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1.
Haematologica ; 109(1): 60-71, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37345475

RESUMO

Measurable residual disease (MRD) is a powerful predictor of outcome in acute myeloid leukemia. In the early phases of treatment, MRD refines initial disease risk stratification and is used for the allocation to allogeneic transplant. Despite its well-established role, a relatively high fraction of patients eventually relapses albeit achieving MRDneg status. The aim of this work was to assess specifically the influence of baseline features and treatment intensity on the predictive value of an MRDneg status, particularly focusing on MRD2, measured after two consecutive chemotherapy cycles. Among baseline features, younger MRD2neg patients (<55 years) had a significantly longer disease-free survival (median not reached) compared to their older counterparts (median 25.0 months, P=0.013, hazard ratio=2.08). Treatment intensity, specifically the delivery of a high dose of cytarabine in induction or first consolidation, apparently had a pejorative effect on the outcome of MRD2neg patients compared to standard dose (P=0.048, hazard ratio=1.80), a finding also confirmed by the analysis of data extracted from the literature. The combination of age and treatment intensity allowed us to identify categories of patients, among those who reached a MRD2neg status, characterized by significantly different disease-free survival rate. Our data showed that variables such as age and intensity of treatment administered can influence the predictive value of MRD in patients with acute myeloid leukemia. In addition to underscoring the need for further improvement of MRD analysis, these findings call for a reasoned application of MRD data, as currently available, to modulate consolidation therapy on adequately estimated relapse rates.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adulto , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/tratamento farmacológico , Recidiva , Transplante Homólogo , Intervalo Livre de Doença , Doença Crônica , Neoplasia Residual/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Prognóstico
2.
J Allergy Clin Immunol ; 151(2): 485-493.e11, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36309122

RESUMO

BACKGROUND: Systemic mastocytosis (SM) encompasses a heterogeneous group of clonal disorders characterized by abnormal expansion of mast cells (MCs). Beyond KIT and other genes recurrently mutated in myeloid neoplasms, several genetic variants have been described as predisposing to the development of the disease and influencing its clinical phenotype. Increased copy number variants of the TPSAB1 gene were identified as a cause of nonclonal elevated tryptasemia and defined as hereditary α-tryptasemia (HαT). Moreover, HαT is enriched in patients with SM, where it can affect the incidence of mediator-related symptoms. OBJECTIVE: In a multicenter data set of 444 patients with MC disorders, we aimed to investigate the clinical correlates of germline TPSAB1 copy number gains. METHODS: Droplet digital PCR was performed in all cases to ascertain the presence of HαT. Clinical history along with blood values and bone marrow examination were analyzed. RESULTS: We confirmed a higher incidence of HαT+ cases (n = 59, 13.3%) in patients diagnosed with mastocytosis with respect to the general population (approximately 5%). HαT+ patients were characterized by a lower MC-associated disease burden and higher levels of tryptase. Several disease variables were coherent with this pattern, from bone marrow MC infiltration to MC-related histopathologic traits, which also accounted for a significantly higher incidence of clonal MC activation syndrome in HαT+ (10.2%) compared to HαT- (3.4%, P = .029) patients. We also confirmed that HαT+ carriers had a significantly higher frequency of anaphylaxis, without relevant differences for other clinical manifestations. CONCLUSION: These findings on a large patient series support and extend previous data, and suggest that knowledge of HαT status may be useful for personalized management of patients with SM.


Assuntos
Mastocitose Sistêmica , Mastocitose , Humanos , Mastocitose Sistêmica/genética , Mastocitose Sistêmica/diagnóstico , Relevância Clínica , Mastocitose/diagnóstico , Mastócitos/patologia , Triptases/genética
3.
J Clin Immunol ; 42(7): 1379-1391, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35809212

