RESUMO
Despite the long history of bendamustine as treatment for indolent non-Hodgkin lymphoma, long-term efficacy and toxicity data are minimal. We reviewed long-term data from three clinical trials to characterize the toxicity and efficacy of patients receiving bendamustine. Data were available for 149 subjects at 21 sites. The median age was 60 years at the start of bendamustine (range 39-84), and patients had received a median of 3 prior therapies. The histologies included grades 1-2 follicular lymphoma (FL; n = 73), grade 3 FL (n = 23), small lymphocytic lymphoma (n = 20), marginal zone lymphoma (n = 15), mantle cell lymphoma (n = 9), transformed lymphomas (n = 5), lymphoplasmacytic lymphoma (n = 2) and not reported (n = 2). The median event-free survival was 14·1 months. Nine of 12 attempted stem cell collections were successful. With a median follow-up of 8·9 years, 23 patients developed 25 cancers, including 8 patients with myelodysplastic syndrome/acute myeloid leukaemia. These data provide important information regarding the long-term toxicity of bendamustine in previously treated patients. A small but meaningful number of patients achieved durable remissions following bendamustine. These rigorously collected, patient-level, long-term follow-up data provide reassurance that bendamustine or bendamustine plus rituximab is associated with efficacy and safety for patients with relapsed or refractory indolent non-Hodgkin lymphoma.
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Antineoplásicos Alquilantes/administração & dosagem , Cloridrato de Bendamustina/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cloridrato de Bendamustina/efeitos adversos , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Síndromes Mielodisplásicas/induzido quimicamente , Segunda Neoplasia Primária/induzido quimicamente , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
Histone deacetylase inhibitors are members of a class of epigenetic drugs that have proven activity in T-cell malignancies, but little is known about their efficacy in B-cell lymphomas. Abexinostat is an orally available hydroxamate-containing histone deacetylase inhibitor that differs from approved inhibitors; its unique pharmacokinetic profile and oral dosing schedule, twice daily four hours apart, allows for continuous exposure at concentrations required to efficiently kill tumor cells. In this phase II study, patients with relapsed/refractory non-Hodgkin lymphoma or chronic lymphocytic leukemia received oral abexinostat at 80 mg BID for 14 days of a 21-day cycle and continued until progressive disease or unacceptable toxicity. A total of 100 patients with B-cell malignancies and T-cell lymphomas were enrolled between October 2011 and July 2014. All patients received at least one dose of study drug. Primary reasons for discontinuation included progressive disease (56%) and adverse events (25%). Grade 3 or over adverse events and any serious adverse events were reported in 88% and 73% of patients, respectively. The most frequently reported grade 3 or over treatment-emergent related adverse events were thrombocytopenia (80%), neutropenia (27%), and anemia (12%). Among the 87 patients evaluable for efficacy, overall response rate was 28% (complete response 5%), with highest responses observed in patients with follicular lymphoma (overall response rate 56%), T-cell lymphoma (overall response rate 40%), and diffuse large B-cell lymphoma (overall response rate 31%). Further investigation of the safety and efficacy of abexinostat in follicular lymphoma, T-cell lymphoma, and diffuse large B-cell lymphoma implementing a less dose-intense week-on-week-off schedule is warranted. (Trial registered at: EudraCT-2009-013691-47).
