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TKIs long-term treatment in CML may lead to persistent adverse events (AEs) that can promote relevant morbidity and mortality. Consequently, TKIs dose reduction is often used to prevent AEs. However, data on its impact on successful treatment-free remission (TFR) are quite scarce. We conducted a retrospective study on the outcome of CML subjects who discontinued low-dose TKIs from 54 Italian hematology centers participating in the Campus CML network. Overall, 1.785 of 5.108 (35.0%) regularly followed CML patients were treated with low-dose TKIs, more frequently due to relevant comorbidities or AEs (1.288, 72.2%). TFR was attempted in 248 (13.9%) subjects, all but three while in deep molecular response (DMR). After a median follow-up of 24.9 months, 172 (69.4%) patients were still in TFR. TFR outcome was not influenced by gender, Sokal/ELTS risk scores, prior interferon, number and last type of TKI used prior to treatment cessation, DMR degree, reason for dose reduction or median TKIs duration. Conversely, TFR probability was significantly better in the absence of resistance to any prior TKI. In addition, patients with a longer DMR duration before TKI discontinuation (i.e., >6.8 years) and those with an e14a2 BCR::ABL1 transcript type showed a trend towards prolonged TFR. It should also be emphasized that only 30.6% of our cases suffered from molecular relapse, less than reported during full-dose TKI treatment. The use of low-dose TKIs does not appear to affect the likelihood of achieving a DMR and thus trying a treatment withdrawal, but might even promote the TFR rate.
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We evaluated the impact of genomic polymorphisms in folate-metabolizing, DNA synthesis and DNA repair enzymes on the clinical outcome of 108 patients with myelodysplastic syndromes (MDS) receiving best supportive care (BSC) or azacitidine. A statistically significant association between methylenetetrahydrofolate reductase (MTHFR) 677T/T, thymidylate synthase (TS) 5'-untranslated region (UTR) 3RG, TS 3'-UTR -6 bp/-6 bp, XRCC1 399G/G genotypes and short survival was found in patients receiving BSC by multivariate analysis (P<0.001; P=0.026; P=0.058; P=0.024). MTHFR 677T/T, TS 3'-UTR -6 bp/-6 bp and XRCC1 399G/G genotypes were associated with short survival in patients receiving azacitidine by multivariate analysis (P<0.001; P=0.004; P=0.002). We then performed an exploratory analysis to evaluate the effect of the simultaneous presence of multiple adverse variant genotypes. Interestingly, patients with ⩾1 adverse genetic variants had a short survival, independently from their International Prognostic Scoring System (IPSS) and therapy received. To our knowledge, this is the first study showing that polymorphisms in folate-metabolizing pathway, DNA synthesis and DNA repair genes could influence survival of MDS patients.
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Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Timidilato Sintase/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Cuidados Paliativos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
INTRODUCTION: The high-throughput era remarkably changed molecular laboratory practice. Actually, the increasing number of processed samples requires to reduce the risk of operator biases, by automating or simplifying as much as possible both the analytical and the pre-analytical phases. Minimal residual disease (MRD) studies in hematology often require a simultaneous processing of many bone marrow and peripheral blood samples from patients enrolled in prospective, multicenter, clinical trials, monitored at several planned time points. METHODS: In this study, we demonstrate that red blood cell lysis (RBL) pre-analytical procedure can replace the time-consuming Ficoll stratification as cell recovering step. Here, we show a MRD comparison study using both total white blood cells and mononuclear cells recovered by the 2 procedures from 46 follicular lymphoma (FL), 15 multiple myeloma (MM), and 11 mantle cell lymphoma (MCL) patients enrolled in prospective clinical trials. RESULTS: The experiments were performed in the 4 laboratories of the Fondazione Italiana Linfomi (FIL) MRD Network and showed superimposable results, in terms of good correlation (R = 0.87) of the MRD data obtained by recovering blood cells by the 2 approaches. CONCLUSION: Based on these results, the FIL MRD Network suggests to optimize the pre-analytical phases introducing RBL approach for cell recovery in the clinical trials including MRD analysis.
