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1.
Pediatr Blood Cancer ; 68(8): e29126, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34019326

RESUMO

No guidelines exist for which intensive chemotherapy regimen is best in pediatric or young adult patients with high-risk posttransplant lymphoproliferative disorder (PTLD). We retrospectively reviewed patients with PTLD who received interval-compressed short-course etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (SC-EPOCH) regimens at our institution. Eight patients were included with median age of 12 years. All patients achieved a complete response with a manageable toxicity profile. Two patients developed second, clonally unrelated, EBV-positive PTLD and one patient had recurrence at 6 months off therapy. No graft rejection occurred during therapy. All eight patients are alive with median follow-up of 29 months.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transtornos Linfoproliferativos , Transplante de Órgãos/efeitos adversos , Criança , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Humanos , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/etiologia , Complicações Pós-Operatórias , Prednisona/uso terapêutico , Prognóstico , Estudos Retrospectivos , Vincristina/uso terapêutico , Adulto Jovem
2.
Pediatr Blood Cancer ; 65(1)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28792686

RESUMO

BACKGROUND: While viral surveillance of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus using PCR is routine in patients undergoing hematopoetic stem cell transplant and solid organ transplant, the utility in the nontransplant pediatric leukemia population is unknown. Our institution screens patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) for viral DNAemia by PCR as part of clinical care. PROCEDURE: This retrospective chart review included patients treated for newly diagnosed or relapsed AML or ALL between April 2010 and September 2014. We retrieved data for viral PCR screening, detection and quantification, duration of positivity, and prophylaxis or treatment. RESULTS: One hundred eleven patients were included in analyses. Forty (36.0%) had at least one blood PCR positive for EBV, CMV, or adenovirus. Patients with ALL had significantly higher rates of persistent viral detection and treatment than those with AML (P < 0.02, P < 0.01, respectively). International patients had significantly higher rates of viral detection (P < 0.01), persistence (P < 0.01), any treatment (P < 0.03), and antiviral treatment (P < 0.01); 16.9% of patients who received intravenous immunoglobulin (IVIG) prophylactically had viral detection compared to 63% of patients who did not receive prophylactic IVIG (P = 0.0008). CONCLUSIONS: Patients with ALL were more susceptible than those with AML to viral reactivation that was persistent or resulted in treatment. Patients with relapsed ALL, refractory ALL, or infantile ALL are most likely to benefit from asymptomatic screening for CMV and adenovirus. International patients are at higher risk for reactivation and may merit screening. EBV reactivation was not significant and does not warrant screening.


Assuntos
Infecções por Vírus de DNA/sangue , Vírus de DNA , DNA Viral/sangue , Leucemia Mieloide Aguda , Reação em Cadeia da Polimerase/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Infecções por Vírus de DNA/prevenção & controle , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Lactente , Recém-Nascido , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/virologia , Masculino
3.
Pediatr Blood Cancer ; 64(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28544595

RESUMO

Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of cellular and bispecific T-cell engaging immunotherapy. Checkpoint blockade using anti-programmed cell death 1 (anti-PD-1) inhibitors is an approach to antitumor immune system stimulation. A 29-year-old female with alveolar soft part sarcoma developed severe CRS after treatment with anti-PD-1 therapy. CRS was characterized by high fevers, encephalopathy, hypotension, hypoxia, hepatic dysfunction, and evidence of coagulopathy, and resolved after infusion of the interleukin-6 inhibitor tocilizumab and corticosteroids.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Citocinas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Sarcoma/tratamento farmacológico , Adulto , Feminino , Humanos , Neoplasias Pulmonares/complicações , Alvéolos Pulmonares , Sarcoma/complicações , Síndrome
4.
Biomaterials ; 51: 22-29, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25770994

RESUMO

Nanomedicine-based strategies have the potential to improve therapeutic performance of a wide range of anticancer agents. However, the successful implementation of nanoparticulate delivery systems requires the development of adequately sized nanocarriers delivering their therapeutic cargo to the target in a protected, pharmacologically active form. The present studies focused on a novel nanocarrier-based formulation strategy for SN-38, a topoisomerase I inhibitor with proven anticancer potential, whose clinical application is compromised by toxicity, poor stability and incompatibility with conventional delivery vehicles. SN-38 encapsulated in biodegradable sub-100 nm sized nanoparticles (NP) in the form of its rapidly activatable prodrug derivative with tocopherol succinate potently inhibited the growth of neuroblastoma cells in a dose- and exposure time-dependent manner, exhibiting a delayed response pattern distinct from that of free SN-38. In a xenograft model of neuroblastoma, prodrug-loaded NP caused rapid regression of established large tumors, significantly delayed tumor regrowth after treatment cessation and markedly extended animal survival. The NP formulation strategy enabled by a reversible chemical modification of the drug molecule offers a viable means for SN-38 delivery achieving sustained intratumoral drug levels and contributing to the potency and extended duration of antitumor activity, both prerequisites for effective treatment of neuroblastoma and other cancers.