RESUMO

BACKGROUND AND PURPOSE: Waning immunity and the surge of SARS-CoV-2 variants are responsible for breakthrough infections, i.e., infections in fully vaccinated individuals. Although the majority of vaccinated infected subjects report mild or no symptoms, some others require hospitalization. The clinical and immunological features of vaccinated hospitalized COVID-19 patients are currently unknown. METHODS: Twenty-nine unvaccinated and 36 vaccinated hospitalized COVID-19 patients were prospectively enrolled and clinical and laboratory data were gathered. Immunophenotyping of leukocytes' subsets, T and B cell SARS-CoV-2-specific responses were evaluated via flow cytometry. Anti-IFN-α autoantibodies were measured via ELISA. RESULTS: Despite vaccinated patients were older and with more comorbidities, unvaccinated subjects showed higher levels of pro-inflammatory markers, more severe disease, and increased mortality rate. Accordingly, they presented significant alterations in the circulating leukocyte composition, typical of severe COVID-19. Vaccinated patients displayed higher levels of anti-Spike IgGs and Spike-specific B cells. Of all participants, survivors showed higher levels of anti-Spike IgGs and Spike-specific CD4+ T cells than non-survivors. At hospital admission, 6 out of 65 patients (9.2%) displayed high serum concentrations of autoantibodies targeting IFN-α. Remarkably, 3 were unvaccinated and eventually died, while the other 3 were vaccinated and survived. CONCLUSION: Despite more severe pre-existing clinical conditions, vaccinated patients have good outcome. A rapid activation of anti-SARS-CoV-2-specific immunity is fundamental for the resolution of the infection. Therefore, prior immunization through vaccination provides a significant contribution to prevention of disease worsening and can even overcome the presence of high-risk factors (i.e., older age, comorbidities, anti-IFN-α autoantibodies).


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Hospitalização , Autoanticorpos
4.
Am J Hematol ; 97(7): 846-855, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35338671

RESUMO

Prognostic modeling in myelofibrosis (MF) has classically pursued the integration of informative clinical and hematological parameters to separate patients' categories with different outcomes. Modern stratification includes also genetic data from karyotype and mutations. However, some poorly standardized variables, as peripheral blood (PB) blast count by morphology, are still included. In this study, we used multiparameter flow cytometry (MFC) with the aim of improving performance of existing scores. We studied 363 MF patients with available MFC files for PB CD34+ cells count determination at diagnosis. We adapted Ogata score to MF context including 2 parameters: absolute CD34+ cells count (/µL) and granulocytes to lymphocytes SSC ratio. A score of 1 was attributed to above-threshold values of each parameter. Accordingly, patients were categorized as MFClow (score = 0, 62.0%), MFCint (score = 1, 29.5%), and MFChigh (score = 2, 8.5%). MFClow had significantly longer median OS (not reached) compared to MFCint (55 months) and MFChigh (19 months). We integrated MFC into established models as a substitute of morphological PB blasts count. Patients were reclassified according to MFC-enhanced scores, and concordance (C-) indexes were compared. As regards IPSS, C-indexes were 0.67 and 0.74 for standard and MFC-enhanced model, respectively (Z score - 3.82; p = 0.0001). MFC-enhanced MIPSS70+ model in PMF patients yielded a C-index of 0.78, outperforming its standard counterpart (C-index 0.73; Z score - 2.88, p = 0.004). Our data suggest that the incorporation of MFC-derived parameters, easily attainable from standard assay used for CD34+ cells determination, might help to refine the current prognostic stratification models in myelofibrosis.


Assuntos
Mielofibrose Primária , Antígenos CD34 , Citometria de Fluxo , Humanos , Mutação , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/genética , Prognóstico
5.
Immunology ; 161(4): 345-353, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32870529

RESUMO

SARS-CoV-2 is responsible for a new infectious disease (COVID-19) in which individuals can either remain asymptomatic or progress from mild to severe clinical conditions including acute respiratory distress syndrome and multiple organ failure. The immune mechanisms that potentially orchestrate the pathology in SARS-CoV-2 infection are complex and only partially understood. There is still paucity of data on the features of myeloid cells involved in this viral infection. For this reason, we investigated the different activation status profiles and the subset distribution of myeloid cells and their correlation with disease progression in 40 COVID-19 patients at different stages of disease. COVID-19 patients showed a decrease in the absolute number of plasmacytoid and myeloid dendritic cells, different subset distribution of monocytes and different activation patterns of both monocytes and neutrophils, coupled to a significant reduction of HLA-DR monocyte levels. We found that some of these alterations are typical of all COVID-19 patients, while some others vary at different stages of the disease and correlate with biochemical parameters of inflammation. Collectively, these data suggest that not only the lymphoid, but also the myeloid compartment, is severely affected by SARS-CoV-2 infection.