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Ficoll , Hemólise , Neoplasia Residual/diagnóstico , Ensaios Clínicos como Assunto , Diatrizoato , Humanos , Leucócitos , Leucócitos Mononucleares , MétodosRESUMO
PURPOSE: The main objective of this study is to gain a deeper understanding of how patients suffering from chronic myeloid leukemia (CML) cope with their illness. The study aims to reconstruct the subjective meaning-making process related to CML in order to gain insights into the impact the disease has on patients' emotions and everyday lives, as well as to explore the psychological impact of their being presented with the chance to suspend their therapy and recover from the disease. METHODS: Data were gathered from a qualitative study conducted in Italy on 158 Italian CML patients. Basing the study on the narrative inquiry approach, the patients were required to describe their patient journey in a qualitative narrative diary. These contained prompts to elicit the free expression of their needs, expectations, and priorities. A lexicographic analysis was carried out with T-LAB software and in particular a thematic analysis of elementary contexts (TAECs) and a word association analysis (WAA). RESULTS: The TAEC detected four thematic clusters related to two factors (temporal frame and contextual setting) that explained the variance among the narratives. The WAA evidenced a wide variety of emotions, both positive and negative, as patients reacted to the possibility of interrupting their therapy. CONCLUSIONS: A better understanding of patients' experiences can offer insights into promoting the development of more sustainable healthcare services and into therapeutic innovation aimed at improving patients' quality of life and at engaging them more in their treatment. The findings of this study can also help make medical professionals more aware of the patient's burden and help them identify potential interactions and emotional levers to improve clinical relationships.
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Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Medicina Narrativa/fisiologia , Qualidade de Vida/psicologia , Adulto , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Eosinophilic granulomatosis with polyangitis (EGPA) is an uncommon ANCA-associated systemic small-vessel necrotizing vasculitis. At times, EGPA presenting manifestations can be very different from the usually recognized disease patterns. We report a 52-year-old female patient with 3 years history of itching. During the time occurred a chronic skin lichenification on her legs and gradually developed a full-blown ANCA-MPO positive EGPA in combination with blood hypereosinophilia, eosinophilic vasculitis at skin biopsy, subclinical asthma and chronic rhinosinusitis.
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Síndrome de Churg-Strauss/complicações , Granulomatose com Poliangiite/complicações , Líquen Plano/etiologia , Doença Crônica , Síndrome de Churg-Strauss/diagnóstico , Feminino , Granulomatose com Poliangiite/diagnóstico , Humanos , Pessoa de Meia-IdadeRESUMO
PURPOSE: To evaluate the safety and intermediate-term efficacy of percutaneous microwave ablation (MWA) in primary and secondary liver tumors using a third generation MWA device, under ultrasound guidance. PATIENTS AND METHODS: Sixty-two patients (median age 74 years, 73â% males) with 69 liver tumors were enrolled in this prospective observational study. Forty-seven patients (76â%) had hepatocellular carcinoma (HCC) and 15 (24â%) metastases. Median follow-up was 3.6 years. RESULTS: Median tumor diameter at contrast enhanced computed tomography was 23âmm (I-III quartiles, 18â-â31âmm). All procedures were performed percutaneously using a 2.45 GHz generator. Median ablation time was 10 minutes (I-III quartiles, 10â-â14 minutes). A single percutaneous antenna insertion was performed for 56/69 (81â%) of the tumors. Technical success was obtained in all tumors. Primary efficacy at 24 hours was achieved in 68/69 (99â%) tumors. The overall one-year cumulative local tumor progression rate was 15.1â% (95â% CI, 7.7â-â24.8â%) with no significant difference between HCC and metastases (pâ=â0.26). There was one procedure-related mortality (1.6â%) and one major bleeding (1.6â%). CONCLUSION: Microwave ablation is a valid option for thermal ablation of HCC and liver metastases with comparable complication rate to other local ablative procedures.
