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1.
Eur J Neurosci ; 59(1): 119-131, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37969020

RESUMO

Post-chemotherapy cognitive impairment, also known as 'chemobrain', is a common neurotoxic complication induced by chemotherapy, which has been reported in many cancer survivors who have undergone chemotherapy. In this study, we aimed to explore the effects of D-neneneba dicitabine, C-nenenebb cytarabine, A-aclamycin, G-granulocyte colony-stimulating factor (D-CAG) chemotherapy on cognitive function in patients with acute myeloid leukaemia (AML) and its possible central mechanisms. Twenty patients with AML and 25 matched healthy controls (HC) were enrolled in this study. The cognitive function of patients before and after D-CAG chemotherapy was evaluated by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog). The resting-state functional magnetic resonance imaging data were collected from all patients before and after chemotherapy intervention, as well as HC. Then, resting-state functional magnetic resonance imaging data were preprocessed using DPABI software package and regional homogeneity (ReHo) values of brain regions were calculated. Finally, ReHo values between groups were compared by Resting-State fMRI Data Analysis software package with t-tests and Alphasim method was performed for multiple comparison correction. Moreover, associations between ReHo values of altered brain regions and the scores of FACT-Cog were analysed by Pearson correlation. The total FACT-Cog scores and four factor scores of AML patients increased significantly after treatment. ReHo values showed no significant changes in patients before treatment when compared with HC. Compared with HC, ReHo values of the right middle frontal gyrus, inferior frontal gyrus (opercular part), middle occipital gyrus, and left praecuneus decreased significantly, while ReHo values of the left inferior temporal gyrus, right middle temporal gyrus, and hippocampus increased significantly in patients after treatment. Compared with patients before treatment, ReHo values decreased significantly in the right middle frontal gyrus, inferior frontal gyrus (opercular part), and middle and inferior occipital gyri of patients after treatment. In addition, ReHo values of the right inferior frontal gyrus (opercular part) were negatively correlated with the total scores of FACT-Cog and factor scores of perceived cognitive impairment in patients after treatment. There were also negative correlations between ReHo values of the right middle frontal gyrus and perceived cognitive impairment scores. The present study confirmed that D-CAG chemotherapy might cause impaired subjective self-reported cognitive functioning in AML patients, which might be related to the decreased function of certain regions in the right prefrontal lobe. These findings provided further understanding of the mechanisms involved in post-chemotherapy cognitive impairment and would help develop new therapeutic strategies for 'chemobrain' in AML patients.


Assuntos
Mapeamento Encefálico , Leucemia Mieloide Aguda , Humanos , Encéfalo/diagnóstico por imagem , Cognição , Imageamento por Ressonância Magnética/métodos , Leucemia Mieloide Aguda/diagnóstico por imagem , Leucemia Mieloide Aguda/tratamento farmacológico
2.
BMC Cancer ; 24(1): 458, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609917

RESUMO

BACKGROUND: The identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML). METHODS: 952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements. RESULTS: Three CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P < 0.01). A CT-MSF nomogram showed a performance with AUCs of 0.717, 0.794, 0.796 and 0.792 for predicting the 1-, 2-, 3-, and 5-year overall survival (OS) probabilities in the validation cohort, which were significantly higher than the ELN risk model. Moreover, a new MSN stratification system (MSF nomogram plus ELN risk model) could stratify patients into new high, intermediate and low risk group. Patients with high MSN risk may benefit from intensive treatment (P = 0.0011). CONCLUSIONS: In summary, the chest CT-MSF nomogram, integrating myosarcopenia, spleen_CTV, and SF_CTV features, could be used to predict prognosis of AML.


Assuntos
Leucemia Mieloide Aguda , Nomogramas , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Área Sob a Curva , Leucemia Mieloide Aguda/diagnóstico por imagem
3.
J Magn Reson Imaging ; 58(5): 1353-1363, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37154163

