve detection sensitivity by performing label-free biomarker detection as a nanomechanical deflection of a freestanding membrane to adsorb the molecules. However, chemically functionalizing the freestanding nanosheet with excellent stress sensitivity for selective molecular detection may cause the surface chemical reaction to deteriorate the nanosheet quality. In this study, we developed a minimally invasive chemical functionalization technique to create a biosolid interface on the freestanding nanosheet of a microelectromechanical system optical interferometric surface-stress immunosensor. For receptor immobilization, glutaraldehyde cross-linking on the surface of the amino-functionalized parylene membrane reduced the shape variation of the freestanding nanosheet to 1/5-1/10 of the previous study and achieved a yield of 95%. In addition, the FPI surface-stress sensor demonstrated molecular selectivity and concentration dependence for prostate-specific antigen with a dynamic range of concentrations from 100 ag/mL to 1 µg/mL. In addition, the minimum limit of detection of the proposed sensor was 2,000,000 times lower than that of the conventional nanomechanical cantilevers.


Assuntos
Técnicas Biossensoriais , Sistemas Microeletromecânicos , Neoplasias da Próstata , Biomarcadores , Técnicas Biossensoriais/métodos , Humanos , Imunoensaio/métodos , Masculino , Neoplasias da Próstata/diagnóstico
12.
Int J Hematol ; 115(6): 898-901, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35089531

RESUMO

We present the case of a 56-year-old male patient with paravertebral extramedullary hematopoiesis (EMH) secondary to myelodysplastic syndrome with ring sideroblasts and multilineage dysplasia. In a routine health checkup over 5 years prior, he presented with asymptomatic mild anemia and a posterior mediastinal mass. Pathological and cytomorphological findings of the resected paravertebral mass were similar to those of his bone marrow specimen, and included cellularity with erythroid hyperplasia, multilineage dysplastic changes, and the presence of ring sideroblasts. A concordant SF3B1 mutation was detected in both bone marrow and paravertebral mass samples, suggesting that the EMH cells were derived from the bone marrow.


Assuntos
Hematopoese Extramedular , Síndromes Mielodisplásicas , Hematopoese Extramedular/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Fosfoproteínas/genética , Fatores de Processamento de RNA/genética
13.
J Clin Exp Hematop ; 62(1): 18-24, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-34980789

RESUMO

Bendamustine is now recognized as a key drug for indolent B-cell lymphoma (iBCL), mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). Skin toxicity associated with bendamustine is one of the characteristic adverse effects. We retrospectively examined the relationship between bendamustine-associated drug rashes and disease prognosis of iBCL and MCL at our institution. Between January 2011 and August 2019, 65 patients (39 men and 26 women, median age 68, range 41-84 years) were treated with bendamustine alone (n=11, 120 mg/m2 on days 1 and 2) or a combination of rituximab and bendamustine (n=54, 90 mg/m2 on days 1 and 2). Of these patients, 47 had follicular lymphoma (FL), 10 had MCL and 8 had other iBCLs. Drug rash occurred in 27 (41.5%). Eight cases (29.6%) were grade 1, 5 (18.5%) were grade 2 and 14 (51.9%) were grade 3. The onset was in the first course in 17 (63.0%), 2nd course in 5 (18.5%), 3rd course in 2 (7.4%), 4th course in 1 (3.7%) and 5th course in 2 (7.4%). No treatment was administered in 1 case (3.7%), topical steroid was applied in 10 (37.0%), antiallergic drug was administered in 2 (7.4%), topical steroid and antiallergic drug were administered in 5 (18.5%), and oral and topical steroid and antiallergic drug were administered in 9 (33.3%). The 3-year progression-free survival (PFS) and overall survival (OS) in patients with rash development were 80.0% and 85.5%, respectively, and those in patients without development were 36.4% and 54.0%, respectively (p=0.009 and 0.02, respectively). By multivariate analysis, the development of rash was associated with a better PFS and a diagnosis of iBCL was associated with a better OS. This study revealed that bendamustine-induced rash is associated with a favorable prognosis among patients with iBCL.


Assuntos
Exantema , Linfoma de Células B , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/efeitos adversos , Exantema/induzido quimicamente , Exantema/tratamento farmacológico , Feminino , Humanos , Linfoma de Células B/patologia , Prognóstico , Estudos Retrospectivos , Rituximab
14.
Rinsho Ketsueki ; 62(8): 1038-1049, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497190