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Ablação por Cateter/instrumentação , Ablação por Cateter/estatística & dados numéricos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Micro-Ondas/uso terapêutico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/prevenção & controle , Idoso , Ablação por Cateter/mortalidade , Estudos de Coortes , Desenho de Equipamento , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Neoplasias Hepáticas/diagnóstico por imagem , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Prevalência , Estudos Prospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Aim of the study is to investigate the use of antithrombotic drugs in older patients with atrial fibrillation (AF) at the time of hospital discharge. We enrolled 399 ≥65 years old patients with AF consecutively admitted to our acute geriatric unit from September 2012 to February 2014. Utilization of antithrombotic drugs, comorbidities, functional, mental and nutritional status were evaluated through a comprehensive geriatric assessment (CGA). A Logistic regression model was used to assess variables associated with antithrombotic use. On admission, 198 patients (49.6%) used oral anticoagulants (OAC), 125 (21.3%) antiplatelets, 32 (8%) low weight molecular heparin (LMWH) and 44 (11%) none of them. At discharge the proportion of patients on OAC increased to 55.7%. Age>90years (OR=2.57, CI=1.28-5.16, p-value=0.008), severe functional impairment (OR=3.38, CI=1.63-7.01, p-value=0.001), polypharmacy (OR=2.07, CI=1.1-3.86, p-value=0.023), HAS-BLED score (OR=1.64, CI=1.09-2.47, p-value=0.019) and ≥1 OAC contraindication (OR=5.01, CI=2.68-9.34, p-value<0.001) were all associated with OAC underuse. In conclusion, OAC is underused in geriatric patients with AF, while antiplatelet, LMWH and no antithrombotic therapy are relatively overused. Factors associated with the decision to not prescribe OAC lie on a mix of clinical and geriatric variables, among which functional status is particularly relevant.
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Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Uso de Medicamentos , Fibrinolíticos/uso terapêutico , Avaliação Geriátrica , Inibidores da Agregação Plaquetária/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Hospitalização , Humanos , Itália , Masculino , Polimedicação , Estudos Retrospectivos , Acidente Vascular Cerebral/prevenção & controleRESUMO
The primary objective of this study was to investigate whether the presence of comorbidities was associated with a lower health-related quality of life (HRQOL) in elderly patients with chronic myeloid leukemia (CML). A sample of 174 CML patients aged 60 years or above was analyzed. HRQOL was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). A number of pre-selected sociodemographic and disease-related factors were considered as potential confounding factors for the association between comorbidity and HRQOL. Mean age of the 174 patients analyzed was 70 years (range 60-87 years) and 55 % were male. Overall, 111 patients (64 %) reported at least one comorbidity. Analysis stratified by age group category showed a greater proportion of patients with comorbidities in the older sub-group population (≥70 years) compared to younger patients (60 to 69 years). Differences in HRQOL outcomes between patients with no comorbidity at all and those with two or more comorbid conditions were at least twice the magnitude of a clinically meaningful difference in all the physical and mental health scales of the SF-36. In multivariate analysis, after adjusting for key confounding factors, the following scales were significantly lower in those with comorbidity: general health (p < 0.001), bodily pain (p < 0.001), physical functioning (p = 0.002), and vitality (p = 0.002). Assessing comorbidity in elderly patients with CML is important to facilitate identification of those most in need of HRQOL improvements.
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Nível de Saúde , Inquéritos Epidemiológicos , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/psicologia , Qualidade de Vida/psicologia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Estudos Transversais , Feminino , Inquéritos Epidemiológicos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/epidemiologia , Doenças Musculoesqueléticas/psicologia , Dor/epidemiologia , Dor/psicologiaRESUMO
INTRODUCTION: Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are clonal disorders that present JAK2(V617F) mutation in 50-95% of cases. The main objective of this study was the comparison of two PCR methods, real-time (qPCR) and droplet digital PCR (DD-PCR) for detection of the JAK2(V617F) mutation, to assess analytic sensitivity, specificity, and feasibility of the two methods. METHODS: Ninety-nine patients with MPN of 225 presenting the JAK2(V617F) mutation by qPCR have been evaluated by DD-PCR also. RESULTS: We demonstrated an absolute concordance in terms of specificity between the two methods, DD-PCR showing a higher sensitivity (half a log higher than qPCR). As expected, a progressive increase of mutant allele burden was observed from essential thrombocythemia (ET) to polycythemia vera (PV) and primary myelofibrosis (PMF) to secondary myelofibrosis (SMF). CONCLUSION: In conclusion, our study showed that DD-PCR could represent a new and promising technological evolution for detection of JAK2 mutation in MPNs.
