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1.
Lancet Haematol ; 8(4): e278-e288, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33770483

RESUMO

BACKGROUND: To improve the long-term tumour control in early, unfavourable Hodgkin Lymphoma, the German Hodgkin Study Group (GHSG) HD14 trial compared four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with an intensified chemotherapy regimen consisting of two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (escalated BEACOPP) plus two cycles of ABVD. The final analysis of the trial showed a significant advantage in terms of freedom from treatment failure (difference 7·2% [95% CI 3·8-10·5] at 5 years) for patients who received two cycles of escalated BEACOPP and two cycles of ABVD. However, there was no difference in overall survival between the two groups. To evaluate long-term efficacy and toxicity of this strategy, we did a follow-up analysis. METHODS: Patients aged 18-60 years with performance status of 2 or less and primary diagnosis of early, unfavourable Hodgkin lymphoma (all histologies) were included in an international, randomised, open-label, phase 3 trial. Patients were randomly assigned to receive four cycles of ABVD (ABVD group) or two cycles of escalated BEACOPP and two cycles of ABVD (2 + 2 group), both groups also received 30 Gy involved field radiotherapy. The ABVD dosing regimen was doxorubicin 25 mg/m2 (days 1 and 15), bleomycin 10 mg/m2 (days 1 and 15), vinblastine 6 mg/m2 (days 1 and 15), and dacarbazine 375 mg/m2 (days 1 and 15), repeated on day 29. The escalated BEACOPP dosing regimen was cyclophosphamide 1250 mg/m2 (day 1), doxorubicin 35 mg/m2 (day 1), etoposide 200 mg/m2 (days 1-3), procarbazine 100 mg/m2 (days 1-7), prednisone 40 mg/m2 (days 1-14), vincristine 1·4 mg/m2 (day 8; maximum 2 mg), and bleomycin 10 mg/m2 (day 8), repeated on day 22. After closure of the ABVD group according to prespecified rules, patients were assigned to receive two cycles of escalated BEACOPP and two cycles of ABVD (non-randomised 2 + 2 group), which continued until the end of the predefined 5-year recruitment period. In this prespecified long-term follow-up analysis, we aimed to evaluate the secondary endpoints progression-free survival, overall survival, and long-term toxicity. To this end, we did a descriptive intention-to-treat analysis of all qualified HD14 patients and on the predefined subsets of randomised qualified HD14 patients and patients in the non-randomised 2 + 2 group. The trial was registered on the International Standard Randomised Controlled Trial database, 04761296. FINDINGS: Between Jan 28, 2003, and Dec 29, 2009, 1686 patients were randomly assigned to the ABVD group (847 [50·2%] patients) and the 2 + 2 group (839 [49·8%] patients). 370 additional patients were recruited to the non-randomised 2 + 2 group. 1550 (92%) randomly assigned patients (median observation time 112 months [IQR 80-132]) and 339 (92%) patients in the non-randomised 2 + 2 group (median observation time 74 months [58-100]) were included in the qualified analysis set. 10-year overall survival in the randomly assigned patients was 94·1% (95% CI 92·0-95·7) for the ABVD group and 94·1% (91·8-95·7) for the 2 + 2 group (HR 1·0 [95% CI 0·6-1·5]; p=0·88). 8-year overall survival in the non-randomised 2 + 2 group was 95·1% (95% CI 91·6-97·2). 10-year progression-free survival in the randomly assigned patients was 85·6% (95% CI 82·6-88·1) for the ABVD group and 91·2% (88·4-93·3) for the 2 + 2 group (HR 0·5% [95% CI 0·4-0·7]; p=0·0001), accounting for a significant difference of 5·6% (95% CI 1·9-9·2) favouring the 2 + 2 group (p=0·0001). In the non-randomised 2 + 2 group, 8-year progression-free survival was 94·5% (95% CI 91·1-96·6). Standardised incidence ratios of second primary malignancies were similar between the ABVD group (2·3 [95% CI 1·6-3·1]) and the 2 + 2 group (2·5 [1·8-3·4]; Gray's p=0·80). Standardised incidence ratio of second primary malignancies was 3·1 (95% CI 1·7-5·0) in the non-randomised 2 + 2 group. INTERPRETATION: This long-term analysis confirms superior tumour control in the 2 + 2 group compared with the ABVD group without translating into an overall survival difference. At longer follow-up, there is no difference regarding second primary malignancies between groups. In conclusion, the 2 + 2 regimen spares a significant number of patients from the burden of relapse and additional treatment without increased long-term toxicity. FUNDING: Deutsche Krebshilfe eV and Swiss Federal Government.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adulto , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Feminino , Seguimentos , Alemanha/epidemiologia , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Segunda Neoplasia Primária/epidemiologia , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Procarbazina/administração & dosagem , Procarbazina/uso terapêutico , Intervalo Livre de Progressão , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Vincristina/administração & dosagem , Vincristina/uso terapêutico
2.
Rev. cuba. med ; 59(4): e1577, oct.-dic. 2020. tab, graf
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1144505

