RESUMEN
Refractory/early relapsed and 17p deletion/p53 mutation (del(17p)/TP53mut)-positive chronic lymphocytic leukemia (CLL) has been conventionally considered a high-risk disease, potentially eligible for treatment with allogeneic stem cell transplantation (alloSCT). In this multicenter retrospective analysis of 157 patients, we compared the outcomes of patients with high-risk CLL treated with alloSCT, a B-cell receptor pathway inhibitor (BCRi), and both. Seventy-one patients were treated with BCRis, 67 patients underwent reduced-intensity conditioning alloSCT, and 19 received alloSCT with a BCRi before and/or after transplantation. Inverse probability of treatment weighting analyses were performed to compare the alloSCT and no-alloSCT groups; in the 2 groups, 5-year OS, PFS, and cumulative incidence of nonrelapse mortality (NRM) and relapse were 40% versus 60% (Pâ¯=â¯.096), 34% versus 17% (Pâ¯=â¯.638), 28% versus 5% (Pâ¯=â¯.016), and 38% versus 83% (Pâ¯=â¯.005), respectively. Patients treated with alloSCT plus BCRi had a 3-year OS of 83%. The 3-year OS and NRM by year of alloSCT, including patients treated with BCRi, were 53% and 17% in 2000 to 2007, 55% and 30% in 2008 to 2012, and 72% and 18% in 2013 to 2018. In conclusion, the combination of pathway inhibitors and alloSCT is feasible and may further improve the outcome of high-risk CLL patients.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Linfocítica Crónica de Células B , Humanos , Leucemia Linfocítica Crónica de Células B/terapia , Estudios Retrospectivos , Trasplante de Células Madre , Acondicionamiento Pretrasplante , Trasplante Homólogo , Resultado del TratamientoRESUMEN
OBJECTIVE: Malignant ovarian germ cell tumors (MOGCT) carry an excellent prognosis, and the treatment aims to achieve results with the least possible treatment-related morbidity. The aim of this study was to assess the outcomes of pediatric patients with MOGCT. METHODS: Patients were treated according to their stage: surgery and surveillance for stage I; a modified bleomycin-etoposide-cisplatin (BEP) regimen for stages II (three cycles), III, and IV (three cycles) with surgery on residual disease. RESULTS: Seventy-seven patients were enrolled (median age 11.8 years), 26 with dysgerminoma (Dysg), 13 with immature teratoma and elevated serum alpha-fetoprotein levels (IT + AFP), and 38 with nondysgeminoma (Non-Dysg) staged as follows: 27 stage I, 13 stage II, 32 stage III, 5 stage IV. Among evaluable patients in stage I (5-year event-free survival [EFS] 72.1% [95% CI: 56.4-92.1%]; 5-year overall survival [OS] 100%), seven relapsed (three patients with Dysg and four patients with Non-Dysg) and were rescued with chemotherapy (plus surgery in three patients). Among the evaluable patients with stages II-IV, 48 (98%) achieved complete remission after chemotherapy ± surgery, one (IT + AFP, stage IV) had progressive disease. In the whole series (median follow-up 80 months), the 5-year OS and EFS were 98.5% (95% CI: 95.6-100%) and 84.5% (95% CI: 76.5-93.5%). CONCLUSIONS: We confirm the excellent outcome for MOGCT. Robust data are lacking on surgical staging, surveillance for Non-Dysg with stage I, the management of IT + AFP, and the most appropriate BEP regimen. As pediatric oncologists, we support the role of surveillance after proper surgical staging providing cases are managed by experts at specialized pediatric centers.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de Células Germinales y Embrionarias/terapia , Neoplasias Ováricas/terapia , Adolescente , Bleomicina/administración & dosificación , Niño , Preescolar , Cisplatino/administración & dosificación , Terapia Combinada , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Ováricas/patología , Ovariectomía , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVES: To describe changes in umbilical artery (UA) Doppler flow in monochorionic diamniotic (MCDA) twins affected by selective intrauterine growth restriction (sIUGR), to correlate Doppler findings with pregnancy course and perinatal outcome, and to report postnatal follow-up. METHODS: This was a retrospective study of 140 MCDA twins with sIUGR. UA end-diastolic flow, defined as Doppler waveform pattern Type I (persistently positive), Type II (persistently absent or persistently reversed) or Type III (intermittently absent or intermittently reversed), was recorded at first examination and monitored weekly until double or single intrauterine fetal death (IUFD), bipolar cord coagulation or delivery. All neonates had an early neonatal brain scan, magnetic resonance imaging, when indicated, and neurological assessment during infancy. Rates (per 100 person-weeks) and hazard ratios (HR) of IUFD in the IUGR twin in each