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1.
Blood ; 142(23): 1960-1971, 2023 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-37647654

RESUMO

Sorafenib maintenance improves outcomes after hematopoietic cell transplant (HCT) for patients with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML). Although promising outcomes have been reported for sorafenib plus intensive chemotherapy, randomized data are limited. This placebo-controlled, phase 2 study (ACTRN12611001112954) randomized 102 patients (aged 18-65 years) 2:1 to sorafenib vs placebo (days 4-10) combined with intensive induction: idarubicin 12 mg/m2 on days 1 to 3 plus either cytarabine 1.5 g/m2 twice daily on days 1, 3, 5, and 7 (18-55 years) or 100 mg/m2 on days 1 to 7 (56-65 years), followed by consolidation and maintenance therapy for 12 months (post-HCT excluded) in newly diagnosed patients with FLT3-ITD AML. Four patients were excluded in a modified intention-to-treat final analysis (3 not commencing therapy and 1 was FLT3-ITD negative). Rates of complete remission (CR)/CR with incomplete hematologic recovery were high in both arms (sorafenib, 78%/9%; placebo, 70%/24%). With 49.1-months median follow-up, the primary end point of event-free survival (EFS) was not improved by sorafenib (2-year EFS 47.9% vs 45.4%; hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.51-1.51; P = .61). Two-year overall survival (OS) was 67% in the sorafenib arm and 58% in the placebo arm (HR, 0.76; 95% CI, 0.42-1.39). For patients who received HCT in first remission, the 2-year OS rates were 84% and 67% in the sorafenib and placebo arms, respectively (HR, 0.45; 95% CI, 0.18-1.12; P = .08). In exploratory analyses, FLT3-ITD measurable residual disease (MRD) negative status (<0.001%) after induction was associated with improved 2-year OS (83% vs 60%; HR, 0.4; 95% CI, 0.17-0.93; P = .028). In conclusion, routine use of pretransplant sorafenib plus chemotherapy in unselected patients with FLT3-ITD AML is not supported by this study.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Sorafenibe , Tirosina Quinase 3 Semelhante a fms/genética , Estudos Retrospectivos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética
2.
Am J Hematol ; 99(7): 1281-1289, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38700035

RESUMO

The Phase 2 portion of this study evaluated safety and efficacy of polatuzumab vedotin 1.8 mg/kg and venetoclax 800 mg, plus fixed-dose obinutuzumab 1000 mg or rituximab 375 mg/m2 in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), respectively. Patients with complete response (CR) or partial response (PR)/stable disease (FL) or CR/PR (DLBCL) at end of induction (EOI; six 21-day cycles) received post-induction therapy with venetoclax and obinutuzumab or rituximab, respectively. Primary endpoint was CR rate at EOI. Safety-evaluable populations included 74 patients (FL cohort; median age 64 years; progression of disease within 24 months on first-line treatment, 25.7%; FL International Prognostic Index 3-5, 54.1%; ≥2 previous therapies, 74.3%) and 57 patients (DLBCL cohort; median age 65 years; International Prognostic Index 3-5, 54.4%; ≥2 previous therapies, 77.2%). The most common non-hematologic adverse events (mostly Grades 1-2) in the FL and DLBCL cohorts were diarrhea (55.4% and 47.4%, respectively) and nausea (47.3% and 36.8%); neutropenia was the most common Grades 3-4 toxicity (39.2% and 52.6%). Efficacy-evaluable populations included patients treated at the recommended Phase 2 dose (FL, n = 49; DLBCL, n = 48). CR rates at EOI were 59.2% (FL) and 31.3% (DLBCL); median progression-free survival was 22.8 months (95% confidence interval [CI], 14.5-not evaluable) and 4.6 months (95% CI, 3.6-8.1), respectively. Polatuzumab vedotin plus venetoclax and obinutuzumab/rituximab had acceptable safety in patients with R/R FL or DLBCL, with promising response rates in R/R FL, including high-risk patients.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Compostos Bicíclicos Heterocíclicos com Pontes , Linfoma Difuso de Grandes Células B , Rituximab , Sulfonamidas , Humanos , Pessoa de Meia-Idade , Idoso , Masculino , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Sulfonamidas/efeitos adversos , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Adulto , Idoso de 80 Anos ou mais , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Rituximab/efeitos adversos , Linfoma Folicular/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Recidiva , Imunoconjugados
3.
Am J Hematol ; 98(3): 449-463, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36594167

RESUMO

The treatment of patients with relapsed or refractory lymphoid neoplasms represents a significant clinical challenge. Here, we identify the pro-survival BCL-2 protein family member MCL-1 as a resistance factor for the BCL-2 inhibitor venetoclax in non-Hodgkin lymphoma (NHL) cell lines and primary NHL samples. Mechanistically, we show that the antibody-drug conjugate polatuzumab vedotin promotes MCL-1 degradation via the ubiquitin/proteasome system. This targeted MCL-1 antagonism, when combined with venetoclax and the anti-CD20 antibodies obinutuzumab or rituximab, results in tumor regressions in preclinical NHL models, which are sustained even off-treatment. In a Phase Ib clinical trial (NCT02611323) of heavily pre-treated patients with relapsed or refractory NHL, 25/33 (76%) patients with follicular lymphoma and 5/17 (29%) patients with diffuse large B-cell lymphoma achieved complete or partial responses with an acceptable safety profile when treated with the recommended Phase II dose of polatuzumab vedotin in combination with venetoclax and an anti-CD20 antibody.