Assuntos
Benzofuranos/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzofuranos/efeitos adversos , Diarreia/induzido quimicamente , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Inibidores de Histona Desacetilases/efeitos adversos , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Ácidos Hidroxâmicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Trombocitopenia/induzido quimicamente , Resultado do TratamentoRESUMO
We compared the health-related quality-of-life of patients with newly diagnosed multiple myeloma aged over 65 years or transplant-ineligible in the pivotal, phase III FIRST trial. Patients received: i) continuous lenalidomide and low-dose dexamethasone until disease progression; ii) fixed cycles of lenalidomide and low-dose dexamethasone for 18 months; or iii) fixed cycles of melphalan, prednisone, thalidomide for 18 months. Data were collected using the validated questionnaires (QLQ-MY20, QLQ-C30, and EQ-5D). The analysis focused on the EQ-5D utility value and six domains pre-selected for their perceived clinical relevance. Lenalidomide and low-dose dexamethasone, and melphalan, prednisone, thalidomide improved patients' health-related quality-of-life from baseline over the duration of the study across all pre-selected domains of the QLQ-C30 and EQ-5D. In the QLQ-MY20, lenalidomide and low-dose dexamethasone demonstrated a significantly greater reduction in the Disease Symptoms domain compared with melphalan, prednisone, thalidomide at Month 3, and significantly lower scores for QLQ-MY20 Side Effects of Treatment at all post-baseline assessments except Month 18. Linear mixed-model repeated-measures analyses confirmed the results observed in the cross-sectional analysis. Continuous lenalidomide and low-dose dexamethasone delays disease progression versus melphalan, prednisone, thalidomide and has been associated with a clinically meaningful improvement in health-related quality-of-life. These results further establish continuous lenalidomide and low-dose dexamethasone as a new standard of care for initial therapy of myeloma by demonstrating superior health-related quality-of-life during treatment, compared with melphalan, prednisone, thalidomide.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Nível de Saúde , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Dexametasona/administração & dosagem , Feminino , Humanos , Lenalidomida , Masculino , Melfalan/administração & dosagem , Mieloma Múltiplo/psicologia , Prednisona/administração & dosagem , Qualidade de Vida/psicologia , Talidomida/administração & dosagem , Talidomida/análogos & derivadosRESUMO
To evaluate the diagnostic accuracy of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) and Endoscopic Ultrasound-guided Fine Needle Aspiration (EUS-FNA) in the diagnosis of lymphoma. A retrospective analysis of patients with suspected mediastinal lymphoproliferative disorders who underwent EBUS-TBNA, EUS-FNA or combined procedures from 2009 to 2019 was conducted using a prospectively maintained interventional thoracic endoscopy database. Demographic data, imaging, needle size, surgical biopsy, complications rate and pathology reports were reviewed. Over a 10-year period, a total of 444 patients were investigated with endosonography as the first diagnostic procedure for mediastinal adenopathy suspicious for lymphoma. Lymphoma was diagnosed in 77 patients (17.3%). In total, 68 patients (88.3%) were diagnosed using endosonographic mediastinal tissue sampling. Four patients had both lymphoproliferative disorders and lung cancer. Nine patients (11.7%) required a surgical biopsy to confirm the lymphoma diagnosis (6 non-diagnostic; 3 inadequate samples from endosonographic biopsies). In patients with adequate biopsies via endosonography, the sensitivity for the diagnosis of lymphoma, was 91.9% (n = 68/74). The histopathologic subtype of lymphoma was determined by endosonographic biopsies in 61 patients (89.7%) with an increased sensitivity (92.6%) for low grade Non-Hodgkin lymphoma (NHL). No acute complication related to endosonography was observed. Endosonographic biopsy (EBUS and/or EUS) of mediastinal adenopathy in patients with suspected lymphoma is a highly sensitive and safe diagnostic test. Endosonography should be the first test in the diagnosis of suspicious mediastinal lymphoma and should be followed by surgical biopsy in cases of insufficient sampling or indefinite diagnosis.
Assuntos
Neoplasias Pulmonares , Linfadenopatia , Linfoma , Broncoscopia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Endossonografia/métodos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Linfadenopatia/patologia , Linfoma/diagnóstico por imagem , Linfoma/patologia , Mediastino/diagnóstico por imagem , Mediastino/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
BACKGROUND: Immunoglobulin light chain (AL) amyloidosis is a complex disease marked by a poor clinical portrait and prognosis generally leading to organ dysfunction and shortened survival. We aimed to review the available evidence on whether AL amyloidosis can lead to malnutrition, thus having a negative impact on quality of life (QoL) and survival. MATERIALS: We searched Pubmed for studies that assessed malnutrition in amyloidosis patients, with no restrictions to the year of publication or language. Retrospective or prospective, observational, and interventional studies that reported data regarding AL amyloidosis and nutritional status were included. RESULTS: From 62 articles retrieved, 23 were included. Malnutrition was prevalent in up to 65% of patients with AL Amyloidosis. Prevalence of weight loss of 10% or more ranged from 6 to 22% of patients, while a body mass index of < 22 kg/m2 was found in 22 to 42%. Weight loss, lower BMI and other indicators of poor nutritional status were negatively associated with quality of life and survival. Only one RCT focused on nutritional counseling was found and reported positive results on patients QoL and survival. CONCLUSION: Despite inconsistencies across assessment criteria, the available data reveal that weight loss and malnutrition are common features in patients with AL amyloidosis. This review reinforces the premise that an impaired nutritional status can be negatively associated with QoL and survival in patients with AL amyloidosis, and therefore should be further investigated.