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Janus Quinase 2/genética , Mutação , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença Crônica , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/normas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/virologia , Vírus JC/fisiologia , Linfoma Folicular/virologia , Infecções por Polyomavirus/virologia , Infecções Tumorais por Vírus/virologia , Radioisótopos de Ítrio/uso terapêutico , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Quimiorradioterapia , Ensaios Clínicos como Assunto , Humanos , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/radioterapia , Linfoma Folicular/terapia , Compostos Radiofarmacêuticos/uso terapêutico , Rituximab , Ativação ViralRESUMO
The aim of the study was to investigate any possible influence of polymorphisms of transmembrane transporters human organic cation transporter 1 (hOCT1), ABCB1, ABCG2 on imatinib pharmacokinetics in 33 men and 27 women (median age and range, 56 and 27-79 years, respectively) affected by chronic myeloid leukemia. A population pharmacokinetic analysis was performed to investigate imatinib disposition in every patient and the role of transporter polymorphisms. Results showed that the α1-acid glycoprotein and the c.480C>G genotype of hOCT1 had a significant effect on apparent drug clearance (CL/F) being responsible, respectively, for a 20% and 10% decrease in interindividual variability (IIV) of CL/F (from 50.1 up to 19.6%). Interestingly, 25 patients carrying at least one polymorphic c.480 G allele had a significant lower CL/F value with respect to the 35 c.480CC individuals (mean±s.d., 9.6±1.6 vs 12.1±2.3 l h(-1), respectively; P<0.001). In conclusion, the hOCT1 c.480C>G SNP may significantly influence imatinib pharmacokinetics, supporting further analyses in larger groups of patients.
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Antineoplásicos/farmacocinética , Benzamidas/farmacocinética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Transportador 1 de Cátions Orgânicos/genética , Piperazinas/farmacocinética , Polimorfismo de Nucleotídeo Único , Pirimidinas/farmacocinética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Benzamidas/uso terapêutico , Feminino , Genótipo , Haplótipos , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Pirimidinas/uso terapêuticoRESUMO
Bendamustine demonstrated synergistic efficacy with bortezomib against multiple myeloma (MM) cells in vitro and seems an effective treatment for relapsed-refractory MM (rrMM). This phase II study evaluated bendamustine plus bortezomib and dexamethasone (BVD) administered over six 28-day cycles and then every 56 days for six further cycles in patients with rrMM treated with îº4 prior therapies and not refractory to bortezomib. The primary study end point was the overall response rate after four cycles. In total, 75 patients were enrolled, of median age 68 years. All patients had received targeted agents, 83% had 1-2 prior therapies and 33% were refractory to the last treatment. The response rateî¶partial response (PR) was 71.5% (16% complete response, 18.5% very good PR, 37% partial remission). At 12 months of follow-up, median time-to-progression (TTP) was 16.5 months and 1-year overall survival was 78%. According to Cox regression analysis, only prior therapy with bortezomib plus lenalidomide significantly reduced TTP (9 vs 17 months; hazard ratio=4.5; P=0.005). The main severe side effects were thrombocytopenia (30.5%), neutropenia (18.5%), infections (12%), neuropathy (8%) and gastrointestinal and cardiovascular events (both 6.5%). The BVD regimen is feasible, effective and well-tolerated in difficult-to-treat patients with rrMM.