RESUMO

BACKGROUND: The bone marrow (BM) evaluation of acute leukemia (AL) mainly depends on invasive BM puncture biopsy. Noninvasive and accurate MR examination technology has potential clinical application value in the BM evaluation of AL patients. Multi-gradient-echo (MGRE) has been found useful to evaluate changes in BM fat and iron content, but has not yet been applied in AL. PURPOSE: To explore the diagnostic capability of BM infiltration of quantitative BM fat fraction (FF) and R2* values obtained from a 3D MGRE sequence in children with primary AL. STUDY TYPE: Prospective. POPULATION/SUBJECTS: Sixty-two pediatric patients with untreated AL and 68 healthy volunteers. AL patients were divided into acute lymphoblastic leukemia (ALL) (n = 39) and acute myeloid leukemia (AML) (n = 23) groups. FIELD STRENGTH/SEQUENCE: 3T, 3D chemical-shift-encoded multi-gradient-echo, T1WI, T2WI, T2_STIR. ASSESSMENT: BM FF and R2* values were assessed by manually drawing regions of interest at the L3, L4, ilium, and 1 cm below the bilateral trochanter of the femur (upper femur). STATISTICAL TESTS: Independent sample t-tests, variance analysis, Spearman correlation. RESULTS: BM FF and R2* at L3, L4, ilium, and upper femur, FFtotal and R2*total were significantly lower in the AL than control group. BM FF did not significantly differ between ALL and AML groups (PL3 = 0.060, PL4 = 0.086, Pilium = 0.179, Pupper femur = 0.149, and Ptotle = 0.097, respectively). The R2* was significantly lower in ALL group than AML group for L3, L4, and R2*total . BM FF was moderately positively correlated with R2* in ALL group, and strongly positively correlated in AML group. Area under the receiver operating characteristic curves showed that BM FF had higher AUC in AL, ALL, and AML (all AUC = 1.000) than R2* (0.976, 0.996, and 0.941, respectively). DATA CONCLUSION: MGRE-MRI mapping can be applied to measure BM FF and R2* values, and help evaluate BM infiltration and iron storage in children with AL. EVIDENCE LEVEL: 1 Technical Efficacy: 2.


Assuntos
Medula Óssea , Leucemia Mieloide Aguda , Humanos , Criança , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Estudos Prospectivos , Imageamento por Ressonância Magnética , Leucemia Mieloide Aguda/diagnóstico por imagem , Ferro/análise
4.
Ann Hematol ; 102(5): 1045-1052, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36947211

RESUMO

Cranial imaging (CI) is a widely used diagnostic procedure, especially in acute myeloid leukemia (AML) patients with suspected bleeding or infection. However, common clinical decision rules to guide CI do not apply to AML patients and the diagnostic yield and outcomes of CI for AML patients are largely unknown. We retrospectively evaluated all CI from newly diagnosed non-promyelocytic AML patients receiving intensive induction or consolidation chemotherapy between 2007 and 2019 for imaging indications, diagnostic yield, and consequences. A total of 110 of 462 patients (24%) received CI for 152 imagings in distinct clinical situations. Forty-four patients (40%) had at least one new and acute pathological finding. Main indication was focal neurologic deficit, craniocerebral trauma, and suspected cerebral hypertension. The most common new finding was intracranial hemorrhage (13% of all imagings), followed by sinusitis (9%). CI led to therapy change in 21 patients. There were no clear associations between indications, laboratory values, and a positive imaging. Positive imaging was associated with adverse overall survival. Our study suggests that the overall rate of ordered CI was appropriate and that CI should generally be performed at a low threshold. A systematized approach to CI may further increase diagnostic yield but is complicated by variable clinical presentation.


Assuntos
Leucemia Mieloide Aguda , Humanos , Estudos Retrospectivos , Leucemia Mieloide Aguda/diagnóstico por imagem , Leucemia Mieloide Aguda/tratamento farmacológico , Quimioterapia de Indução , Quimioterapia de Consolidação , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
5.
Childs Nerv Syst ; 39(12): 3607-3612, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37300577

RESUMO

INTRODUCTION: Intracranial myeloid sarcoma is a rare extramedullary presentation of acute myeloid leukemia (AML). It can involve the meninges and ependyma presenting as extra-axial mass lesion. Rarely, it can also invade the brain parenchyma. It is commonly seen in children. It is usually misdiagnosed due to its close resemblance to other intracranial tumors (meningioma, metastasis, Ewing's sarcomas, and lymphoma). These are underdiagnosed if they precede the diagnosis of leukemia. CASE REPORT: A 7-year-old boy with isolated intracranial myeloid sarcoma who presented with raised intracranial pressure (ICP) which was successfully managed by surgical excision. CONCLUSION: Isolated intracranial myeloid sarcoma is a rare presentation of AML. Leukemia can be diagnosed early during the postoperative period and can be started on therapy timely. These patients requires regular follow-ups (clinical, laboratory and radiological) to detect relapses early.