pregnancy were calculated considering UA Doppler pattern as a time-dependent variable. RESULTS: At first examination, there were 65 cases with UA Doppler waveform pattern Type I, 62 with Type II and 13 with Type III. Of the 65 Type-I cases, 48 (74%) remained stable, while 17 (26%) changed to either Type II absent (14%), Type II reversed (9%) or Type III (3%). Of 62 Type-II cases (47 with absent and 15 with reversed flow), 33 (53%) remained stable (18 with absent and all 15 with reversed flow). The 29 Type-II absent cases which changed became Type II reversed (24/47, 51%) or Type III (5/47, 11%). All 13 Type-III cases remained stable. Compared with Type I, the risk of IUFD (adjusted for estimated fetal weight discordance and amniotic fluid deepest vertical pocket) was highest when the pregnancy was or became Type II reversed (HR, 9.5; 95% CI, 2.7-32.7) or Type II absent (HR, 4.3; 95% CI, 1.3-14.3). Mild neurological impairment was more prevalent in the IUGR twin than in the large cotwin (7% vs 1%, P = 0.02). CONCLUSIONS: Risk stratification based on UA Doppler is useful for planning ultrasound surveillance. However, patterns can change over time, with important consequences for management and outcome. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Asunto(s)
Enfermedades en Gemelos/diagnóstico por imagen , Retardo del Crecimiento Fetal/diagnóstico por imagen , Ultrasonografía Doppler/métodos , Ultrasonografía Prenatal/métodos , Arterias Umbilicales/diagnóstico por imagen , Adulto , Femenino , Humanos , Edad Materna , Valor Predictivo de las Pruebas , Embarazo , Resultado del Embarazo , Estudios Retrospectivos , Gemelos Monocigóticos , Adulto JovenRESUMEN
PURPOSE: An intensive therapeutic strategy for metastatic medulloblastoma was launched in 1998 in our Institution. The aim of this study was to examine the long-term quality of life (QoL) in survivor patients at least 3 years after the end of the treatment. METHODS: Patients were asked to complete self-administered QoL questionnaires. An index of physical impairment (IPI) was scored (range 0-100; the lower the score the better) based on clinical objective observations. Patients were divided into two groups (lower IPI group, and higher IPI group) and descriptively compared accordingly. RESULTS: The study was completed by 25/33 eligible patients. Despite patients with a higher IPI reported worse perceived health condition, they had better emotional and psychological scores than those with a lower IPI in all QoL questionnaires. CONCLUSION: In our sample, patients with more severe objective and perceived physical impairments reported a better psychosocial QoL, possibly because the greater attention paid to them by society and family contributes to a better adjustment in long-term survivors. On this base, it should be recommended that all survivors receive a strong support as the most impaired patients.
Asunto(s)
Neoplasias Cerebelosas/radioterapia , Meduloblastoma/radioterapia , Radioterapia/efectos adversos , Sobrevivientes/psicología , Adolescente , Niño , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Masculino , Calidad de Vida , Radioterapia/métodos , Encuestas y CuestionariosRESUMEN
Epigenetics is believed to play a role in Alzheimer's disease (AD). DNA methylation, the most investigated epigenetic hallmark, is a reversible mechanism that modifies genome function and chromosomal stability through the addition of methyl groups to cytosine located in CpG dinucleotides to form 5 methylcytosine (5mC). Methylation status of repetitive elements (i.e. Alu, LINE-1 and SAT-α) is a major contributor of global DNA methylation patterns and has been investigated in relation to a variety of human diseases. However, the role of methylation of repetitive elements in blood of AD patients has never been investigated so far. In the present study, a quantitative bisulfite-PCR pyrosequencing method was used to evaluate methylation of Alu, LINE-1 and SAT-α sequences in 43 AD patients and 38 healthy donors. In multivariate analysis adjusting for age and gender, LINE-1 was increased in AD patients compared with healthy volunteers (ADs: 83.6%5mC, volunteers: 83.1%5mC, p-value: 0.05). The group with best performances in mini mental state examination (MMSE) showed higher levels of LINE-1 methylation compared to the group with worst performances (MMSE>22: 83.9%5mC; MMSE≤22: 83.2%5mC; p=0.05). Our data suggest that LINE-1 methylation may lead to a better understanding of AD pathogenesis and course, and may contribute to identify novel markers useful to assess risk stratification. Further prospective investigations are warranted to evaluate the dynamics of DNA methylation from early-stage AD to advanced phases of the disease.