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Amiloidose , Amiloidose de Cadeia Leve de Imunoglobulina , Desnutrição , Amiloidose/complicações , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Desnutrição/etiologia , Estado Nutricional , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Redução de PesoRESUMO
Context: The SELECT trial led to the approval of lenvatinib for the treatment of advanced radioiodine-refractory differentiated thyroid carcinomas (DTCs) but also revealed an important adverse event (AE) profile which may limit its use in clinical practice. Objective: We aim to describe the efficacy and toxicity profiles of lenvatinib in real life. Methods: We included all patients who received lenvatinib for an advanced DTC at our institution, enrolling 27 patients. We reviewed retrospectively electronic medical records to assess efficacy and AEs. Results: Among the 24 patients with evaluation of tumor response during treatment, overall response rate (ORR) was 37.0% (95% CI, 19.4%-57.6%), and disease control rate was 85.2% (95% CI, 66.3%-95.8%). The median progression-free survival (PFS) was 12 months (95% CI, 7.5-16.5]. The most prevalent AEs were hypertension (77.8%), fatigue (55.6%), and weight loss (51.9%). At least one gradeâ ≥â 3 AE was experienced by 25/27 patients (92.6%), mostly hypertension (59.3%). Lenvatinib was discontinued due to AEs in 13/27 patients (48.1%). Interestingly, 1 patient experienced a grade 4 posterior reversible encephalopathy syndrome, and another developed a Takotsubo cardiomyopathy. Conclusion: The safety profile of lenvatinib in our cohort was similar to that reported in the literature, with a predominance of hypertension. Rigorous blood pressure control is therefore essential to avoid discontinuing therapy. We also report 2 severe and rarely described AEs that physicians should watch for. As for efficacy, although less than in the SELECT trial, ORR and PFS were similar to other real-life studies.
RESUMO
Medulloblastoma is an aggressive primary brain tumor that is extremely rare in adults; therefore, prospective studies are limited. We reviewed the information of all MB patients treated at the CHUM between 2006 and 2017. We divided our cohort by age and further divided adult patients (53%) in two groups, those diagnosed between 2006-2012 and 2013-2017. In our adult population, median follow up was 26 months and SHH-activated MB comprised 39% of tumors. Adult 5yOS was 80% and first-line therapy led to a 5yPFS of 77%. The absence of radiosensitizing chemotherapy (100% vs. 50%; p = 0.033) negatively influenced 5yPFS. 96% of adult patients received radiotherapy and 48% of them received concomitant radiosensitizing chemotherapy. Complete surgical resection was performed on 85% of adults, but the extent of resection did not have a discernable impact on survival and did not change with time. Adjuvant chemotherapy did not clearly affect prognosis (5yOS 80% vs. 67%, p = 0.155; 5yPFS 78% vs. 67%, p = 0.114). From 2006-2012, the most common chemotherapy regimen (69%) was Cisplatinum, Lomustine and Vincristine, which was replaced in 2013 by Cisplatinum, Etoposide and Cyclophosphamide (77%) with a trend for worse survival. Nine patients recurred and seven of these (78%) were treated with palliative chemotherapy. In conclusion, we did not identify prognostic demographic or tumor factors in our adult MB population. The presence of radiosensitizing chemotherapy was associated with a more favorable PFS. Cisplatinum, Lomustine and Vincristine regimen might be a better adjuvant chemotherapy regimen.