Assuntos
Neoplasias Encefálicas , Leucemia Mieloide Aguda , Neoplasias Meníngeas , Sarcoma de Ewing , Sarcoma Mieloide , Masculino , Criança , Humanos , Sarcoma Mieloide/diagnóstico por imagem , Sarcoma Mieloide/cirurgia , Leucemia Mieloide Aguda/diagnóstico por imagem , Leucemia Mieloide Aguda/patologia , Neoplasias Meníngeas/diagnóstico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia
6.
Acta Radiol ; 64(4): 1573-1578, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36317293

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Bone marrow computed tomography (CT) attenuation may increase in patients with myeloproliferative disorders; however, the actual threshold CT attenuation value predictive of myeloproliferative has not been reported. PURPOSE: To determine whether the unenhanced CT attenuation value of the bone marrow may be useful for predicting AML. MATERIAL AND METHODS: We retrospectively analyzed patients with AML (n = 56) who underwent unenhanced CT before treatment, and age- and sex-matched controls without any hematologic disease. For each patient, the CT attenuation value (HU) of the iliac bone was measured and compared between the two groups. Receiver operating characteristic (ROC) curve analysis was used to define the cutoff value for predicting AML on all patients, and only on late elderly patients (aged ≥75 years). RESULTS: Patients with AML showed higher bone marrow CT attenuation value (131.4 ± 58.3 vs. 53.9 ± 67.2 HU; P < 0.001), compared to the controls. The sensitivity and specificity for the diagnosis of AML in all patients were 78.6% and 80.4%, respectively, at a threshold value of 90 HU, whereas they were 83.3% and 91.7%, respectively, at 40 HU in late elderly patients. CONCLUSION: The iliac bone CT attenuation value was elevated in patients with AML and may be useful for predicting AML.


Assuntos
Medula Óssea , Leucemia Mieloide Aguda , Adulto , Idoso , Humanos , Medula Óssea/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Sensibilidade e Especificidade , Leucemia Mieloide Aguda/diagnóstico por imagem
7.
Haematologica ; 105(6): 1552-1558, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31467130

RESUMO

Extramedullary (EM) disease in patients with acute myeloid leukemia (AML) is a known phenomenon. Since the prevalence of EM AML has so far only been clinically determined on examination, we performed a prospective study in patients with AML. The aim of the study was to determine the prevalence of metabolically active EM AML using total body 18Fluorodesoxy-glucose positron emission tomography/computed tomography (18FDG-PET/CT) imaging at diagnosis prior to initiation of therapy. In order to define the dynamics of EM AML throughout treatment, PET-positive patients underwent a second 18FDG-PET/CT imaging series during follow up by the time of remission assessment. A total of 93 patients with AML underwent 18FDG-PET/CT scans at diagnosis. The prevalence of PET-positive EM AML was 19% with a total of 65 EM AML manifestations and a median number of two EM manifestations per patient (range, 1-12), with a median maximum standardized uptake value of 6.1 (range, 2-51.4). When adding those three patients with histologically confirmed EM AML who were 18FDG-PET/CT negative in the 18FDG-PET/CT at diagnosis, the combined prevalence for EM AML was 22%, resulting in 77% sensitivity and 97% specificity. Importantly, 60% (6 of 10) patients with histologically confirmed EM AML still had active EM disease in their follow up 18FDG-PET/CT. 18FDG-PET/CT reveals a high prevalence of metabolically active EM disease in AML patients. Metabolic activity in EM AML may persist even beyond the time point of hematologic remission, a finding that merits further prospective investigation to explore its prognostic relevance. (Trial registered at clinicaltrials.gov identifier: 01278069).


Assuntos
Fluordesoxiglucose F18 , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/diagnóstico por imagem , Leucemia Mieloide Aguda/epidemiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Prevalência , Estudos Prospectivos , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade
8.
J Magn Reson Imaging ; 51(6): 1720-1726, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31737979