RESUMO

Introducción: El derrame pleural recidivante maligno se reproduce en breve tiempo y requiere el diagnóstico etiológico positivo de malignidad, la etiología más frecuente es el cáncer de pulmón. La pleurodesis química es el tratamiento de elección con la aplicación intrapleural de sustancias sinfisiantes. Objetivo: Describir la respuesta clínica y radiológica de los enfermos con derrame pleural recidivante maligno con el uso de bleomicina. Método: Estudio observacional comparativo en 30 pacientes con derrame pleural recidivante maligno divididos en dos grupos, en uno se aplicó la bleomicina intrapleural y al otro yodo povidona. Resultado: El 33,3 por ciento fueron del sexo masculino, 60 por ciento perteneció al grupo de edades de 60-69 años. El grupo tratado con bleomicina presentó una respuesta clínica favorable en los síntomas, p<0,005 después de la pleurodesis. En la evaluación de la respuesta radiológica, 66,6 por ciento pacientes tratados con la bleomicina tuvieron una resolución completa. Conclusiones: Se logró una buena respuesta clínica-radiológica con la pleurodesis química similar entre ambas modalidades de tratamiento. Se obtuvieron mejores resultados y menos reacciones adversas con la bleomicina intrapleural(AU)


Introduction: The malignant recurrent pleural effusion reproduces in short time and it requires a positive etiological diagnosis of malignancy, the most frequent etiology is lung cancer. Chemical pleurodesis is the treatment of choice with the intrapleural application of symphysiating substances. Objective: To describe the clinical and radiological response of patients with malignant recurrent pleural effusion with the use of bleomycin. Method: A comparative observational study in 30 patients with recurrent malignant pleural effusion was carried out. They were divided into two groups, one used intrapleural bleomycin and the other group used povidone iodine. Result: 33.3 percent were male, 60 percent belonged to the 60-69 age group. The group treated with bleomycin presented favorable clinical response in symptoms, p <0.005 after pleurodesis. At the evaluation of the radiological response, 66.6 percent patients treated with bleomycin had a complete resolution. Conclusions: Good clinical-radiological response was achieved with similar chemical pleurodesis between both treatment modalities. Better results and fewer adverse reactions were obtained with intrapleural bleomycin(AU)


Assuntos
Humanos , Masculino , Feminino , Bleomicina/uso terapêutico , Derrame Pleural Maligno/tratamento farmacológico
3.
Medicine (Baltimore) ; 99(38): e22297, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957389

RESUMO

RATIONALE: Growing teratoma syndrome is defined as an increase in tumor size during or after systemic chemotherapy for germ cell tumors. These cases involve normal tumor maker levels and histological features of only mature teratoma. We report a rare case of an ovarian immature teratoma in a Japanese child that was diagnosed as growing teratoma syndrome. PATIENT CONCERNS: A 12-year-old girl presented a painful abdominal mass. She underwent left salpingo-oophorectomy for grade 1 immature teratoma in the left ovary. She did not undergo additional chemotherapy or radiotherapy. Four months later, she presented with grade 3 immature teratoma disseminated into the abdomen and pelvis. Chemotherapy resulted in the tumor maker levels returning to their normal ranges, although the tumors had grown slightly. DIAGNOSIS: The specimens resected by laparotomy after the chemotherapy consisted of mature tissue predominantly, although primitive neuroepithelium was observed in a small part of the specimen. The pathological diagnosis was grade 1 immature teratoma, notwithstanding the clinical diagnosis was growing teratoma syndrome based on the clinical features and pathogenesis. INTERVENTIONS: Laparotomy was performed at 7 months after the first operation, with resection of various tumors as well as the rectum, sigmoid colon, residual left fallopian duct, and a small part of the ileum and omentum. Some small tumors at the parietal peritoneum were ablated, although many tiny tumors around the uterus were left untreated. OUTCOMES: The patient has been free from recurrence for 5 years. LESSONS: Growing teratoma syndrome can develop in children, and their tumor size is comparable to that in adolescents and adults. Furthermore, development of growing teratoma syndrome from a primary germ cell tumor is presumably faster in children than in adolescents and adults. Complete resection of all growing teratoma tissue is recommended, although fertility-sparing surgery should be considered when possible.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/terapia , Salpingo-Ooforectomia/métodos , Teratoma/terapia , Bleomicina/uso terapêutico , Criança , Cisplatino/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Humanos , Gradação de Tumores , Recidiva Local de Neoplasia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Síndrome , Teratoma/diagnóstico por imagem , Teratoma/patologia
4.
Ann Hematol ; 99(7): 1575-1581, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32500223