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BACKGROUND: Besides tobacco and alcohol, dietary habits may have a relevant role in oral cavity and pharyngeal (OCP) cancer. METHODS: We analysed the role of selected food groups and nutrients on OCP cancer in a case-control study carried out between 1997 and 2009 in Italy and Switzerland. This included 768 incident, histologically confirmed squamous cell carcinoma cases and 2078 hospital controls. Odds ratios (ORs) were estimated using logistic regression models including terms for tobacco, alcohol and other relevant covariates. RESULTS: Significant inverse trends in risk were observed for all vegetables (OR=0.19, for the highest vs the lowest consumption) and all fruits (OR=0.39), whereas significant direct associations were found for milk and dairy products (OR=1.50), eggs (OR=1.71), red meat (OR=1.55), potatoes (OR=1.85) and desserts (OR=1.68), although trends in risk were significant only for potatoes and desserts. With reference to nutrients, significant inverse relations were observed for vegetable protein (OR=0.45, for the highest vs the lowest quintile), vegetable fat (OR=0.54), polyunsaturated fatty acids (OR=0.53), α-carotene (OR=0.51), ß-carotene (OR=0.28), ß-cryptoxanthin (OR=0.37), lutein and zeazanthin (OR=0.34), vitamin E (OR=0.26), vitamin C (OR=0.40) and total folate (OR=0.34), whereas direct ones were observed for animal protein (OR=1.57), animal fat (OR=2.47), saturated fatty acids (OR=2.18), cholesterol (OR=2.29) and retinol (OR=1.88). Combinations of low consumption of fruits and vegetables, and high consumption of meat with high tobacco and alcohol, led to 10- to over 20-fold excess risk of OCP cancer. CONCLUSION: Our study confirms and further quantifies that a diet rich in fruits and vegetables and poor in meat and products of animal origin has a favourable role against OCP cancer.
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Carcinoma de Células Escamosas/epidemiologia , Comportamento Alimentar , Alimentos , Neoplasias Bucais/epidemiologia , Neoplasias Faríngeas/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Adulto JovemRESUMO
Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurological side-effect of cancer treatment and may lead to declines in patients' daily functioning and quality of life. To date, there are no modern clinimetrically well-evaluated outcome measures available to assess disability in CIPN patients. The objective of the study was to develop an interval-weighted scale to capture activity limitations and participation restrictions in CIPN patients using the Rasch methodology and to determine its validity and reliability properties. A preliminary Rasch-built Overall Disability Scale (pre-R-ODS) comprising 146 items was assessed twice (interval: 2-3 weeks; test-retest reliability) in 281 CIPN patients with a stable clinical condition. The obtained data were subjected to Rasch analyses to determine whether model expectations would be met, and if necessarily, adaptations were made to obtain proper model fit (internal validity). External validity was obtained by correlating the CIPN-R-ODS with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) neuropathy scales and the Pain-Intensity Numeric-Rating-Scale (PI-NRS). The preliminary R-ODS did not meet Rasch model's expectations. Items displaying misfit statistics, disordered thresholds, item bias or local dependency were systematically removed. The final CIPN-R-ODS consisting of 28 items fulfilled all the model's expectations with proper validity and reliability, and was unidimensional. The final CIPN-R-ODS is a Rasch-built disease-specific, interval measure suitable to detect disability in CIPN patients and bypasses the shortcomings of classical test theory ordinal-based measures. Its use is recommended in future clinical trials in CIPN.