RESUMO

BACKGROUND: An accurate and noninvasive method is of great importance to assess angiogenesis and cellularity of bone marrow in acute leukemia (AL). PURPOSE: To investigate whether the intravoxel incoherent motion (IVIM) parameters correlate with the histological characteristics of infiltrated marrow in AL patients and compare the difference between acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). STUDY TYPE: Prospective. POPULATION MODEL: Forty newly diagnosed patients with AL, including 20 AML and 20 ALL. FIELD STRENGTH/SEQUENCE: 1.5T/T1 WI and IVIM. ASSESSMENT: IVIM-derived parameters (true diffusion coefficient D, pseudodiffusion coefficient D*, and perfusion fraction, f) were measured in lumbar marrow. Histopathological analyses were performed from samples of marrow biopsy. STATISTICAL TESTS: The correlations between IVIM parameters and histological parameters used the Spearman correlation test. The difference of IVIM parameters and histological parameters between ALL and AML groups used the unpaired t-test or Mann-Whitney U-test, as appropriate. RESULTS: The f was positively correlated with microvessel density (MVD) in patients with ALL, AML, and AL (r = 0.740, P = 0.006; r = 0.771, P < 0.001; and r = 0.750, P < 0.001, respectively). There were no significant correlations between D and bone marrow cellularity in the three groups (r = -0.289, P = 0.362; r = 0.281, P = 0.292; and r = 0.058, P = 0.769, respectively). D and f values of ALL were higher than that of AML group (t = 3.332, P = 0.003 and t = 2.600, P = 0.014, respectively). MVD was higher in ALL than AML (t = 2.120, P = 0.044), whereas bone marrow cellularity had no significant difference between AML and ALL (t = -0.682, P = 0.501). DATA CONCLUSION: The f value derived from IVIM in bone marrow was positively correlated with MVD, while f might be able to show a difference of vascularity between ALL and AML. Therefore, the f value can be used as an alternative imaging marker of angiogenesis in marrow of AL patients. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1720-1726.


Assuntos
Medula Óssea , Leucemia Mieloide Aguda , Medula Óssea/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Humanos , Leucemia Mieloide Aguda/diagnóstico por imagem , Movimento (Física) , Estudos Prospectivos
9.
Cancer ; 125(20): 3566-3573, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31225904

RESUMO

BACKGROUND: Autologous stem cell transplantation (ASCT) is a potential consolidation therapy for acute myeloid leukemia (AML). This study was designed to develop a prediction model for leukemia-free survival (LFS) in a cohort of patients with de novo AML treated with ASCT during their first complete remission. METHODS: This was a registry study of 956 patients reported to the European Society for Blood and Marrow Transplantation. The primary outcome was LFS. Multivariate Cox regression modeling with backward selection was used to select variables for the construction of the nomogram. The nomogram's performance was evaluated with discrimination (the area under the receiver operating characteristic curve [AUC]) and calibration. RESULTS: Age and cytogenetic risk (with or without FMS-like tyrosine kinase 3 internal tandem duplication) were predictive of LFS and were used for the construction of the nomogram. Each factor in the nomogram was ascribed points according to its predictive weight. Through the calculation of the total score, the probability of LFS at 1, 3, and 5 years for each patient could be estimated. The discrimination of the nomogram, measured as the AUC, was 0.632 (95% confidence interval [CI], 0.595-0.669), 0.670 (95% CI, 0.635-0.705), and 0.687 (95% CI, 0.650-0.724), respectively. Further validation with bootstrapping showed similar AUCs (0.629 [95% CI, 0.597-0.657], 0.667 [95% CI, 0.633-0.699], and 0.679 [95% CI, 0.647-0.712], respectively), and this suggested that the model was not overfitted. Calibration was excellent. Patients were stratified into 4 incremental 5-year prognostic groups, with the probabilities of LFS and overall survival ranging from 25% to 64% and from 33% to 79%, respectively. CONCLUSIONS: The Auto-AML nomogram score is a tool integrating individual prognostic factors to provide a probabilistic estimation of LFS after ASCT for patients with AML.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/terapia , Nomogramas , Transplante Autólogo/efeitos adversos , Adulto , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico por imagem , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Indução de Remissão
10.
Ann Hematol ; 98(2): 351-359, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30341537

RESUMO

Skeletal muscle atrophy and loss of adipose tissue, referred to as sarcopenia and adipopenia, respectively, are often observed in cancer patients. We investigated the impact of sarcopenia and adipopenia on clinical outcomes in 90 adult patients with newly diagnosed acute myeloid leukemia (AML) who received induction chemotherapy. Computed tomography (CT) before treatment revealed sarcopenia in 39 patients (43%) and adipopenia in 35 patients (39%). We analyzed the treatment efficacy of induction chemotherapy and survival outcomes. Three-year overall survival (OS) was 35% in the sarcopenic group and 67% in the non-sarcopenic group (P < 0.001). Three-year OS was 33% in the adipopenic group and 67% in the non-adipopenic group (P < 0.005). Multivariate analysis showed an association between sarcopenia and lower OS (hazard ratio, 2.27; 95% confidence interval, 1.11-4.79; P < 0.05), with other prognostic factors of performance status > 2 (P < 0.05) and adverse cytogenetic risk (P < 0.05). In elderly patients over 60 years old, 3-year OS was 0% for the sarcopenic group and 49% for the non-sarcopenic group (P < 0.0005). These results indicate the prognostic values of sarcopenia in adult patients with AML.