RESUMO

Myelodysplastic syndrome (MDS) is a group of clonal diseases caused by the accumulation of genetic mutations. The outcome of MDS extremely varies, with an overall survival ranging from just a few months to years. Therefore, accurate classification and prognostic scoring are essential. Patients with MDS are generally divided into two risk groups. For low-risk patients, the treatment goal is to improve ineffective hematopoiesis and quality of life. Meanwhile, in high-risk patients, treatment aims to extend survival and prevent progression to leukemia. To date, different guidelines recommend azacytidine, which is a hypomethylating agent, as the initial treatment. This is the only therapy associated with a significant survival in high-risk patients who are not eligible for hematopoietic stem cell transplantation. However, the response rate is only about 40%, and responses are mostly transient. Recent advancements in sequencing technologies have improved our understanding of the molecular pathogenesis of MDS by identifying somatic mutations in almost each patient with MDS. The high phenotypic and clinical heterogeneity of patients with MDS is primarily based on genetics. Due to a high degree of heterogeneity, the treatment policy for patients with MDS is still challenging. In this review, we will discuss the current treatment strategies for MDS in Japan, including future perspectives.


Assuntos
Síndromes Mielodisplásicas , Qualidade de Vida , Azacitidina , Genômica , Humanos , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/terapia , Fatores de Risco
15.
Leuk Res Rep ; 15: 100231, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33354513

RESUMO

To determine the impact of peripheral blood (PB) Wilms' tumour 1 (WT-1) mRNA levels in patients with primary myelodysplastic syndromes (MDS), we analysed the relationships between several clinical variables at the time of diagnosis and the haematological response of patients treated with azacytidine. We observed overall responses in 20 (63%) patients; there were no significant differences in clinical variables, including bone marrow blast counts, IPSS scores and IPSS-R risk scores, between responders and non-responders. The responders' PB WT-1 mRNA levels were significantly lower than those of non-responders (P = 0.03). PB WT-1 mRNA expression could be a marker for predicting the response to azacytidine in patients with de novo MDS.

16.
Rinsho Ketsueki ; 61(8): 874-878, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32908049

RESUMO

A 74-year-old man was admitted to hospital due to suspected acute leukemia. He had a history of thymic carcinoma, which had been treated with carboplatin in combination with either paclitaxel or amrubicin. However, the tumor remained unresponsive to these treatments. Administration of tegafur/gimeracil/oteracil (TS-1) was initiated, which resulted in tumor size reduction and a partial response. However, leukopenia persisted after the last TS-1 treatment, and four years after the initial treatment, increased blast cell counts were found in a blood film . Bone marrow analysis showed blasts with Auer rods, faggot cells, and dysplastic promyelocytes. Flow cytometry was positive for CD13, CD33, CD34, CD117, and myeloperoxidase, but negative for HLA-DR. PML-RARA fluorescence in situ hybridization was positive. Cytogenetic analysis revealed 47,XY,t (15;17) (q22;q21),+21. Thus, therapy-related acute promyelocytic leukemia (tAPL) was diagnosed. The patient achieved and maintained complete remission for more than 20 months by a de novo APL-treatment regimen including all-trans retinoic acid, arsenic trioxide and tamibarotene. Moreover, the thymic carcinoma has remained stable. Although secondary malignancies of thymic carcinoma have been previously reported, therapy-related leukemia, especially tAPL, is very rare.


Assuntos
Leucemia Promielocítica Aguda , Timoma , Neoplasias do Timo , Idoso , Humanos , Hibridização in Situ Fluorescente , Masculino , Translocação Genética
17.
Sci Rep ; 10(1): 14734, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895431

RESUMO

In this study, we developed the world's first artificial intelligence (AI) system that assesses the dysplasia of blood cells on bone marrow smears and presents the result of AI prediction for one of the most representative dysplasia-decreased granules (DG). We photographed field images from the bone marrow smears from patients with myelodysplastic syndrome (MDS) or non-MDS diseases and cropped each cell using an originally developed cell detector. Two morphologists labelled each cell. The degree of dysplasia was evaluated on a four-point scale: 0-3 (e.g., neutrophil with severely decreased granules were labelled DG3). We then constructed the classifier from the dataset of labelled images. The detector and classifier were based on a deep neural network pre-trained with natural images. We obtained 1797 labelled images, and the morphologists determined 134 DGs (DG1: 46, DG2: 77, DG3: 11). Subsequently, we performed a five-fold cross-validation to evaluate the performance of the classifier. For DG1-3 labelled by morphologists, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 91.0%, 97.7%, 76.3%, 99.3%, and 97.2%, respectively. When DG1 was excluded in the process, the sensitivity, specificity, PPV, NPV, and accuracy were 85.2%, 98.9%, 80.6%, and 99.2% and 98.2%, respectively.