Assuntos
COVID-19/imunologia , Células Dendríticas/imunologia , Células Mieloides/imunologia , Adulto , Idoso , COVID-19/patologia , Células Dendríticas/patologia , Feminino , Citometria de Fluxo , Humanos , Unidades de Terapia Intensiva , Masculino , Células Mieloides/patologia
6.
Am J Hematol ; 95(11): 1304-1313, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32697337

RESUMO

Minimal residual disease (MRD) assessment in acute myeloid leukemia (AML) is increasingly used in risk stratification. However, several issues around this use are unresolved, including, among others, the most suitable time-point(s) for its application. Overall, late assessments appear more effective at distinguishing outcome but, in some studies, the early evaluations were already highly informative, anticipating the value of later ones. Our work integrated MRD with peripheral blast clearance (PBC), a treatment-related biomarker previously demonstrated to be a powerful predictor of response. From 2007 to 2014, we have studied 120 patients treated according to the NILG 02-06 trial and who achieved CR after induction. Patients in PBC-defined categories (separated by a 1.5-log threshold) showed significantly different probabilities of attaining MRD negativity, after either induction (MRD1) or consolidation (MRD2). Peripheral blast clearance combined with MRD1 largely anticipated MRD2-related information: when both biomarkers predicted chemosensitive disease (PBChigh /MRD1neg ), the rate of MRD2-negativity was 90%, and DFS and OS estimates were 68% and 76% at 3 years, respectively. When both markers were unfavorable (PBClow /MRD1pos ), rates of MRD2 negativity, DFS, and OS were 20%, 34%, and 24%, respectively, at 3 years. In fact, MRD2 added prognostic value only in cases with discordant PBC/MRD1 data. Our data support a reasoned timing for MRD-based therapeutic decisions, modulated on individual chemosensitivity, an approach we have implemented in a forthcoming prospective multi-center trial by Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA).


Assuntos
Biomarcadores Tumorais/sangue , Crise Blástica , Leucemia Mieloide Aguda , Adolescente , Adulto , Idoso , Crise Blástica/sangue , Crise Blástica/mortalidade , Crise Blástica/terapia , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Taxa de Sobrevida
7.
Am J Hematol ; 94(8): 845-852, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31056768

RESUMO

Systemic mastocytosis (SM) is characterized by extreme heterogeneity of manifestations and prognosis. Several disease-related biomarkers, including clinical, hematological and molecular variables, have been correlated with prognosis. Although relevant, the mutation profile closely reflects the WHO classification that has per se prognostic value. High-risk mutations (HRM) are largely confined to advanced forms, and thus fail in providing information regarding progression and outcome in the not-advanced variants. In this work, we studied hematopoietic cells by multi-parameter flow cytometry (MFC) in order to highlight dysplastic traits that might provide insights into outcome. A score previously validated for myelodysplastic syndromes, with high reproducibility in standard diagnostics, was used. The application of an MFC score to a cohort of 71 SM cases, concurrently genotyped for configuring a HRM category, resulted in the identification of two separate patients' categories (MFC+ and MFC-) characterized by significantly different clinical and laboratory features at presentation. The extent of dysplasia by MFC tended to parallel WHO-category and genotype-related stratification. MFC+ patients had shorter survival compared to MFC- ones, for whom the incidence of progression and/or death was virtually null. Of note, MFC score remained prognostically informative in unadvanced subsets. Furthermore, the integration of MFC and HRM was an independent predictor for outcome, also overcoming WHO-categories in multivariate analysis for EFS. Our results support the use of MFC analysis in the evaluation of patients with SM, alone and in combination with HRM, for refinement of prognosis assessment.


Assuntos
Citometria de Fluxo/métodos , Mastocitose Sistêmica/genética , Mutação , Síndromes Mielodisplásicas/genética , Proteínas Proto-Oncogênicas c-kit/genética , Estudos de Coortes , Genótipo , Humanos , Imunofenotipagem , Prognóstico , Análise de Sobrevida
8.
Haematologica ; 102(3): 529-540, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28250006