Assuntos
Neoplasias Cerebelares , Meduloblastoma , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Canadá , Neoplasias Cerebelares/epidemiologia , Neoplasias Cerebelares/terapia , Demografia , Humanos , Meduloblastoma/tratamento farmacológico , Meduloblastoma/terapia , Recidiva Local de Neoplasia , Estudos Prospectivos , UniversidadesRESUMO
It is unclear if immunosuppression increases the likelihood of malignant transformation of monoclonal gammopathy of undetermined significance (MGUS) and whether adverse renal outcomes in kidney transplant recipients with MGUS are more frequent. METHODS: We performed a retrospective cohort study of kidney transplant recipients at the Centre Hospitalier de l'Université de Montréal between 2000 and 2016. RESULTS: Among 755 study participants, 13 (1.7%) were found to have MGUS before transplant. Two evolved to smoldering multiple myeloma and 2 presented paraprotein-induced allograft injury from light chain deposition disease. Forty-six patients developed posttransplant MGUS (2.5% 5-y cumulative incidence) of which 1 progressed to multiple myeloma and 1 experienced kidney allograft loss from light chain deposition disease. None of the patients with a malignant transformation or paraprotein-induced renal disease after transplantation had had a systematic workup before transplantation to exclude hematologic malignancies and paraprotein-related kidney injury. Nine posttransplant MGUS (21%) were transient. Multivariable analysis revealed that age at transplant (hazard ratio 1.05 per 1-y increase, 95% confidence intervals, 1.02-1.08) and prior cytomegalovirus infection (hazard ratio 2.22, 95% confidence intervals, 1.07-4.58) were associated with the development of MGUS after transplantation. Of 7 posttransplant lymphoproliferative disorders, none were preceded by MGUS. CONCLUSIONS: Our results suggest that the identification of MGUS in a transplant candidate should lead to further investigations to exclude a plasma cell neoplasm and monoclonal gammopathy of renal significance before transplantation. MGUS arising after transplantation appears to carry a favorable evolution.
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In a retrospective study, 32 patients with myotonic dystrophy, including congenital (n=17) and infantile/juvenile forms (n=15) were studied during a long follow-up lasting 7-28 years (median: 17 years). The clinical presentation was extremely variable; however, a continuum did exist between severe and less severe congenital forms, and later-onset forms, without genotype-phenotype correlation. We observed some unusual presentations, such as 3 cases of isolated club-feet during the neonatal period, and 7 patients (23%) with a completely isolated mental deficiency, language delay and school failure, who only completed the clinical picture several years later. Wechsler scale testing was performed in all cases, and repeated with 8 patients. It demonstrated a decrease in intellectual abilities in 5 patients, suggesting the possibility of a degenerative cerebral process occurring in these children. This decrease has also been reported in some adult cases. This study illustrates the extremely heterogeneous clinical presentation of myotonic dystrophy in childhood.
Assuntos
Distrofia Miotônica/fisiopatologia , Fenótipo , Adolescente , Adulto , Criança , Pré-Escolar , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/etiologia , Progressão da Doença , Genótipo , Humanos , Masculino , Distrofia Miotônica/complicações , Distrofia Miotônica/genética , Testes Neuropsicológicos , Estudos Retrospectivos , Tempo , Escalas de WechslerRESUMO
BACKGROUND: Neuroblastoma, the most common extracranial solid tumor that occurs in early childhood, can be identified in the preclinical stages by the detection of catecholamines in the urine. However, it is unknown whether routine screening for neuroblastoma reduces mortality due to this disease. METHODS: Through their parents, we offered screening for neuroblastoma at three weeks and six months of age to all 476,654 children born in the province of Quebec, Canada, during a five-year period (May 1, 1989, through April 30, 1994). The participation rate was 92 percent. The rate of death due to neuroblastoma was determined and compared with the rates in several unscreened control populations born during the same period. RESULTS: Among children younger than eight years of age in the Quebec cohort, there were 22 deaths due to neuroblastoma; the cumulative (+/-SE) mortality rate due to neuroblastoma was 4.78+/-1.14 per 100,000 children over a period of nine years. The standardized incidence ratios for death due to neuroblastoma for the Quebec cohort were 1.11 (95 percent confidence interval, 0.64 to 1.92) as compared with a control group in Ontario, Canada; 0.90 (95 percent confidence interval, 0.48 to 1.70) as compared with a control group in Minnesota; 1.40 (95 percent confidence interval, 0.81 to 2.41) as compared with a control group in Florida; and 0.96 (95 percent confidence interval, 0.56 to 1.66) as compared with a control group in the Greater Delaware Valley. The standardized mortality ratio for the Quebec cohort as compared with the rest of Canada was 1.39 (95 percent confidence interval, 0.85 to 2.30); the odds ratio for the comparison with a cohort born in Quebec before the screening program began was 0.98 (95 percent confidence interval, 0.54 to 1.77). CONCLUSIONS: Screening infants for neuroblastoma does not appear to reduce mortality due to this disease.