Assuntos
Leucemia Mieloide Aguda , Músculo Esquelético/diagnóstico por imagem , Sarcopenia , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico por imagem , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcopenia/diagnóstico por imagem , Sarcopenia/mortalidade , Taxa de Sobrevida
11.
Curr Treat Options Oncol ; 20(2): 15, 2019 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-30741367

RESUMO

OPINION STATEMENT: Acute myeloid leukemia (AML) patients with a complex karyotype (CK-AML) show at least 3 unrelated clonal cytogenetic abnormalities with notoriously poor outcome. Such cases fall into either AML with myelodysplasia-related changes or therapy-related AML in the current World Health Organization classification of AML. Allogeneic stem cell transplantation is one of the only treatment modalities that can provide a long-term survival benefit and is recommended as a consolidative treatment in patients who are able to achieve complete remission. Unfortunately, transplantation is also associated with a higher relapse rate and more than half of CK-AML patients relapse from disease within the first 2 years. The probability of achieving remission with traditional induction using cytarabine and daunorubicin or idarubicin ("7 + 3") is so small that investigational therapies should be considered up front in these patients. Less intensive therapeutic backbones, typically using one of the hypomethylating agents, azacitidine or decitabine, minimize toxicity and show a trend toward the improved overall survival. CPX 351 (Vyxeos) is a liposomal formulation of cytarabine and daunorubicin and this encapsulation leads to prolonged exposure to the two drugs. This drug is approved for AML patients with MDS-related changes and therapy-related AML, both of which are frequently associated with complex karyotype. Such patients show improved outcome in trials using this combination. Combination therapy that includes venetoclax (BCL2 inhibitor) with hypomethylating agents may also be appropriate for such patients.


Assuntos
Aberrações Cromossômicas , Leucemia Mieloide Aguda/diagnóstico por imagem , Leucemia Mieloide Aguda/terapia , Antineoplásicos/uso terapêutico , Quimioterapia de Consolidação , Transplante de Células-Tronco Hematopoéticas , Humanos , Cariótipo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Prognóstico , Indução de Remissão , Proteína Supressora de Tumor p53/genética
12.
J Oncol Pharm Pract ; 25(6): 1491-1496, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30041582

RESUMO

BACKGROUND: Acute respiratory failure is a leading cause of intensive care unit admission in patients with hematological malignancies; it carries a mortality rate exceeding 50%. Venovenous extracorporeal membrane oxygenation use in patients with acute hematologic malignancies concurrently receiving induction chemotherapy is not well studied. CASE PRESENTATION: A 44-year-old male developed acute respiratory distress syndrome in the setting of newly diagnosed acute myelogenous leukemia. He underwent successful induction chemotherapy while on venovenous extracorporeal membrane oxygenation. His course was complicated by a devastating subarachnoid hemorrhage. Life support modalities were discontinued in accordance to the wishes of the family. CONCLUSION: There is a lack of data to guide use of induction chemotherapy in patients with acute hematologic malignancies requiring venovenous extracorporeal membrane oxygenation, particularly with regard to dosing, safety, and efficacy of chemotherapeutic agents. This case highlights a potential role of venovenous extracorporeal membrane oxygenation in select young acute myelogenous leukemia patients who might benefit from this intervention and warrants further research.


Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Hemofiltração/métodos , Quimioterapia de Indução/métodos , Leucemia Mieloide Aguda/terapia , Síndrome do Desconforto Respiratório/terapia , Adulto , Evolução Fatal , Humanos , Unidades de Terapia Intensiva/tendências , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/diagnóstico por imagem , Masculino , Síndrome do Desconforto Respiratório/complicações , Síndrome do Desconforto Respiratório/diagnóstico por imagem
13.
Blood ; 127(11): 1449-58, 2016 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-26712908