RESUMO

Mutations in CCAAT/enhancer binding protein α (CEBPA) occur in 5-10% of cases of acute myeloid leukemia. CEBPA-double-mutated cases usually bear biallelic N- and C-terminal mutations and are associated with a favorable clinical outcome. Identification of CEBPA mutants is challenging because of the variety of mutations, intrinsic characteristics of the gene and technical issues. Several screening methods (fragment-length analysis, gene expression array) have been proposed especially for large-scale clinical use; although efficient, they are limited by specific concerns. We investigated the phenotypic profile of blast and maturing bone marrow cell compartments at diagnosis in 251 cases of acute myeloid leukemia. In this cohort, 16 (6.4%) patients had two CEBPA mutations, whereas ten (4.0%) had a single mutation. First, we highlighted that the CEBPA-double-mutated subset displays recurrent phenotypic abnormalities in all cell compartments. By mutational analysis after cell sorting, we demonstrated that this common phenotypic signature depends on CEBPA-double-mutated multi-lineage involvement. From a multidimensional study of phenotypic data, we developed a classifier including ten core and widely available parameters. The selected markers on blasts (CD34, CD117, CD7, CD15, CD65), neutrophil (SSC, CD64), monocytic (CD14, CD64) and erythroid (CD117) compartments were able to cluster CEBPA-double-mutated cases. In a validation set of 259 AML cases from three independent centers, our classifier showed excellent performance with 100% specificity and 100% sensitivity. We have, therefore, established a reliable screening method, based upon multidimensional analysis of widely available phenotypic parameters. This method provides early results and is suitable for large-scale detection of CEBPA-double-mutated status, allowing gene sequencing to be focused in selected cases.


Assuntos
Proteína alfa Estimuladora de Ligação a CCAAT/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Mutação , Fenótipo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Medula Óssea/patologia , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Análise por Conglomerados , Análise Citogenética , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Imunofenotipagem , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
9.
Pract Lab Med ; 40: e00401, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38812906

RESUMO

Introduction: Recently, a flow cytometric (FC) based test has been developed for detection of circulating fetal cells to replace the less accurate and reproducible Kleihauer-Betke test.FC test is easier to perform, it can distinguish the origin of fetal cells, but it is expensive and available in highly specialized laboratories. We evaluated the introduction of high-performance liquid chromatography (HPLC) approach as initial screening to identify patients who need an additional FC test to better discriminate the nature of haemoglobin-F (HbF) positive cells. Methods: Blood samples from 130 pregnant women suspected to have fetomaternal haemorrhage were analysed with HPLC and FC methods. The cut-off for HbF HPLC concentration was calculated. Statistical analyses for the evaluation of HPLC as a screening method were performed. The positivity cut-off of HbF to be used as decision-making value to continue the investigation was calculated. Results: An excellent agreement (R2 > 0.90) was observed between the percentage of HbF obtained by HPLC and the percentage of fetal cells detected by FC. Results obtained from each assay were compared to define the HPLC threshold below which it is not necessary to continue the investigations, confirming the maternal nature of the HbF positive cells detected. Our study demonstrated that a cut-off of 1.0 % HbF obtained by HPLC was associated with the lowest rate of false negative results in our patient cohort. Conclusions: This study provides a new FMH investigation approach that possibly leads to a reduction in times and costs of the analysis.

10.
Transl Oncol ; 26: 101552, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36183675

RESUMO

The identification of mature T cell neoplasms by flow cytometry is often challenging, due to overlapping features with reactive T cells and limitations of currently available T cell clonality assays. The description of an antibody specific for one of two mutually exclusive T cell receptor (TCR) ß-chain constant regions (TRBC1) provides an opportunity to facilitate the detection of clonal TCRαß+ T cells based on TRBC-restriction. Here we prospectively analyzed 14 healthy controls and 63 patients with the flow cytometry protocol currently used for suspected T cell neoplasm implemented with immunostaining targeting TRBC1. Specimens were firstly classified in 3 groups based on clinical records data, laboratory findings and immunophenotypic features. T cell clonality was assessed by TCR Vß repertoire analysis and the new rapid TRBC1 assay. Results showed that TRBC1 unimodal expression was unequivocally associated with samples presenting with immunophenotypic aberrancies. Moreover, we demonstrated that the use of TRBC1 is useful in solving uncertain cases and confirmed the high sensitivity of the method in identifying small T cell clones of uncertain significance (T-CUS). Finally, we found a high degree of concordance (97%) comparing the currently available clonality assessment methods with the proposed new method. In conclusion, our results provided real-life evidence of the utility of TRBC1 introduction in the flow cytometric clonality evaluation for the routine diagnostic work-up of T cell neoplasms.

11.
Methods Mol Biol ; 2285: 99-109, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33928546

RESUMO

T-cell receptor (TCR)-Vß repertoire analysis is a sensitive method for detection of T-cell clonality. This type of analysis has been used for studying selective T-cell responses in autoimmune disease, alloreactivity in transplantation, and protective immunity against microbial and tumor antigens and in neoplastic T cells. Here, we describe the flow cytometric methods to perform this analysis.