RESUMO

This study investigated the clinical characteristics of Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis (HLH-HL). Clinical data of 8 patients with HLH-HL and 20 non-HLH-HL patients were included. All eight HLH-HL patients tested positive for plasma Epstein-Barr virus (EBV)-DNA and EBV-encoded small RNA (EBER), and six patients were positive for EBV-DNA in the peripheral blood mononuclear cells (PBMCs). Two out of the 20 non-HLH-HL patients were confirmed positive for EBER, and the remaining 18 patients were negative. Among the HLH-HL patients, five patients received ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) chemotherapy regimens in other hospitals, and their conditions were considered to be worse, for which reason they were transferred to our center, and three patients were treated with DEP (doxorubicin-etoposide-methylprednisolone) regimens to target HLH and were alive as of the writing of this article. Two patients were critically ill upon admission and were not able to undergo chemotherapy. Significant differences in survival time were observed between the HLH-HL and non-HLH-HL patients (P = 0.005). HL patients found positive for EBV (plasma/PBMCs EBV-DNA(+)/EBER(+)) may be more likely to develop HLH-HL. It may be beneficial to target HLH during the acute phase of HLH, followed by treating HL once the HLH condition has stabilized. HLH-HL patients have worse prognosis and higher mortality than non-HLH-HL patients.


Assuntos
Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Estudos de Casos e Controles , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Etoposídeo/uso terapêutico , Feminino , Herpesvirus Humano 4/isolamento & purificação , Doença de Hodgkin/sangue , Doença de Hodgkin/complicações , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/complicações , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vimblastina/uso terapêutico , Adulto Jovem
5.
Medicine (Baltimore) ; 99(21): e20048, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481271

RESUMO

RATIONALE: Ustekinumab is a biological agent that inhibits interleukin 12 and 23 and has been approved for the treatment of moderate and severe plaque psoriasis. There have been case reports that raise concerns about its oncogenic potential. We are the first authors to report a case of Hodgkin lymphoma in a psoriatic patient receiving ustekinumab. PATIENT CONCERNS: A 22-year-old asymptomatic female patient presented to our department to investigate an enlarged cervical lymph node. Her past history was unremarkable, except for psoriasis since age 13. Two months before presentation the decision to administer Ustekinumab was taken and the patient had already received 3 doses. DIAGNOSES: During workup a Stage IV Hodgkin lymphoma was discovered. INTERVENTIONS: Ustekinumab administration was discontinued. The patient received treatment with the ABVD regimen. OUTCOMES: The patient's disease was refractory to the above-mentioned treatment. Therefore, a more aggressive regimen (BEACOPP escalated) was administered. LESSONS: Growing postmarketing surveillance data and case reports indicate that further research is warranted in order to elucidate a potential association between Ustekinumab and malignancy.


Assuntos
Fármacos Dermatológicos/efeitos adversos , Doença de Hodgkin/induzido quimicamente , Psoríase/tratamento farmacológico , Ustekinumab/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Prednisona/uso terapêutico , Procarbazina/uso terapêutico , Ustekinumab/administração & dosagem , Vincristina/uso terapêutico , Adulto Jovem
6.
J Vis Exp ; (158)2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32421010

RESUMO

Electrochemotherapy (ECT) is the combination of transient pore formation following electric pulse application with the administration of cytotoxic drugs, which enhances the cytotoxic effect of the applied agent due to membrane changes. In vitro 3D culture systems simulate the in vivo tumor growth and preserve the biological characteristics of tumors more accurately than conventional monolayer cell cultures. We describe a protocol for the development of 3D tumor organoids using conjunctival melanoma (CM) and uveal melanoma (UM) cell lines as well as the use of hand-held customized electrodes, suitable for in vitro ECT in the culture well without destruction of the tumor environment. This protocol analyzes the culture and growth of 3D CM and UM spheroids and their reaction to bleomycin (2.5 µg/mL) alone, electroporation (EP) (750 Volts/cm, 8 pulses, 100 µs, 5 Hz) alone, and ECT as a combination of EP and bleomycin. The drug concentration and the EP settings used in this protocol were established as preferred ECT conditions according to previous experiments. The assay used to determine the spheroid viability was conducted 3-7 days following treatment. The effect on viability and growth of the 3D tumor spheroids was significant only after ECT. The customized electrodes are described in detail in order to facilitate the application of pulses in the culture well. This novel treatment of 3D UM and CM spheroids sets a steppingstone for future clinical application.


Assuntos
Eletroquimioterapia/instrumentação , Eletroquimioterapia/métodos , Neoplasias Oculares/tratamento farmacológico , Melanoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Linhagem Celular Tumoral , Eletrodos , Eletroporação , Neoplasias Oculares/patologia , Humanos , Melanoma/patologia , Esferoides Celulares/efeitos dos fármacos
7.
Cochrane Database Syst Rev ; 4: CD010529, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32315458