RESUMO

Patients with relapsed acute myeloid leukemia (AML) have limited therapeutic options. Vesicular stomatitis virus (VSV)-interferon ß (IFNß)-sodium iodide symporter (NIS) is an oncolytic VSV encoding IFNß and the NIS reporter. Syngeneic AML C1498 tumors responded to IV therapy with VSV-murine IFNß (mIFNß)-NIS in a dose-dependent manner. Imaging for NIS expression showed robust virus infection within the tumors. Virus infection did not increase programmed death ligand 1 (PD-L1) on tumor cells. Combining VSV-mIFNß-NIS with anti-PD-L1 antibody (Ab) therapy enhanced antitumor activity compared with treatment with virus alone or Ab alone; this enhancement was not significant at higher VSV-mIFNß-NIS doses. Systemic VSV therapy reduced systemic C1498-green fluorescent protein (GFP) tumor burden in the blood, bone marrow, spleen, and liver of mice with AML. Combination VSV-mIFNß-NIS and anti-PD-L1 Ab therapy significantly enhanced the survival of these mice with no evidence of toxicity, compared with isotype control, anti-PD-L1, or virus alone. There was an increase in tumor-infiltrating CD4 and CD8 cells. Single-agent VSV-mIFNß-NIS virotherapy induced both VSV-specific and GFP-specific CD8 T cells as determined by IFN-γ enzyme-linked immunospot, pentamer, and intracellular IFN-γ staining assays. Both of these responses were further enhanced by addition of anti-PD-L1 Ab. Depletion of CD8 or natural killer cells, but not CD4 cells, resulted in loss of antitumor activity in the VSV/anti-PD-L1 group. Clinical samples from chronic myelomonocytic leukemia and acute myelomonocytic leukemia appear to be especially susceptible to VSV. Overall, our studies show that oncolytic virotherapy combined with immune checkpoint blockade is a promising approach to AML therapy.


Assuntos
Antígeno B7-H1/imunologia , Imunoterapia , Leucemia Mieloide Aguda/terapia , Terapia Viral Oncolítica , Vírus da Estomatite Vesicular Indiana/fisiologia , Animais , Antígeno B7-H1/análise , Medula Óssea/patologia , Linhagem Celular Tumoral , Terapia Combinada , Feminino , Genes Reporter , Vetores Genéticos/genética , Proteínas de Fluorescência Verde/genética , Humanos , Interferon beta/genética , Lentivirus/genética , Leucemia Mieloide Aguda/diagnóstico por imagem , Leucemia Mielomonocítica Aguda/patologia , Leucemia Mielomonocítica Crônica/patologia , Leucócitos Mononucleares/patologia , Subpopulações de Linfócitos/imunologia , Linfócitos do Interstício Tumoral/química , Linfócitos do Interstício Tumoral/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Neoplasias/análise , Cintilografia , Simportadores/genética , Carga Tumoral
14.
Tohoku J Exp Med ; 246(2): 141-146, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30369515

RESUMO

Myeloid sarcoma (MS) is an uncommon extramedullary malignant tumor, and often represents a subgroup of acute myeloid leukemia (AML). MS of paranasal sinus origin is extremely rare. We report an uncommon case of sinonasal MS associated with AML, who was successfully treated with hematopoietic stem-cell transplantation. A 39-year-old male was admitted with complaints of left nasal obstruction and proptosis. Computed tomography and magnetic resonance imaging identified a left ethmoidal mass involving the maxillary sinus, the orbit, and the skull base. Nasal endoscopic examination detected a whitish homogeneous mass occupying the left nasal cavity. Although accumulation of atypical lymphocytes was suspected based on initial pathological inspection, immunohistochemical analysis showed myeloperoxidase-positive myeloid cells. Together with concomitant leukocytosis (149,000/µL) composed of myeloid blast cells and excess of myeloblasts in the bone marrow, the patient was diagnosed as sinonasal MS with AML with maturation (French-American-British Classification M2). The patient was treated by chemotherapy (remission induction therapy with daunorubicin and cytarabine; salvage chemotherapy with high-dose cytarabine), radiotherapy (30 Gy in 10 fractions) and allogeneic hematopoietic stem-cell transplantation, and followed up for 12 months with no recurrence. Early diagnosis is critical for the best improvement of MS. MS of the paranasal sinuses may easily be misdiagnosed as malignant lymphoma or poorly differentiated carcinoma. Prompt hematological and immunohistological investigations with suspicion of MS are essential for correct diagnosis. Furthermore, we concisely review nine previously reported patients with MS and indicate the importance of hematopoietic stem-cell transplantation for good prognosis.