Assuntos
Programas de Rastreamento , Neuroblastoma/mortalidade , Canadá/epidemiologia , Estudos de Casos e Controles , Catecolaminas/metabolismo , Criança , Pré-Escolar , Feminino , Seguimentos , Ácido Homovanílico/urina , Humanos , Lactente , Recém-Nascido , Masculino , Triagem Neonatal , Estadiamento de Neoplasias , Neuroblastoma/diagnóstico , Neuroblastoma/prevenção & controle , Quebeque/epidemiologia , Estados Unidos/epidemiologia , Ácido Vanilmandélico/urinaRESUMO
BACKGROUND: Pediatric arterial ischemic stroke remains incompletely understood. Population-based epidemiological data inform clinical trial design but are scant in this condition. We aimed to determine age-specific epidemiological characteristics of arterial ischemic stroke in neonates (birth to 28 days) and older children (29 days to 18 years). METHODS: We conducted a 16-year, prospective, national population-based study, the Canadian Pediatric Ischemic Stroke Registry, across all 16 Canadian acute care children's hospitals. We prospectively enrolled children with arterial ischemic stroke from January 1992 to December 2001 and documented disease incidence, presentations, risk factors, and treatments. Study outcomes were assessed throughout 2008, including abnormal clinical outcomes (stroke-related death or neurological deficit) and recurrent arterial ischemic stroke or transient ischemic attack. RESULTS: Among 1129 children enrolled with arterial ischemic stroke, stroke incidence was 1.72/100,000/year, (neonates 10.2/100,000 live births). Detailed clinical and radiological information were available for 933 children (232 neonates and 701 older children, 55% male). The predominant clinical presentations were seizures in neonates (88%), focal deficits in older children (77%), and diffuse neurological signs (54%) in both. Among neonates, 44% had no discernible risk factors. In older children, arteriopathy (49% of patients with vascular imaging), cardiac disorders (28%), and prothrombotic disorders (35% of patients tested) predominated. Antithrombotic treatment increased during the study period (P < 0.001). Stroke-specific mortality was 5%. Outcomes included neurological deficits in 60% of neonates and 70% of older children. Among neonates, deficits emerged during follow-up in 39%. Overall, an initially decreased level of consciousness, a nonspecific systemic presentation, and the presence of stroke risk factors predicted abnormal outcomes. For neonates, predictors were decreased level of consciousness, nonspecific systemic presentation, and basal ganglia infarcts. For older children, predictors were initial seizures, nonspecific systemic presentation, risk factors, and lack of antithrombotic treatment. Recurrent arterial ischemic stroke or transient ischemic attack developed in 12% of older children and was predicted by arteriopathy, presentation without seizures, and lack of antithrombotic treatment. Emerging deficit was predicted by neonatal age at stroke and by cardiac disease. CONCLUSIONS: This national data set provides a population-based disease incidence rate and demonstrates the protective effect of antithrombotic treatment in older children, and frequent long-term emerging deficits in neonates and in children with cardiac disorders. Further clinical trials are required to develop effective age-appropriate treatments for children with acute arterial ischemic stroke.
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Isquemia Encefálica/epidemiologia , Isquemia Encefálica/terapia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Adolescente , Canadá/epidemiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Resultado do TratamentoRESUMO
A sensitive and accurate stable isotope dilution GC/MS assay was developed and validated for the quantification of succinylacetone (SA) in plasma and amniotic fluid (AF). SA is pathognonomic for tyrosinemia type I, a genetic disorder caused by a reduced activity of fumarylacetoacetate hydrolase (FAH). In untreated patients, SA can easily be measured in plasma and urine because the expected concentrations are in the micromol/L range. Due to a founder effect, the province of Quebec has an unusually high prevalence of tyrosinemia type I, hence, the quantification of SA in AF or plasma of treated patients in the nmol/L range becomes very useful. The method utilizes 13C5-SA as an internal standard and a three-step sample treatment consisting of oximation, solvent extraction and TMCS derivatization. The assay was validated by recording the ion intensities of m/z 620 for SA and m/z 625 for ISTD in order to demonstrate the precision of measurements, the linearity of the method, limit of quantification and detection (LOQ and LOD), specificity, accuracy, as well as metabolite stability. Values for the intra-day assays ranged from 0.2 to 3.2% while values for the inter-day assays ranged from 1.9 to 5.6% confirming that the method has good precision. A calibration plot using SA detected by GC/MS gave excellent linearity with a correlation coefficient of 0.999 over the injected concentration range of 5-2000 nmol/L. LOQ and LOD were 3 and 1 nmol/L, respectively. The usefulness of this method was demonstrated by SA quantification in an AF sample of an affected fetus and in plasma of patients treated with NTBC. The results demonstrate that this novel GC/MS method may be a valuable tool for metabolic evaluation and clinical use.