Assuntos
Medula Óssea/patologia , Síndromes Mielodisplásicas/patologia , Algoritmos , Inteligência Artificial , Aprendizado Profundo , Humanos , Redes Neurais de Computação , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade
18.
Cancer Sci ; 111(7): 2472-2481, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32391628

RESUMO

In this phase II multicenter study (JALSG AML209-FLT3-SCT), we aimed to prospectively elucidate the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) for FLT3-internal tandem duplication (ITD)-positive AML. Newly diagnosed de novo AML patients with FLT3-ITD were enrolled at the achievement of CR1 and received allo-HSCT as soon as possible after the first consolidation therapy. Mutations of 57 genes in AML cells at diagnosis were also analyzed. Among 48 eligible patients with a median age of 38.5 (17-49) years, 36 (75%) received allo-HSCT at a median of 108 days after CR1. The median follow-up was 1726 days. The primary end-point, 3-year disease-free survival (DFS) based on an intent to treat analysis, was 43.8% (95% confidence interval [CI], 30%-57%), suggesting the efficacy of this treatment because the lower limit of the 95% CI exceeded the threshold response rate of 20%. The 3-year overall survival, post-transplant DFS, and non-relapse mortality rates were 54.2% (95% CI, 39%-67%), 58.3% (95% CI, 41%-72%), and 25.0% (95% CI, 12%-40%), respectively. The median ITD allelic ratio (AR) was 0.344 (0.006-4.099). Neither FLT3-ITD AR nor cooccurring genetic alterations was associated with a poor DFS. This prospective study indicated the efficacy and safety of allo-HSCT for FLT3-ITD AML patients in CR1. This study was registered at: www.umin.ac.jp/ctr/ as #UMIN000003433.


Assuntos
Expansão das Repetições de DNA , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
19.
J Clin Exp Hematop ; 60(1): 7-10, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32224564

RESUMO

Successful treatment of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract (ITLPDGI) by chemotherapy is rare and watchful waiting is often performed for asymptomatic patients. We report a case of ITLPDGI successfully treated by involved field radiotherapy (IFRT). The patient presented with slow ITLPDGI localised to the stomach with mild symptoms. IFRT (30 Gy/20f) was administered, after which endoscopy revealed resolution of lesions and blood vessel appearance, and absence of proliferating abnormal lymphocytes was confirmed by biopsy. The patient remains lymphoma-free 1 year post-treatment. Although long-term follow-up and additional cases are essential for the evaluation of IFRT as a treatment option for localised ITLPDGL, complete remission after relatively low-dose IFRT is promising, particularly as this has been rarely achieved by chemotherapy.


Assuntos
Transtornos Linfoproliferativos/radioterapia , Neoplasias Gástricas/radioterapia , Idoso , Feminino , Humanos , Transtornos Linfoproliferativos/patologia , Estômago/patologia , Estômago/efeitos da radiação , Neoplasias Gástricas/patologia , Linfócitos T/patologia , Linfócitos T/efeitos da radiação , Resultado do Tratamento
20.
Leuk Res ; 91: 106336, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32151888

RESUMO

The 2017 WHO classification includes a new provisional entity of indolent T-lymphoproliferative disorders of the gastrointestinal tract (ITLPD-GIT). We investigated GI involvement of peripheral T-cell lymphoma (PTCL). Eighty-two patients were diagnosed with PTCL during 2007-2017. Eleven patients (13 %) had histologically-confirmed GI tract involvement {3 monomorphic epitheliotropic intestinal lymphoma (MEITL), 3 extranodal NK-/T-cell lymphoma nasal type (ENKL), 2 PTCL, not otherwise specified, 1 adult T-cell leukemia-lymphoma, 2 ITLPD-GIT}. Three patients each had lesions in the small intestine and multiple lesions, two each in the stomach and colon, and one in the duodenum. Six of the 11 patients remained alive. No perforation/stenosis was observed after chemo-radiotherapy, although one patient with ENKL developed gastric bleeding during chemotherapy. One patient with ITLPD-GIT (CD4-/CD8+/Ki67Low) with a colonic lesion showing diffuse edema and multiple aphtha by endoscope and diarrhea, initially diagnosed with MEITL, had active but stable disease after various chemotherapies for 1 year and no therapy for the next 5 years. Another patient with ITLPD-GIT (CD4+/CD8+/Ki67Low) with a localized gastric lesion and slight epigastralgia was in remission for 1 year after radiation. In conclusion, about 10 % of PTCLs were complicated by GI tract lesions and most had a poor prognosis. ITLPD-GIT should be considered as a differential diagnosis based on histology and clinical course. Local complications after chemo/radiotherapy in PTCL with GI involvement were not frequent.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Raios gama/uso terapêutico , Gastroenteropatias/terapia , Linfoma Extranodal de Células T-NK/terapia , Linfoma de Células T Periférico/terapia , Adulto , Idoso , Bleomicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Diagnóstico Diferencial , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/mortalidade , Gastroenteropatias/patologia , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/patologia , Trato Gastrointestinal/efeitos da radiação , Humanos , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/patologia , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/patologia , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Prednisona/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêutico
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