Assuntos
Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/patologia , Seios Paranasais/patologia , Sarcoma Mieloide/complicações , Sarcoma Mieloide/patologia , Adulto , Humanos , Leucemia Mieloide Aguda/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Seios Paranasais/diagnóstico por imagem , Sarcoma Mieloide/diagnóstico por imagem , Tomografia Computadorizada por Raios X
15.
Vet Radiol Ultrasound ; 59(5): 507-515, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29726055

RESUMO

Acute myeloid leukemia is an uncommon hematopoietic neoplasm of dogs that should be differentiated from lymphoid neoplasms, such as lymphoma, because of different treatment protocols and a worse prognosis. Thoracic radiography is performed frequently in dogs with suspected hematopoietic neoplasia, and detecting a mediastinal mass often prioritizes lymphoma as the most likely diagnosis. However, we have observed a mediastinal mass in several dogs with acute myeloid leukemia and hypothesized that (1) the frequency of a mediastinal mass was higher and (2) the size of the mass was larger in dogs with acute myeloid leukemia compared to dogs with lymphoid neoplasms. In this analytical study (observational, retrospective, and cross-sectional), the sample population included 238 dogs with hematopoietic neoplasia. These dogs were divided into lymphoid (large cell lymphoma, acute lymphoblastic leukemia) and myeloid groups based on standard phenotyping tests. A mediastinal mass was detected during thoracic radiography in 73/218 (33%) and nine of 20 (45%) dogs in the lymphoid and myeloid groups (P = 0.21), respectively. The median size ratio of mediastinal mass to cardiac silhouette was 0.20 and 0.23 in the lymphoid and myeloid groups (P = 0.96), respectively. Additionally, we observed normal thoracic radiographs in 111/218 (51%) dogs in the lymphoid group and nine of 20 (45%) dogs in the myeloid group. In conclusion, acute myeloid leukemia should be considered when a mediastinal mass is detected during radiography in dogs with suspected hematopoietic neoplasia-but the presence or size of a mediastinal mass does not differentiate between myeloid and lymphoid neoplasms.


Assuntos
Doenças do Cão/diagnóstico por imagem , Leucemia Mieloide Aguda/veterinária , Linfoma não Hodgkin/veterinária , Leucemia-Linfoma Linfoblástico de Células Precursoras/veterinária , Animais , Estudos Transversais , Doenças do Cão/etiologia , Cães , Feminino , Leucemia Mieloide Aguda/diagnóstico por imagem , Leucemia Mieloide Aguda/etiologia , Linfoma não Hodgkin/diagnóstico por imagem , Linfoma não Hodgkin/etiologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico por imagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Radiografia , Estudos Retrospectivos
16.
J Magn Reson Imaging ; 46(2): 476-482, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28211619

RESUMO

PURPOSE: To investigate the value of intravoxel incoherent motion (IVIM) parameters in evaluation of prognosis in patients with acute myeloid leukemia (AML) before treatment. MATERIALS AND METHODS: Fifty-three patients before standard chemotherapy underwent MRI scans at 1.5 Tesla using conventional diffusion weighted imaging (DWI) and IVIM (b = 0, 10, 25, 50, 100, 200, 400, 600, 800, 1000, 1200 s/mm2 ) in the sagittal plane covering the lumbar bone marrow. The IVIM parameters (perfusion fraction [f], molecular diffusion coefficient [D], and perfusion-related D [D*] and apparent diffusion coefficient (ADC) were extracted from the bone marrow images. All patients were divided into complete remission (CR) and nonremission (NR) group according to the treatment response. RESULTS: All patients underwent the first remission induction chemotherapy, with 33 patients achieved CR and 20 patients achieved NR. The ADC values were not significant different between the two groups (P = 0.118). However, D value of CR group was significantly higher (P = 0.010), and f value of CR group was significantly lower (P = 0.021) than those of NR group. D* values had no significant differences between the two groups (P = 0.955). The D and f values were significant prognostic factors of AML after controlling for potential confounding factors (age, gender and smoking). Using receiver operator characteristic analysis, the area under the curve of D and f were 0.759 and 0.666, respectively, in evaluating prognosis of AML before treatment. CONCLUSION: There were significant differences in IVIM parameters between CR and NR patients of AML before treatment, and the D and f could play a potential role in prognosticating patients with AML. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:476-482.