RESUMO

BACKGROUND: Malignant pleural effusion (MPE) is a common problem for people with cancer and usually associated with considerable breathlessness. A number of treatment options are available to manage the uncontrolled accumulation of pleural fluid, including administration of a pleurodesis agent (via a chest tube or thoracoscopy) or placement of an indwelling pleural catheter (IPC). This is an update of a review published in Issue 5, 2016, which replaced the original, published in 2004. OBJECTIVES: To ascertain the optimal management strategy for adults with malignant pleural effusion in terms of pleurodesis success and to quantify differences in patient-reported outcomes and adverse effects between interventions. SEARCH METHODS: We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid) and three other databases to June 2019. We screened reference lists from other relevant publications and searched trial registries. SELECTION CRITERIA: We included randomised controlled trials of intrapleural interventions for adults with symptomatic MPE, comparing types of sclerosant, mode of administration and IPC use. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data on study design, characteristics, outcome measures, potential effect modifiers and risk of bias. The primary outcome was pleurodesis failure rate. Secondary outcomes were adverse events, patient-reported breathlessness control, quality of life, cost, mortality, survival, duration of inpatient stay and patient acceptability. We performed network meta-analyses of primary outcome data and secondary outcomes with enough data. We also performed pair-wise meta-analyses of direct comparison data. If we deemed interventions not jointly randomisable, or we found insufficient available data, we reported results by narrative synthesis. For the primary outcome, we performed sensitivity analyses to explore potential causes of heterogeneity and to evaluate pleurodesis agents administered via a chest tube only. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We identified 80 randomised trials (18 new), including 5507 participants. We found all except three studies at high or unclear risk of bias for at least one domain. Due to the nature of the interventions, most studies were unblinded. Pleurodesis failure rate We included 55 studies of 21 interventions in the primary network meta-analysis. We estimated the rank of each intervention's effectiveness. Talc slurry (ranked 6, 95% credible interval (Cr-I) 3 to 10)  is an effective pleurodesis agent (moderate certainty for comparison with placebo) and may result in fewer pleurodesis failures than bleomycin and doxycycline (bleomycin versus talc slurry: odds ratio (OR) 2.24, 95% Cr-I 1.10 to 4.68; low certainty; ranked 11, 95% Cr-I 7 to 15; doxycycline versus talc slurry: OR 2.51, 95% Cr-I 0.81 to 8.40; low certainty; ranked 12, 95% Cr-I 5 to 18). There is little evidence of a difference between the pleurodesis failure rate of talc poudrage and talc slurry (OR 0.50, 95% Cr-I 0.21 to 1.02; moderate certainty). Evidence for any difference was further reduced when restricting analysis to studies at low risk of bias (defined as maximum one high risk domain in the risk of bias assessment) (pleurodesis failure talc poudrage versus talc slurry: OR 0.78, 95% Cr-I 0.16 to 2.08). IPCs without daily drainage are probably less effective at obtaining a definitive pleurodesis (cessation of pleural fluid drainage facilitating IPC removal) than talc slurry (OR 7.60, 95% Cr-I 2.96 to 20.47; rank = 18/21, 95% Cr-I 13 to 21; moderate certainty). Daily IPC drainage or instillation of talc slurry via IPC are likely to reduce pleurodesis failure rates. Adverse effects Adverse effects were inconsistently reported. We performed network meta-analyses for the risk of procedure-related fever and pain. The evidence for risk of developing fever was of low certainty, but suggested there may be little difference between interventions relative to talc slurry (talc poudrage: OR 0.89, 95% Cr-I 0.11 to 6.67; bleomycin: OR 2.33, 95% Cr-I 0.45 to 12.50; IPCs: OR 0.41, 95% Cr-I 0.00 to 50.00; doxycycline: OR 0.85, 95% Cr-I 0.05 to 14.29). Evidence also suggested there may be little difference between interventions in the risk of developing procedure-related pain, relative to talc slurry (talc poudrage: OR 1.26, 95% Cr-I 0.45 to 6.04; very-low certainty; bleomycin: OR 2.85, 95% Cr-I 0.78 to 11.53; low certainty; IPCs: OR 1.30, 95% Cr-I 0.29 to 5.87; low certainty; doxycycline: OR 3.35, 95% Cr-I 0.64 to 19.72; low certainty). Patient-reported control of breathlessness Pair-wise meta-analysis suggests there is likely no difference in breathlessness control, relative to talc slurry, of talc poudrage ((mean difference (MD) 4.00 mm, 95% CI -6.26 to 14.26) on a 100 mm visual analogue scale for breathlessness; studies = 1; participants = 184; moderate certainty) and IPCs without daily drainage (MD -6.12 mm, 95% CI -16.32 to 4.08; studies = 2; participants = 160; low certainty). Overall mortality There may be little difference between interventions when compared to talc slurry (bleomycin and IPC without daily drainage; low certainty) but evidence is uncertain for talc poudrage and doxycycline. Patient acceptability Pair-wise meta-analysis demonstrated that IPCs probably result in a reduced risk of requiring a repeat invasive pleural intervention (OR 0.25, 95% Cr-I 0.13 to 0.48; moderate certainty) relative to talc slurry. There is likely little difference in the risk of repeat invasive pleural intervention with talc poudrage relative to talc slurry (OR 0.96, 95% CI 0.59 to 1.56; moderate certainty). AUTHORS' CONCLUSIONS: Based on the available evidence, talc poudrage and talc slurry are effective methods for achieving a pleurodesis, with lower failure rates than a number of other commonly used interventions. IPCs provide an alternative approach; whilst associated with inferior definitive pleurodesis rates, comparable control of breathlessness can probably be achieved, with a lower risk of requiring repeat invasive pleural intervention.  Local availability, global experience of agents and adverse events (which may not be identified in randomised trials) and patient preference must be considered when selecting an intervention. Further research is required to delineate the roles of different treatments according to patient characteristics, such as presence of trapped lung. Greater attention to patient-centred outcomes, including breathlessness, quality of life and patient preference is essential to inform clinical decision-making. Careful consideration to minimise the risk of bias and standardise outcome measures is essential for future trial design.