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Antineoplásicos/efeitos adversos , Avaliação da Deficiência , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Inquéritos e Questionários , Atividades Cotidianas , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Consenso , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Doenças do Sistema Nervoso Periférico/fisiopatologia , Doenças do Sistema Nervoso Periférico/psicologia , Valor Preditivo dos Testes , Qualidade de Vida , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
Intestinal acute GVHD (I-aGVHD) is a life-threatening complication after allografting. Non-invasive bed-side procedures to evaluate extension and treatment response are still lacking. We hypothesized that, during I-aGVHD, contrast-enhanced ultrasound sonography (CEUS) could detect microcirculation changes (MVC) of the bowel wall (BW) and help to monitor treatment response. We prospectively employed CEUS in 83 consecutive patients. Of these, 14 patients with biopsy-proven intestinal GVHD (I-GVHD) were defined as the study group, whereas 16 patients with biopsy-proven stomach GVHD (U-GVHD) without intestinal symptoms, 6 normal volunteers and 4 patients with neutropenic enterocolitis were defined as the control group. All patients were evaluated with both standard ultrasonography (US) and CEUS at the onset of intestinal symptoms, during clinical follow-up and at flare of symptoms. Standard US revealed BW thickening of multiple intestinal segments, useful to determine the extension of GVHD. CEUS showed MVC, which correlated with GVHD activity, treatment response, and predicted flare of intestinal symptoms. US and CEUS findings were superimposable at diagnosis and in remission. CEUS was, however, more sensitive and specific to identify subclinical activity in patients with clinical relevant improvement. These findings were not observed in the control groups. CEUS is a non-invasive, easily reproducible bed-side tool useful to monitor I-aGVHD.
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Doença Enxerto-Hospedeiro/diagnóstico por imagem , Enteropatias/diagnóstico por imagem , Doença Aguda , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Doença Enxerto-Hospedeiro/imunologia , Humanos , Enteropatias/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Homólogo/métodos , Ultrassonografia , Adulto JovemRESUMO
BACKGROUND: Splenic marginal zone lymphoma with or without villous lymphocytes (SLVL/SMZL) is an indolent lymphoma that typically affects elderly patients and that has a median survival >10 years. It presents with marked splenomegaly. Treatment is required in symptomatic cases. Splenectomy remains one of the first-line options in patients fit for surgery. The best pharmacological strategy has not yet been identified for poor surgical risk cases. Among different possible chemotherapeutic approaches, purine analogs, alone or in association with Rituximab, seem to be a valid therapeutic choice. PATIENTS AND METHODS: Fifty SMZL patients were treated with Cladribine ± anti-CD20 monoclonal antibody. RESULTS: Forty-seven of 50 patients were evaluable for response. ORR was 87%: 24 of 47 patients (51%) achieved a complete hematological response (CR), 17 of 47 (36%) a partial response (PR) and 6 (13%) resulted unresponsive. Interestingly, 15 of 24 cases (62%) in CR achieved also a molecular remission. After a median follow-up of 48 months, 7 of 41 responsive cases relapsed and the 5-year PFS was 80%. CONCLUSIONS: These data confirm the efficacy of this schedule emphasizing the impact of minimal residual disease even in the outcome of SMZL patients.
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Anticorpos Monoclonais Murinos/uso terapêutico , Antígenos CD20/imunologia , Cladribina/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Neoplasias Esplênicas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/efeitos adversos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cladribina/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasia Residual , Rituximab , Resultado do TratamentoRESUMO
The treatment of childhood B-cell-precursor ALL after isolated-extramedullary or late relapse is controversial. Most approaches are based on chemotherapy or allogeneic transplantation. The aim of this report is to assess the long-term outcome of children with 'low-risk' relapsed ALL treated according to a prospective purified auto-transplantation protocol. From January 1997 to March 2004, at a single pediatric Center, 30 ALL consecutive children, lacking an HLA-identical sibling, were treated according to the autologous purified peripheral blood stem cell protocol after isolated-extramedullary (7) or late medullary (24) relapse. After the 'DIAVE' mobilizing regimen a median of 11.6 × 10(6)CD34+/Kg (range 3.9-27.4) were collected. Leukaphereses were depleted by 99% of CD19+cells (range 98-100) by means of a double step immunological purification. The conditioning regimen included TBI. No early severe complications nor transplant-related deaths occurred; late effects, as expected, mostly consisted in endocrinological issues and were assessed at a median follow-up of 8.5 years. Five-year-EFS and survival were 68.5% (s.e. 7.9) and 85.7% (s.e. 5.9), respectively, for the 35 eligible patients and 70.0% (s.e. 8.4) and 86.7% (s.e. 6.2) for the 30 patients actually transplanted as per protocol. The outcome of this series favorably compares with historical data regarding both autologous transplantation and standard salvage chemotherapy.