Assuntos
Camptotecina/análogos & derivados , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Neuroblastoma/tratamento farmacológico , Pró-Fármacos/uso terapêutico , Animais , Camptotecina/administração & dosagem , Camptotecina/química , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Irinotecano , Camundongos Nus , Neuroblastoma/patologia , Tamanho da Partícula , Pró-Fármacos/administração & dosagem , Resultado do Tratamento , alfa-Tocoferol/química , alfa-Tocoferol/farmacologia , alfa-Tocoferol/uso terapêutico
5.
Cancer Lett ; 360(2): 205-12, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25684664

RESUMO

Neuroblastoma (NB) is the most common and deadly solid tumor in children. The majority of NB patients have advanced stage disease with poor prognosis, so more effective, less toxic therapy is needed. We developed a novel nanocarrier-based strategy for tumor-targeted delivery of a prodrug of SN38, the active metabolite of irinotecan. We formulated ultrasmall-sized (<100 nm) biodegradable poly(lactide)-poly(ethylene glycol) based nanoparticles (NPs) containing SN38 conjugated to tocopherol succinate (SN38-TS). Alternative dosing schedules of SN38-TS NPs were compared to irinotecan. Comparison of SN38-TS NPs (2 doses) with irinotecan (20 doses) showed equivalent efficacy but no cures. Comparison of SN38-TS NPs (8, 8, and 16 doses, respectively) to irinotecan (40 doses) showed that all SN38-TS NP regimens were far superior to irinotecan, and "cures" were obtained in all NP arms. SN38-TS NP delivery resulted in 200× the amount of SN38 in NB tumors at 4 hr post-treatment, compared to SN38 detected for the irinotecan arm; no toxicity was seen with NPs. We conclude that this SN38-TS NP formulation improved delivery, retention, and efficacy, without causing systemic toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/análogos & derivados , Nanopartículas/administração & dosagem , Neuroblastoma/tratamento farmacológico , Pró-Fármacos/administração & dosagem , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Camptotecina/administração & dosagem , Camptotecina/química , Camptotecina/farmacocinética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Irinotecano , Camundongos , Camundongos Nus , Nanopartículas/química , Neuroblastoma/metabolismo , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Pediatr Blood Cancer ; 59(2): 226-32, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21990266

RESUMO

BACKGROUND: Neuroblastomas (NBs) are characterized by clinical heterogeneity, from spontaneous regression to relentless progression. The pattern of NTRK family gene expression contributes to these disparate behaviors. TrkA/NTRK1 is expressed in favorable NBs that regress or differentiate, whereas TrkB/NTRK2 and its ligand brain-derived neurotrophic factor (BDNF) are co-expressed in unfavorable NBs, representing an autocrine survival pathway. We determined the significance of NTRK family gene expression in a large, representative set of primary NBs. PATIENTS AND METHODS: We analyzed the expression of the following genes in 814 NBs using quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR): NTRK1, NTRK2, NTRK3, P75/NGFR, nerve growth factor (NGF), BDNF, IGFR1, and EGFR. Expression (high vs. low) was dichotomized by median expression value and compared to clinical and biological variables as well as outcome. RESULTS: High NTRK1 expression was strongly correlated with favorable age, stage, MYCN status, histology, ploidy, risk group, and outcome (P < 0.0001 for all). However, it did not add significantly to the panel of prognostic variables currently used for cooperative group trials. NTRK2 expression was associated with risk factors but not with outcome. High NGF expression was also associated with most risk factors and weakly with unfavorable outcome. CONCLUSIONS: High expression of NTRK1 is strongly associated with favorable risk factors and outcome in a large, representative population of NB patients. It did not add significantly to the current risk prediction algorithm, but it may contribute to future expression classifiers. Indeed, prospective assessment of NTRK1 and NTRK2 expression will identify tumors that would be candidates for NTRK-targeted therapy, either alone or in combination with conventional agents.


Assuntos
Biomarcadores Tumorais/genética , Fatores de Crescimento Neural/genética , Neuroblastoma/genética , Proteínas Nucleares/genética , Proteínas Oncogênicas/genética , Receptor de Fator de Crescimento Neural/genética , Receptor trkA/genética , Biomarcadores Tumorais/metabolismo , Humanos , Lactente , Proteína Proto-Oncogênica N-Myc , Fatores de Crescimento Neural/metabolismo , Neuroblastoma/metabolismo , Neuroblastoma/mortalidade , Proteínas Nucleares/metabolismo , Proteínas Oncogênicas/metabolismo , Prognóstico , RNA Mensageiro/genética , Receptor de Fator de Crescimento Neural/metabolismo , Receptor trkA/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida
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