Assuntos
Metanálise em Rede , Derrame Pleural Maligno/terapia , Pleurodese/métodos , Adulto , Bleomicina/uso terapêutico , Doxiciclina/uso terapêutico , Dispneia/terapia , Febre/etiologia , Humanos , Iodo/uso terapêutico , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/mortalidade , Pleurodese/mortalidade , Quinacrina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Talco/uso terapêutico , Falha de Tratamento
8.
Leuk Res ; 91: 106336, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32151888

RESUMO

The 2017 WHO classification includes a new provisional entity of indolent T-lymphoproliferative disorders of the gastrointestinal tract (ITLPD-GIT). We investigated GI involvement of peripheral T-cell lymphoma (PTCL). Eighty-two patients were diagnosed with PTCL during 2007-2017. Eleven patients (13 %) had histologically-confirmed GI tract involvement {3 monomorphic epitheliotropic intestinal lymphoma (MEITL), 3 extranodal NK-/T-cell lymphoma nasal type (ENKL), 2 PTCL, not otherwise specified, 1 adult T-cell leukemia-lymphoma, 2 ITLPD-GIT}. Three patients each had lesions in the small intestine and multiple lesions, two each in the stomach and colon, and one in the duodenum. Six of the 11 patients remained alive. No perforation/stenosis was observed after chemo-radiotherapy, although one patient with ENKL developed gastric bleeding during chemotherapy. One patient with ITLPD-GIT (CD4-/CD8+/Ki67Low) with a colonic lesion showing diffuse edema and multiple aphtha by endoscope and diarrhea, initially diagnosed with MEITL, had active but stable disease after various chemotherapies for 1 year and no therapy for the next 5 years. Another patient with ITLPD-GIT (CD4+/CD8+/Ki67Low) with a localized gastric lesion and slight epigastralgia was in remission for 1 year after radiation. In conclusion, about 10 % of PTCLs were complicated by GI tract lesions and most had a poor prognosis. ITLPD-GIT should be considered as a differential diagnosis based on histology and clinical course. Local complications after chemo/radiotherapy in PTCL with GI involvement were not frequent.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Raios gama/uso terapêutico , Gastroenteropatias/terapia , Linfoma Extranodal de Células T-NK/terapia , Linfoma de Células T Periférico/terapia , Adulto , Idoso , Bleomicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Diagnóstico Diferencial , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/mortalidade , Gastroenteropatias/patologia , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/patologia , Trato Gastrointestinal/efeitos da radiação , Humanos , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/patologia , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/patologia , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Prednisona/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêutico
11.
Cardiovasc Intervent Radiol ; 43(4): 648-651, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32002622

RESUMO

Although there has been increased utilization of bleomycin in the treatment of low-flow vascular malformations in children, previous studies report minor adverse effects limited to skin changes/necrosis and flu-like symptoms (Horbach et al. in J Plast Reconstr Aesthet Surg 69(3):295-304, 2016). However, there have been rare reported cases of pulmonary injury observed in children after bleomycin intralesional administration. We report a case of fatal lung toxicity in a 15-month-old girl after injecting 7 units of bleomycin into a left cheek macrocystic lymphatic malformation. 1 week after therapy, she developed respiratory distress with imaging findings of pneumothorax and diffuse alveolar damage. Despite extensive management and resuscitative efforts of presumed pneumonitis, further decline resulted in death via respiratory failure. Early detection of pulmonary toxicity would allow prompt therapy and could avoid significant pulmonary damage.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Bleomicina/efeitos adversos , Pulmão/efeitos dos fármacos , Anormalidades Linfáticas/terapia , Escleroterapia/efeitos adversos , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/uso terapêutico , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Evolução Fatal , Feminino , Humanos , Lactente , Injeções Intralesionais , Resultado do Tratamento
12.
J Craniofac Surg ; 31(3): e250-e251, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31977688

RESUMO

Although surgical operation is a commonly preferred method in lymphangiomas (LAs), there is a risk of vascular or nerve injury especially in macrocystic LA. Therefore, sclerotherapy would be more appropriate as the first treatment. The authors wanted to share the excellent results of intralesional bleomycin treatment in 3 patients with cervical macrocystic LA.