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Transplante de Células-Tronco de Sangue Periférico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neoplasia Residual/diagnóstico , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Recidiva , Condicionamento Pré-Transplante , Transplante AutólogoRESUMO
Patients with mantle cell lymphoma (MCL) have a poor prognosis; consequently, new therapeutic approaches, such as rapamycin and its derivates, mammalian target of rapamycin (mTOR) inhibitors, are warranted. Temsirolimus (also known as CCI-779), a dihydroester of rapamycin, in MCL cell lines inhibited mTOR, downregulated p21 and v-Raf, and induced autophagy. The first clinical trial in MCL patients was performed using 250 mg of temsirolimus weekly for 6-12 cycles. The overall response rate was 38%; the median time to progression was 6.5 months, median overall survival was 12 months, and the median duration of response was 6.9 months. At lower dose (25 mg/week), the overall response rate was 41%, median overall survival was 14 months, and time to progression was 6 months. In another trial, 162 patients were randomly assigned to receive temsirolimus at 2 different doses (175 mg/week for 3 weeks, then 75 mg or 25 mg/week) or a treatment chosen by the investigator among the most frequently adopted single agents for treatment of relapsed MCL. Patients treated with 175/75 mg of temsirolimus had significantly higher response rates and longer progression-free survival than those treated with investigator's choice therapy. These data support the use of mTOR inhibitors for the treatment of MCL, probably in combination with other agents, such as antiangiogenic drugs or histone acetylase inhibitors.
RESUMO
AIMS: Morphology on bone marrow biopsy (BMB) samples has historically been the primary method used to detect bone marrow (BM) infiltration in B-cell non-Hodgkin's lymphoma (NHL), while fl ow cytometry (FC) and PCR assays have been generally used as ancillary methods. In this study we evaluated a combined approach utilizing all three methods to detect BM infiltration in patients with NHL both at diagnosis and after therapy. MATERIALS AND METHODS: We analyzed 193 patients with NHL, who received simultaneous BMB, FC and PCR assays. Morphology on histologic specimens was used to assess infiltration pattern and immunohistochemistry, FC to analyze immunophenotype, PCR to identify IgH rearrangement, BCL-1/JH and BCL-2/JH translocation. RESULTS: Morphology, FC and PCR assays agreed in 142 cases (73.5%) with more concordance at initial diagnosis than during postchemotherapy follow-up. PCR was the single best-performing test, while combination of morphology and PCR yielded a higher sensitivity than individual methods and was similar to PCR + FC. We observed little added benefit using a third approach. CONCLUSION: Given the initial importance of histological information evident by morphology, our data suggest that combination of morphology and PCR should be considered the gold standard for evaluation of BM infiltration at diagnosis, while combination of PCR + FC should be employed during post-treatment follow-up.
Assuntos
Medula Óssea/patologia , Neoplasias Ósseas/patologia , Citometria de Fluxo , Linfoma de Células B/patologia , Reação em Cadeia da Polimerase , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
In this study, we determined the allele and genotype frequencies of vascular endothelial growth factor (VEGF) G+405C, C-460T, C+936T and C-2578A single nucleotide polymorphisms (SNPs) in 32 patients affected by mantle cell lymphoma (MCL) and 58 healthy controls. Real-time PCR combined with melting curve analysis was used for the determination of SNP alleles. A significant difference in the allele frequency of VEGFC-460T and C+936T SNPs in MCL and healthy cases was not observed. On the contrary, VEGF G+405C and C-2578A SNP allele distribution was significantly lower in the patient group than among normal controls (p = 0.014, p = 0.001). This observation suggests that further investigation is warranted, both in vitro and in a larger series of patients, to further examine the role of VEGF polymorphisms in the pathogenesis of MCL. In addition, the use of quantitative real-time PCR combined with a melting curve analysis method in the detection of the 4 VEGF SNPs may have the potential to replace older and more time-consuming PCR-RFLP methods and bears further investigation.