Assuntos
Citometria de Fluxo , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Subpopulações de Linfócitos T/metabolismo , Animais , Humanos , Imunofenotipagem , Fenótipo , Projetos de Pesquisa , Subpopulações de Linfócitos T/imunologia , Fluxo de Trabalho
12.
J Clin Med ; 10(8)2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33919958

RESUMO

Relapsed/refractory (R/R) acute myeloid leukemia (AML) is a largely unmet medical need, owing to the lack of standardized, effective treatment approaches, resulting in an overall dismal outcome. The only curative option for R/R AML patients is allogeneic hematopoietic stem cell transplantation (HSCT) which is only applicable in a fraction of patients due to the scarce efficacy and high toxicity of salvage regimens. Recently, a number of targeted agents with relatively favorable toxicity profiles have been explored in clinical trials for R/R AML patients. The Bcl-2 inhibitor venetoclax, in combination with hypomethylating agents or low dose cytarabine, has produced impressive results for newly diagnosed AML, while its role in R/R disease is not well defined yet. We retrospectively analyzed the clinical outcomes of 47 R/R AML patients treated with venetoclax-based regimens between March 2018 and December 2020 at our institution. Overall, we report a composite complete response rate of 55% with an overall acceptable toxicity profile. Outcomes were particularly favorable for NPM1 mutated patients, unlike for FLT3-ITD positive patients irrespective of NPM1 status. For patients treated with intention to transplant, the procedure could be finally performed in 54%. These findings suggest a role for venetoclax-based regimens in R/R AML patients and support the design of prospective studies.

13.
Leukemia ; 35(4): 1121-1133, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32814839

RESUMO

Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus high-flow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19/virologia , Ensaios de Uso Compassivo , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 2/antagonistas & inibidores , Inibidores de Janus Quinases/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , COVID-19/diagnóstico , COVID-19/metabolismo , Terapia Combinada , Comorbidade , Feminino , Humanos , Inibidores de Janus Quinases/farmacologia , Masculino , Pessoa de Meia-Idade , Nitrilas , Estudos Prospectivos , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Pirimidinas , Índice de Gravidade de Doença , Resultado do Tratamento , Carga Viral
14.
J Clin Microbiol ; 48(4): 1297-304, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20181903

RESUMO

The strain diversity and the population structure of nosocomial Acinetobacter isolated from patients admitted to different hospitals in Florence, Italy, during a 3-year surveillance program, were investigated by amplified fragment length polymorphism (AFLP). The majority of isolates (84.5%) were identified as A. baumannii, confirming this species as the most common hospital Acinetobacter. Three very distinct A. baumannii clonal groups (A1, A2, and A3) were defined. The A1 isolates appeared to be genetically related to the well-characterized European EU II clone. A2 was responsible for three outbreaks which occurred in two intensive care units. Space/time population dynamic analysis showed that A1 and A2 were successful nosocomial clones. Most of the A. baumannnii isolates were imipenem resistant. The genetic determinants of carbapenem resistance were investigated by multiplex PCR, showing that resistance, independently of hospital origin, period of isolation, or clonal group, was associated with the presence of a bla (OXA-58-like) gene and with ISAba2 and ISAba3 elements flanking this gene. bla (OXA-58) appeared to be horizontally transferred. This study showed that the high discriminatory power of AFLP is useful for identification and typing of nosocomial Acinetobacter isolates. Moreover the use of AFLP in a real-time surveillance program allowed us the recognition of clinically relevant and widespread clones and their monitoring in hospital settings. The correlation between clone diffusion, imipenem resistance, and the presence of the bla(OXA-58-like) gene is discussed.


Assuntos
Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/microbiologia , Acinetobacter/classificação , Acinetobacter/genética , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Polimorfismo Genético , Acinetobacter/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Técnicas de Tipagem Bacteriana , Carbapenêmicos/farmacologia , Criança , Pré-Escolar , Análise por Conglomerados , Impressões Digitais de DNA , DNA Bacteriano/genética , Genótipo , Humanos , Recém-Nascido , Unidades de Terapia Intensiva , Itália/epidemiologia , Epidemiologia Molecular , Adulto Jovem , Resistência beta-Lactâmica , beta-Lactamases/genética
15.
Haematologica ; 95(5): 833-6, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20107153

RESUMO

We investigated the prognostic significance of early peripheral blast clearance as assessed by WT1 transcript reduction during the first days of standard induction therapy in 57 adult patients with acute myeloid leukemia (AML). Quantification of WT1 transcript by real-time quantitative PCR in peripheral blood on days 1 and 5 of treatment was performed. WT1 ratio was defined as the ratio of copy number measured on day 1 and on day 5. The median WT1 ratio was greater in patients attaining CR as compared to non-responders (11.68 vs. 2.14, respectively; P=0.0006). Furthermore, DFS and OS were significantly longer in patients displaying a WT1 ratio greater than 5.82 (i.e. the median value of whole cohort) than in patients with WT1 ratio of 5.82 or under (P=0.024 and P<0.001, respectively). These data suggest that early decrease of WT1 copy number in peripheral blood predicts for better outcome and should be considered in the management of AML patients.