Assuntos
Bleomicina/uso terapêutico , Linfangioma/tratamento farmacológico , Bleomicina/administração & dosagem , Pré-Escolar , Humanos , Lactente , Linfangioma/diagnóstico por imagem , Imagem por Ressonância Magnética , Escleroterapia , Resultado do Tratamento
13.
Hematol Oncol ; 38(2): 153-161, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31953864

RESUMO

The clinical management of older adult patients with Hodgkin lymphoma (HL) remains a major challenge. The aim of this study was to evaluate the impact of comorbidity assessment according to a standardized approach, the Cumulative Illness Rating Scale (CIRS), on prognosis in patients with classical HL aged 60 years and older. We studied 76 consecutive older adult patients with HL (median age 69 y, range 60-84) who had been treated in our institution between 1999 and 2018. Comorbidity was assessed at diagnosis according to CIRS. Anthracycline-containing chemotherapy with curative intent was administered in 59 (78%) patients. We identified 41 (54%) patients with at least one severe comorbidity rated on CIRS grade ≥ 3. Patients with severe comorbidity were more likely to have advanced-stage disease (P = .003), to have an International Prognostic Score (IPS) > 3 (P = .03), and to not receive anthracycline-containing chemotherapy (P = .008). The probability of overall survival (OS) at 3 years was 88% (95% CI, 71%-95%) in patients without severe comorbidities, while it was only 46% (95% CI, 29%-62%) in patients with a comorbidity CIRS grade ≥ 3 (P = .0001). The impact of comorbidity on prognosis was also evident when restricting the analysis to patients treated with anthracycline-containing therapy. The 3-year OS was 93% (95% CI, 76%-98%) (P = .004) in patients without severe comorbidity and 72% (95% CI, 47%-87%) in patients with severe comorbidity (P = .004). In a multivariate analysis, presence of comorbidity, but not age, was a significant factor for OS. Therefore, we conclude that a significant proportion of older adult patients with HL has severe comorbidity on the CIRS scale, which impacts more importantly than age on prognosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/patologia , Idoso , Idoso de 80 Anos ou mais , Bleomicina/uso terapêutico , Comorbidade , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Doença de Hodgkin/tratamento farmacológico , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Vimblastina/uso terapêutico
14.
Blood ; 135(10): 735-742, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-31945149

RESUMO

The phase 3 ECHELON-1 study demonstrated that brentuximab vedotin (A) with doxorubicin, vinblastine, and dacarbazine (AVD; A+AVD) exhibited superior modified progression-free survival (PFS) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for frontline treatment of patients with stage III/IV classical Hodgkin lymphoma (cHL). Maturing positron emission tomography (PET)-adapted trial data highlight potential limitations of PET-adapted approaches, including toxicities with dose intensification and higher-than-expected relapse rates in PET scan after cycle 2 (PET2)-negative (PET2-) patients. We present an update of the ECHELON-1 study, including an exploratory analysis of 3-year PFS per investigator. A total of 1334 patients with stage III or IV cHL were randomized 1:1 to receive 6 cycles of A+AVD (n = 664) or ABVD (n = 670). Interim PET2 was required. At median follow-up of 37 months, 3-year PFS rates were 83.1% with A+AVD and 76.0% with ABVD; 3-year PFS rates in PET2- patients aged <60 years were 87.2% vs 81.0%, respectively. A beneficial trend in PET2+ patients aged <60 years on A+AVD was also observed, with a 3-year PFS rate of 69.2% vs 54.7% with ABVD. The benefit of A+AVD in the intent-to-treat population appeared independent of disease stage and prognostic risk factors. Upon continued follow-up, 78% of patients with peripheral neuropathy on A+AVD had either complete resolution or improvement compared with 83% on ABVD. These data highlight that A+AVD provides a durable efficacy benefit compared with ABVD for frontline stage III/IV cHL, consistent across key subgroups regardless of patient status at PET2, without need for treatment intensification or bleomycin exposure. This trial was registered at www.clinicaltrials.gov as #NCT01712490 (EudraCT no. 2011-005450-60).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brentuximab Vedotin/administração & dosagem , Doença de Hodgkin/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bleomicina/uso terapêutico , Brentuximab Vedotin/efeitos adversos , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico
15.
Am J Physiol Lung Cell Mol Physiol ; 318(2): L376-L385, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31851533

RESUMO

The systemic delivery of bleomycin (BLM) to mice through subcutaneously implanted osmotic minipumps may be used to experimentally mimic the typical features of systemic sclerosis and related interstitial lung diseases. The published studies on this model principally have focused on induced dermal modifications, probably because lung lesions are typically mild, subpleurally localized, and difficult to analyze. The use of high BLM doses to increase their severity has been proposed but is ethically questionable because of the compromising of animal welfare. We propose a tailored histomorphometric method suitable to detect and quantify this type of mild lung lesions. Using a two-step automated image analysis, a peripheral region of interest with a depth of 250 µm from the pleural edge was defined on whole slide images, and the fibrotic foci were histomorphometrically characterized. The effects of different BLM doses on lung alterations were evaluated in C57BL/6 mice and 60 U/kg resulted in a fair compromise between fibrotic lesions and animal welfare. This dose was also tested in time course experiments. The analysis revealed a peak of histological fibrotic-like alterations, cytokine expression, metalloprotease, and macrophagic activation between the 21st and 28th day after pump implant. The induced dermal fibrosis was characterized by the progressive loss of the white dermal adipose layer, an increase in dermal thickness, dermal hyperplasia, and more compacted collagen fibers. Despite the trend toward spontaneous resolution, our model allowed a double organ readout of the BLM effect and the identification of a therapeutic window for testing pharmacological compounds without using life-threatening doses.