Asunto(s)
Elementos Alu/genética , Enfermedad de Alzheimer/genética , Metilación de ADN , ADN Satélite/genética , Elementos de Nucleótido Esparcido Largo/genética , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/psicología , Péptidos beta-Amiloides/líquido cefalorraquídeo , Apolipoproteínas E/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fosforilación , Procesamiento Proteico-Postraduccional , Pruebas Psicológicas , Proteínas tau/líquido cefalorraquídeoRESUMEN
INTRODUCTION: Asphalt workers are potentially exposed to polycyclic aromatic hydrocarbons (PAHs). As some PAHs are classified as carcinogenic, the assessment of occupational exposure to these agents is of the utmost importance in preventing toxic effects. OBJECTIVES: To assess exposure to PAHs by urinary 1-hydroxypyrene (1-OHPyr). METHODS: We studied 22 asphalt workers (14 smokers) and 5 control subjects (1 smoker). Multiple samples of urine (up to 4per subject) were collected at the end of the shift for the measurement of 1-OHPyr by LCMS/MS. Univariate and multivariate linear models for repeated measurements were used to evaluate the differences between groups and to identify the variables influencing of exposure. RESULTS: The median urinary excretion of 1-OHPyr in asphalt workers was low, but higher than that of control subjects (184 vs. <20 ng/L, or 106 vs. <20 ng/g creatinine, p < 0.001); cigarette smoking marginally increased 1-OHPyr in smoking asphalt workers in comparison to non-smokers (129 vs. 208 ng/L p= 0.09 or 94 vs. 121 ng/g creatinine, p = 0.06). The number of consecutive days at work significantly influenced the urinary excretion of l-OHPyr [+59% every day, CI: (2, 147), p = 0.04]. Subjects using paving machines had the highest exposure. A strong association between 1-OHPyr and urinary creatinine was observed. CONCLUSIONS: urinary 1-OHPyr is a useful indicator of occupational exposure to low levels of PAHs, such as those found in the subjects studied; in using this biomarker it is recommended to collect urine samples at the end of the working week and to express levels of the biomarker corrected for urinary creatinine.
Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Hidrocarburos , Mutágenos/metabolismo , Exposición Profesional , Hidrocarburos Policíclicos Aromáticos/toxicidad , Pirenos/metabolismo , Adulto , Contaminantes Ocupacionales del Aire/orina , Análisis de Varianza , Biomarcadores/orina , Estudios de Casos y Controles , Monitoreo del Ambiente/métodos , Monitoreo Epidemiológico , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Exposición Profesional/análisis , Hidrocarburos Policíclicos Aromáticos/orina , Medición de Riesgo , Factores de Riesgo , Fumar/efectos adversosRESUMEN
BACKGROUND: Aim of this study was to compare early graft function after transplantation of recipients transplanted with livers procured from donors after brain death who experienced transient or sustained cardio-circulatory collapse. METHODS: We retrospectively analysed patients who underwent liver transplantation (LTx) at our Institution from January 2010 to May 2012. Recipients were divided into 3 groups: those who received livers from brain death donors who experienced reversible cardio-circulatory arrest before organ procurement (RCA); those who experienced sustained cardio-circulatory collapse, treated with extra-corporeal membrane oxygenation support as rescue therapy of refractory cardiogenic shock (ECMO). Standard donors were considered as reference group (REF). Postoperative graft function, Primary Non-Function (PNF), and complications during the first 30 days were analysed. RESULTS: 102 LTx were analysed (76 REF, 22 RCA and 4 ECMO). The main cause of donor's death was post-anoxic coma in RCA and ECMO, cerebrovascular accident in REF. SGOT in REF, RCA, and ECMO donors were 27 [17-43], 54 [34-92], 716 [190-962] respectively, SGPT 17 [12-34], 46 [27-73], 84 [51-175] UI/L respectively, both P<0.01. All recipients had similar SGOT (P=0.48), SGPT (P=0.75) and Model for End-Stage Liver Disease scores (P=0.98) before LTx; similar graft cold and warm ischemia time and serum lactate levels at the end of surgery. After LTx, Intensive Care Unit stay and the incidence of PNF were similar. CONCLUSION: The use of livers procured from donors after brain death that experienced transient or sustained cardio-circulatory collapse was associated with early graft function comparable to that of standard donors.