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Líquido Amniótico/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Heptanoatos/análise , Tirosinemias/diagnóstico , Heptanoatos/sangue , Humanos , Monitorização Fisiológica , Nanotecnologia , Reprodutibilidade dos Testes , Tirosinemias/sangue , Tirosinemias/fisiopatologiaRESUMO
Radiolabelled monoclonal antibodies (MAbs) differ from naked MAbs because they usually use murine antibodies, however, the next generation will use humanised MAb. Currently two compounds have been widely tested and both have been registered in the USA (yttrium-90 ibritumomab tiuxetan (Zevalin; Idec Pharmaceuticals) and iodine-131 tositumomab formerly known as (131)I-anti-B1 (Bexxar; Corixa Corp.)). The first one has recently been registered in Europe. Both MAbs have activity for the treatment of follicular lymphoma (FL) but few studies have been done outside this indication. In FL, they are associated with a higher response rate than rituximab. Their best indication is currently for patients who are refractory to rituximab but studies are running to define other indications.
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Linfoma não Hodgkin/tratamento farmacológico , Radioimunoterapia/métodos , Anticorpos Monoclonais/uso terapêutico , Humanos , Linfoma não Hodgkin/radioterapia , Resultado do TratamentoRESUMO
The purpose of this study was to evaluate retrospectively the effect of a second treatment with rituximab for patients who progressed after a response to a first treatment. We analysed the charts of 41 patients treated at CHU Lyon-Sud between 1997 and May 2003. Patients were treated with rituximab alone or with a combination of rituximab and chemotherapy. The overall response rate (complete and partial response) was 73% for the second treatment. The median time to progression was longer but not significant for the second treatment in comparison with the first one (15.2 versus 11.3 months, P = 0.09). The second treatment was well tolerated. Thus, a second treatment with rituximab should be considered, alone or in combination with chemotherapy, for patients who progress after a first response to rituximab.
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Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Linfócitos B/efeitos dos fármacos , Linfoma de Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos B/patologia , Feminino , França , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Estudos Retrospectivos , Rituximab , Resultado do TratamentoRESUMO
Alemtuzumab, the monoclonal anti-CD52 antibody, has clinical activity in B-cell and T-cell malignancies at the dose of 30 mg three times weekly for 9-12 weeks. This standard regimen induced responses usually shorter than 6 months. To prolong time to progression, we initialized a phase II study with an identical initial scheme until partial response, followed by a maintenance therapy lasting at least 4 months. Eleven heavily pretreated patients (8 with B-chronic lymhocytic leukemia (B-CLL) and 3 with small lymphoctyic lymphoma (SLL)) have been treated with this maintenance regimen (MR patients) and were retrospectively compared to 5 patients (3 B-CLL and 2 SLL) treated with the standard regimen (SR patients). Patients characteristics before treatment were identical in both groups. Objective response was reached by 9 (82%) MR patients and 3 (60%) SR patients (p NS). After the treatment, 8 (73%) MR patients and all SR patients progressed with a median time at 12.2 months and 3 months respectively. Survival time from alemtuzumab was significatively different (P < 0.005). None of the patients died in the MR group with a median follow-up at 16 months. In the SR group, the median survival from alemtuzumab was 5.9 months. We did not observe any differences in terms of hematological toxicites and infections between the two groups. In conclusion, maintenance alemtuzumab therapy seems to increase the time to progression and the survival, without adding hematological toxicities and infectious complications. More patients are needed to confirm this observation.