Assuntos
Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Bombas de Infusão , Fibrose Pulmonar/tratamento farmacológico , Animais , Derme/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/patologia , Fatores de Tempo
16.
J Craniofac Surg ; 31(2): 372-376, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31764560

RESUMO

PURPOSE: Despite many advances in the knowledge of vascular malformations, extracranial arteriovenous malformations (AVMs) remain an enigma and are usually misdiagnosed and mismanaged due to their associated rare morbidity. This study aimed to describe the clinical course and emphasize the progressive nature of AVMs through a retrospective study of 446 patients. METHODS: Patients with cutaneous and soft-tissue AVMs presenting to our Vascular Anomalies Center between March 2011 and March 2017 were reviewed. Medical records were examined for disease course, age at first presentation at our institution, distributions and locations of lesions, clinical staging, progression, and previous treatments. Progression was defined as advancement to a higher Schobinger stage from a lower stage. RESULTS: A total of 446 patients (mean age, 25.6 ±â€Š14.0 years) were enrolled in this study, including 232 (52.0%) males (gender ratio, 1.08:1). Arteriovenous malformations lesions in 76.7% (342/446) of the patients were located in the head and neck. Children with Stage I AVMs had a 41.9% risk of progression before adolescence and an 80.0% risk of progression before adulthood. Nearly all patients (96.2%) showed progression in adulthood. Diffuse lesions were more likely to progress than localized lesions (P < 0.05) in childhood and adolescence. Lesions in the head and neck regions were less likely to progress than those in other regions in childhood (P = 0.005). A total of 216 (48.4%) patients had undergone previous treatments. Among these patients, bleomycin showed an unintentional positive effect in the treatment of AVMs. CONCLUSIONS: Extracranial AVMs have a continuously progressive nature. A full understanding regarding the progressive course of AVMs can lead patients and physicians to attach importance to early diagnosis and management. Meanwhile exploring innovative treatments should be focused in the future to prevent potential destructive progression.


Assuntos
Malformações Arteriovenosas/diagnóstico , Adolescente , Adulto , Malformações Arteriovenosas/terapia , Bleomicina/uso terapêutico , Criança , Terapia Combinada , Progressão da Doença , Feminino , Cabeça/irrigação sanguínea , Humanos , Masculino , Pescoço/irrigação sanguínea , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
J Nucl Med ; 61(1): 40-45, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31201248

RESUMO

We assessed the predictive value of new radiomic features characterizing lesion dissemination in baseline 18F-FDG PET and tested whether combining them with baseline metabolic tumor volume (MTV) could improve prediction of progression-free survival (PFS) and overall survival (OS) in diffuse large B-cell lymphoma (DLBCL) patients. Methods: From the LNH073B trial (NCT00498043), patients with advanced-stage DLCBL and 18F-FDG PET/CT images available for review were selected. MTV and several radiomic features, including the distance between the 2 lesions that were farthest apart (Dmaxpatient), were calculated. Receiver-operating-characteristic analysis was used to determine the optimal cutoff for quantitative variables, and Kaplan-Meier survival analyses were performed. Results: With a median age of 46 y, 95 patients were enrolled, half of them treated with R-CHOP biweekly (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and the other half with R-ACVBP (rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone), with no significant impact on outcome. Median MTV and Dmaxpatient were 375 cm3 and 45 cm, respectively. The median follow-up was 44 mo. High MTV and Dmaxpatient were adverse factors for PFS (P = 0.027 and P = 0.0003, respectively) and for OS (P = 0.0007 and P = 0.0095, respectively). In multivariate analysis, only Dmaxpatient was significantly associated with PFS (P = 0.0014) whereas both factors remained significant for OS (P = 0.037 and P = 0.0029, respectively). Combining MTV (>384 cm3) and Dmaxpatient (>58 cm) yielded 3 risk groups for PFS (P = 0.0003) and OS (P = 0.0011): high with 2 adverse factors (4-y PFS and OS of 50% and 53%, respectively, n = 18), low with no adverse factor (94% and 97%, n = 36), and an intermediate category with 1 adverse factor (73% and 88%, n = 41). Conclusion: Combining MTV with a parameter reflecting the tumor burden dissemination further improves DLBCL patient risk stratification at staging.