Assuntos
Medula Óssea/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Leucemia Mieloide Aguda/diagnóstico por imagem , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Idoso , Antineoplásicos/farmacologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Quimioterapia de Indução , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Projetos Piloto , Prognóstico , Curva ROC , Indução de Remissão , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Razão Sinal-Ruído , Fumar , Adulto Jovem
17.
Eur J Haematol ; 99(3): 286-288, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28543682

RESUMO

We report on a multidisciplinary management of a 68-year-old AML patient presenting with a PET-positive mediastinal tumour typical for lymph node metastasis. It was removed via minimally invasive thoracoscopic intervention and was identified as a thymus residual infiltrated by AML. Follow-up PET-CT scan after resection and remission induction chemotherapy was completely normal. To our knowledge, this is the first documented case report of AML presenting with PET-positive infiltrates of thymic and lymph node tissue along the aortic bow mimicking a second intrathoracic malignancy. Our observation indicates the usefulness of this imaging technique and supports clarification of these unusual findings in AML patients, in case of need also by invasive diagnostic procedures, to enable an adequate therapeutic decision.


Assuntos
Fluordesoxiglucose F18 , Leucemia Mieloide Aguda/diagnóstico por imagem , Leucemia Mieloide Aguda/patologia , Linfonodos/patologia , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Timo/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diagnóstico Diferencial , Transplante de Células-Tronco Hematopoéticas , Humanos , Biópsia Guiada por Imagem , Leucemia Mieloide Aguda/terapia , Masculino , Transplante Homólogo , Resultado do Tratamento
18.
Pediatr Blood Cancer ; 64(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28233411

RESUMO

Central nervous system (CNS) involvement in childhood acute myeloid leukemia (AML) can manifest as leukemic cells in the cerebrospinal fluid, a solid CNS tumor, or as neurological symptoms. We evaluated the presenting symptoms and neuroimaging findings in 33 of 34 children with AML and CNS involvement at diagnosis in the period 2000-2012 in Sweden, Finland, and Denmark. Imaging was performed in 22 patients, of whom 16 had CNS-related symptoms. Seven patients, including all but two with facial palsy, had mastoid cell opacification, considered an incidental finding. The frequent involvement of the mastoid bone with facial palsy warrants evaluation in larger series.


Assuntos
Doenças do Sistema Nervoso Central/etiologia , Leucemia Mieloide Aguda/complicações , Adolescente , Doenças do Sistema Nervoso Central/diagnóstico , Criança , Paralisia Facial/diagnóstico , Paralisia Facial/etiologia , Feminino , Humanos , Lactente , Leucemia Mieloide Aguda/diagnóstico por imagem , Masculino , Processo Mastoide/diagnóstico por imagem
19.
J Clin Lab Anal ; 31(2)2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27427422

RESUMO

BACKGROUND: Automated peripheral blood (PB) image analyzers usually underestimate the total number of blast cells, mixing them up with reactive or normal lymphocytes. Therefore, they are not able to discriminate between myeloid or lymphoid blast cell lineages. The objective of the proposed work is to achieve automatic discrimination of reactive lymphoid cells (RLC), lymphoid and myeloid blast cells and to obtain their morphologic patterns through feature analysis. METHODS: In the training stage, a set of 696 blood cell images was selected in 32 patients (myeloid acute leukemia, lymphoid precursor neoplasms and viral or other infections). For classification, we used support vector machines, testing different combinations of feature categories and feature selection techniques. Further, a validation was implemented using the selected features over 220 images from 15 new patients (five corresponding to each category). RESULTS: Best discrimination accuracy in the training was obtained with feature selection from the whole feature set (90.1%). We selected 60 features, showing significant differences (P < 0.001) in the mean values of the different cell groups. Nucleus-cytoplasm ratio was the most important feature for the cell classification, and color-texture features from the cytoplasm were also important. In the validation stage, the overall classification accuracy and the true-positive rates for RLC, myeloid and lymphoid blast cells were 80%, 85%, 82% and 74%, respectively. CONCLUSION: The methodology appears to be able to recognize reactive lymphocytes well, especially between reactive lymphocytes and lymphoblasts.


Assuntos
Citometria por Imagem/instrumentação , Processamento de Imagem Assistida por Computador/instrumentação , Leucemia Mieloide Aguda/diagnóstico por imagem , Linfócitos/patologia , Células Mieloides/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico por imagem , Núcleo Celular/patologia , Citoplasma/patologia , Humanos , Citometria por Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Linfócitos/classificação , Células Mieloides/classificação , Máquina de Vetores de Suporte
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