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Anticorpos Monoclonais/administração & dosagem , Anticorpos Antineoplásicos/administração & dosagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Alemtuzumab , Anticorpos Monoclonais/toxicidade , Anticorpos Monoclonais Humanizados , Anticorpos Antineoplásicos/toxicidade , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/induzido quimicamente , Indução de Remissão/métodos , Terapia de Salvação/métodos , Análise de SobrevidaAssuntos
Anemia/fisiopatologia , Hiperplasia do Linfonodo Gigante/cirurgia , Mesentério/patologia , Doenças Peritoneais/cirurgia , Adulto , Anemia/etiologia , Biópsia por Agulha , Análise Química do Sangue , Hiperplasia do Linfonodo Gigante/complicações , Hiperplasia do Linfonodo Gigante/patologia , Feminino , Humanos , Hialina/metabolismo , Imuno-Histoquímica , Laparotomia/métodos , Doenças Peritoneais/complicações , Doenças Peritoneais/patologia , Remissão Espontânea , Medição de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Use of combination antiretroviral therapy (cART) and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with or without rituximab for treatment of diffuse large B-cell lymphoma (DLBCL) in HIV substantially increases response rates but may also increase toxicity, possibly due to antiretroviral-antineoplastic drug interactions. The objective of this study was to evaluate the frequency of complete remission (CR) of DLBCL in patients treated with CHOP while receiving a protease inhibitor (PI) versus a non-PI-based cART. METHODS: A retrospective multicentre pilot study was conducted in HIV-infected patients on cART treated for DLBCL with CHOP between 2002-2010 in three academic hospitals. RESULTS: A total of 34 patients were included with 65% and 35% of patients receiving a PI and non-PI-based cART, respectively. Baseline characteristics between groups were similar; overall 85% were male, median age was 43 years, 50% had an International Prognostic Index (IPI) of 2-3 and median CD4(+) T-cell count was 225 cells/mm(3). CR was achieved in 77% and 58% of patients in the PI and non-PI groups, respectively (P=0.21), with 65% and 63% of patients achieving 2-year overall survival (P=1.00). A multivariate analysis showed that lower IPI score alone was significantly associated with higher CR rates (P=0.05). Toxicity was similar between both groups. CONCLUSIONS: Similar efficacy and toxicity of CHOP was observed in patients receiving a PI and non-PI-based cART.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções por HIV/complicações , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêuticoRESUMO
PURPOSE: Bortezomib has demonstrated promising activity in patients with follicular lymphoma (FL). This is the first study to evaluate the safety and efficacy of bortezomib added to rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) in previously untreated advanced-stage FL. PATIENTS AND METHODS: This is a phase II multicenter trial adding bortezomib (1.3 mg/m(2) days 1 and 8) to standard-dose R-CVP (BR-CVP) for up to eight cycles in patients with newly diagnosed stage III/IV FL requiring therapy. Two co-primary end points, complete response rate (complete response [CR]/CR unconfirmed [CRu]) and incidence of grade 3 or 4 neurotoxicity, were assessed. RESULTS: Between December 2006 and March 2009, 94 patients were treated with BR-CVP. Median patient age was 57 years (range, 29 to 84 years), and the majority had a high (47%) or intermediate (43%) Follicular Lymphoma International Prognostic Index score. BR-CVP was extremely well tolerated, with 90% of patients completing the intended eight cycles. No patients developed grade 4 neurotoxicity, and only five of 94 patients (5%; 95% CI, 0.8% to 9.9%) developed grade 3 neurotoxicity, which was largely reversible. On the basis of an intention-to-treat analysis, 46 of 94 patients (49%; 95% CI, 38.8% to 59.0%) achieved a CR/CRu, and 32 of 94 patients (34%) achieved a partial response, for an overall response rate of 83% (95% CI, 75.4% to 90.6%). CONCLUSION: The addition of bortezomib to standard-dose R-CVP for advanced-stage FL is feasible and well tolerated with minimal additional toxicity. The complete response rate in this high-risk population compares favorably to historical results of patients receiving R-CVP. Given these results, a phase III trial comparing BR-CVP with R-CVP is planned.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Ácidos Borônicos/administração & dosagem , Bortezomib , Canadá , Ciclofosfamida/administração & dosagem , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Pirazinas/administração & dosagem , Indução de Remissão , Rituximab , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
Ethylmalonic encephalopathy is a recently described inborn error of metabolism characterized clinically by developmental delay and regression, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhea. We describe monochorionic twins presenting with hypotonia in infancy and diagnosed with ethylmalonic encephalopathy on the basis of biochemical findings. They are compound heterozygote for missense mutations in ETHE1. Magnetic resonance imaging changes affecting the white matter, corpus callosum, and basal ganglia were seen in both patients. At 10 years of age, they have severe axial hypotonia but never displayed petechiae, orthostatic acrocyanosis, or chronic diarrhea. Their clinical courses differ markedly; one had an episode of coma when she was 3 years old and now has spastic quadraparesis and cannot speak. The other can freely use her upper extremities, her pyramidal syndrome being mostly limited to the lower extremities, and can speak 2 languages. These patients illustrate the clinical heterogeneity of ethylmalonic encephalopathy, even in monochorionic twins.