Assuntos
Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Feminino , Fluordesoxiglucose F18 , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Estadiamento de Neoplasias , Prednisona/uso terapêutico , Curva ROC , Medição de Risco , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico , Vindesina/uso terapêutico , Adulto Jovem
18.
Neoplasma ; 67(1): 203-208, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31829022

RESUMO

Few studies focused on the relationship between hepatitis B virus (HBV) infection and classical Hodgkin lymphoma (cHL). This study was to evaluate the impact of HBV infection on the treatment outcome and survival of cHL patients. Clinical data of 352 cHL patients treated with ABVD regimen (doxorubicin, bleomycin, vincristine and dacarbazine) between January 2002 and January 2018 were retrospectively collected. According to HBV infection status, the patients were divided into three groups: with HBV infection [hepatitis B surface antigen (HBsAg)-positive], with past HBV infection [HBsAg-negative but anti-hepatitis B core antigen (anti-HBc)-positive], and without HBV infection (HBsAg-negative and anti-HBc-negative). The incidence of HBV infection and past HBV infection in cHL patients were 7.4% (26/352) and 16.5% (58/352), respectively. The median age of patients without HBV infection was lower than those in other two groups (p<0.001). The complete remission rates after first-line therapy were different among 3 groups (65.4% for the group with HBV infection, 87.9% for the group with past HBV infection, and 76.1% for the group without HBV infection, respectively, p=0.049). After a median follow-up of 34.6 months, the 3-year progression-free survival rates for the three groups were 69%, 74% and 80%, respectively (p=0.566) and the 3-year overall survival rates were 72%, 91% and 87%, respectively (p=0.096). No HBV reactivation was observed during chemotherapy among 3 groups, but 1 patient in the group with HBV infection experienced delayed HBV reactivation when prophylactic entecavir was discontinued 12 months after the last cycle of chemotherapy. HBV infection status did not affect the clinical outcome and prognosis of cHL patients, especially in the era of prophylactic antiviral therapy.


Assuntos
Hepatite B/complicações , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/virologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Antígenos do Núcleo do Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Humanos , Prognóstico , Estudos Retrospectivos , Vimblastina/uso terapêutico
19.
J Dermatolog Treat ; 31(3): 235-240, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096794

RESUMO

Background: The aim of this study was to assess the efficacy of combination between microneedling with dermapen and topical bleomycin in the treatment of plantar warts in comparison with intralesional bleomycin and intralesional saline (placebo).Methods: Fifty-four patients were assigned into three groups, each containing 18 patients. The first group treated by micro-needling phenotype with topical bleomycin at 2 weeks interval, the second group received intralesional bleomycin at 3 weeks interval and the control group was intralesional saline for a maximum of four weeks.Results: Complete clearance of warts in 16 patients in the micro-needling group (88.9%) versus 15 patients (83.3%) in the intralesional bleomycin group versus one patient (5.6%) in the control group .Conclusions: Microneedling assisted topical bleomycin spraying seems to be a promising effective and noninvasive therapeutic modality for recalcitrant plantar warts that facilitates delivery and absorption of bleomycin into the lesion .


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Bleomicina/uso terapêutico , Doenças do Pé/terapia , Verrugas/terapia , Adolescente , Adulto , Crioterapia , Feminino , Doenças do Pé/tratamento farmacológico , Doenças do Pé/patologia , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Agulhas , Verrugas/tratamento farmacológico , Verrugas/patologia , Adulto Jovem
20.
J Glob Oncol ; 5: 1-13, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31834832

RESUMO

PURPOSE: Escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) improves overall survival (OS) in patients with Hodgkin lymphoma (HL) relative to ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) therapy. However, the associated higher cost and toxicity discourage clinicians from prescribing it. Identifying high-risk patients and administering escalated BEACOPP remains an effective strategy. We assessed the significance of interim positron emission tomography (iPET) scan after 2 cycles (iPET2) in identifying this high-risk subset. PATIENTS AND METHODS: This cohort study used secondary data from 12 tertiary care centers in South India gathered over 10 years (2008-2018). OS, event-free survival (EFS), determinants of EFS, and complete response (CR) in iPET2 were assessed. RESULTS: The study included 409 patients with HL (mean age, 34.5 years; male/female ratio, 1.4:1). The median duration of follow-up was 2.8 years. Of 409 patients, 63% underwent PET-based staging and 37% underwent computerized tomography (CT) staging. Stage IV (28.9%) and bone involvement (9.2%) were seen more often with PET than with CT staging (9.2% and 2%, respectively). Among 171 patients with iPET2 results, 24% did not achieve CR, and no factors were significantly associated. The 5-year EFS and OS rates of the entire cohort were 78% and 97%, respectively. The 5-year EFS and OS rates of patients with CR on iPET2 were 90% and 99%, respectively, whereas these were 65% and 100%, respectively, for patients not achieving CR. On univariable analysis, sex, stage, and iPET2 response significantly predicted inferior EFS. On multivariate analysis, only iPET2 response significantly predicted EFS (P < .000). CONCLUSION: Our study supports the use of PET for staging and iPET2 for response assessment. Nonachievement of CR on iPET2 indicates unfavorable outcome, and such patients may benefit from more intensive treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/efeitos adversos , Bleomicina/uso terapêutico , Criança , Pré-Escolar , Dacarbazina/efeitos adversos , Dacarbazina/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Índia , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Adulto Jovem
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