Assuntos
Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/tratamento farmacológico , Transcrição Gênica/fisiologia , Proteínas WT1/antagonistas & inibidores , Proteínas WT1/genética , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Crise Blástica/tratamento farmacológico , Crise Blástica/genética , Crise Blástica/metabolismo , Citarabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Genes do Tumor de Wilms/efeitos dos fármacos , Genes do Tumor de Wilms/fisiologia , Humanos , Idarubicina/administração & dosagem , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Taxa de Sobrevida/tendências , Fatores de Tempo , Transcrição Gênica/efeitos dos fármacos , Resultado do Tratamento , Proteínas WT1/sangue , Adulto Jovem
16.
Cancers (Basel) ; 12(11)2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33143086

RESUMO

Acute myeloid leukemia (AML) "with myelodysplasia-related changes (MRC)" is considered a separate entity by the World Health Organization (WHO) classification of myeloid neoplasms. While anamnestic and cytogenetic criteria provide objective attribution to this subset, with clear unfavorable prognostic significance, the actual role of multi-lineage dysplasia (MLD) as assessed by morphology is debated. The aim of our work was to study MLD by a technique alternative to morphology, which is multiparameter flow cytometry (MFC), in a large series of 302 AML patients intensively treated at our Center. The correlation with morphology we observed in the unselected analysis reiterated the capability of the MFC-based approach at highlighting dysplasia. MLD data, estimated through an immune-phenotypic score (IPS), provided no insight into prognosis when considered overall nor within well-defined genetic categories. Of interest, IPS-related dysplasia conveyed significant prognostic information when we focused on genetically undefined patients, triple-negative for NPM1, FLT3 and CEBPA (TN-AML). In this context, the lack of dysplastic features (IPS_0) correlated with a significantly higher CR rate and longer survival compared to patients showing dysplasia in one or both (neutrophil and erythroid) cell lineages. The impact of IPS category maintained its validity after censoring at allogeneic HSCT and in a multivariate analysis including baseline and treatment-related covariates. In a subgroup featured by the lack of genetic determinants, our data could help address the relative unmet needs in terms of risk assessment and treatment strategy, and provide insight into prediction of response in the rapidly evolving therapeutic scenario of AML.

17.
Blood Adv ; 4(2): 301-311, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31978214

RESUMO

Although genetics is a relevant risk factor in acute myeloid leukemia (AML), it can be minimally informative and/or not readily available for the early identification of patients at risk for treatment failure. In a randomized trial comparing standard vs high-dose induction (ClinicalTrials.gov #NCT00495287), we studied early peripheral blast cell clearance (PBC) as a rapid predictive assay of chemotherapy response to determine whether it correlates with the achievement of complete remission (CR), as well as postremission outcome, according to induction intensity. Individual leukemia-associated immunophenotypes (LAIPs) identified pretherapy by flow cytometry were validated and quantified centrally after 3 days of treatment, expressing PBC on a logarithmic scale as the ratio of absolute LAIP+ cells on day 1 and day 4. Of 178 patients, 151 (84.8%) were evaluable. Patients in CR exhibited significantly higher median PBC (2.3 log) compared with chemoresistant patients (1.0 log; P < .0001). PBC < 1.0 predicted the worst outcome (CR, 28%). With 1.5 log established as the most accurate cutoff predicting CR, 87.5% of patients with PBC >1.5 (PBChigh, n = 96) and 43.6% of patients with PBC ≤1.5 (PBClow, n = 55) achieved CR after single-course induction (P < .0001). CR and PBChigh rates were increased in patients randomized to the high-dose induction arm (P = .04) and correlated strongly with genetic/cytogenetic risk. In multivariate analysis, PBC retained significant predictive power for CR, relapse risk, and survival. Thus, PBC analysis can provide a very early prediction of outcome, correlates with treatment intensity and disease subset, and may support studies of customized AML therapy.


Assuntos
Imunofenotipagem/métodos , Leucemia Mieloide Aguda/imunologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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