Assuntos
Imunoconjugados , Linfoma não Hodgkin , Humanos , Proteína de Sequência 1 de Leucemia de Células Mieloides/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Rituximab/uso terapêutico , Imunoconjugados/uso terapêutico
4.
Blood ; 136(23): 2628-2637, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-32785666

RESUMO

This open-label phase 2 study (CONTRALTO) assessed the safety and efficacy of BCL-2 inhibitor venetoclax (VEN) plus rituximab (R), and VEN plus bendamustine (B) and R, vs B + R (BR) alone in relapsed/refractory (R/R) follicular lymphoma. Patients in the chemotherapy-free arm (arm A: VEN + R) received VEN 800 mg/d plus R 375 mg/m2 on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 4, 6, 8, 10, and 12. After a safety run-in with VEN 600 mg, patients in the chemotherapy-containing cohort were randomized to either VEN + BR (arm B; VEN 800 mg/d for 1 year + 6 cycles of BR [B 90 mg/m2 on days 1 and 2 and R 375 mg/m2 on day 1]) or 6 cycles of BR (arm C). Overall, 163 patients were analyzed (9 in the safety run-in and 52, 51, and 51 in arms A, B, and C, respectively). Complete metabolic/complete response rates were 17% (arm A), 75% (arm B), and 69% (arm C). Of patients in arm B, only 61% received ≥90% of the planned B dose vs 96% of patients in arm C. More frequent hematologic toxicity resulted in more reduced dosing/treatment discontinuation in arm B vs arm C. Rates of grade 3/4 adverse events were 51.9%, 93.9%, and 60.0% in arms A, B, and C, respectively. VEN + BR led to increased toxicity and lower dose intensity of BR than in arm C, but efficacy was similar. Optimizing dose and schedule to maintain BR dose intensity may improve efficacy and tolerability of VEN + BR, while VEN + R data warrant further study. This study was registered at www.clinicaltrials.gov as #NCT02187861.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Folicular/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Feminino , Humanos , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos
5.
Lancet ; 393(10168): 229-240, 2019 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-30522922

RESUMO

BACKGROUND: Based on the encouraging activity and manageable safety profile observed in a phase 1 study, the ECHELON-2 trial was initiated to compare the efficacy and safety of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for the treatment of CD30-positive peripheral T-cell lymphomas. METHODS: ECHELON-2 is a double-blind, double-dummy, randomised, placebo-controlled, active-comparator phase 3 study. Eligible adults from 132 sites in 17 countries with previously untreated CD30-positive peripheral T-cell lymphomas (targeting 75% with systemic anaplastic large cell lymphoma) were randomly assigned 1:1 to receive either A+CHP or CHOP for six or eight 21-day cycles. Randomisation was stratified by histological subtype according to local pathology assessment and by international prognostic index score. All patients received cyclophosphamide 750 mg/m2 and doxorubicin 50 mg/m2 on day 1 of each cycle intravenously and prednisone 100 mg once daily on days 1 to 5 of each cycle orally, followed by either brentuximab vedotin 1·8 mg/kg and a placebo form of vincristine intravenously (A+CHP group) or vincristine 1·4 mg/m2 and a placebo form of brentuximab vedotin intravenously (CHOP group) on day 1 of each cycle. The primary endpoint, progression-free survival according to blinded independent central review, was analysed by intent-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01777152. FINDINGS: Between Jan 24, 2013, and Nov 7, 2016, 601 patients assessed for eligibility, of whom 452 patients were enrolled and 226 were randomly assigned to both the A+CHP group and the CHOP group. Median progression-free survival was 48·2 months (95% CI 35·2-not evaluable) in the A+CHP group and 20·8 months (12·7-47·6) in the CHOP group (hazard ratio 0·71 [95% CI 0·54-0·93], p=0·0110). Adverse events, including incidence and severity of febrile neutropenia (41 [18%] patients in the A+CHP group and 33 [15%] in the CHOP group) and peripheral neuropathy (117 [52%] in the A+CHP group and 124 [55%] in the CHOP group), were similar between groups. Fatal adverse events occurred in seven (3%) patients in the A+CHP group and nine (4%) in the CHOP group. INTERPRETATION: Front-line treatment with A+CHP is superior to CHOP for patients with CD30-positive peripheral T-cell lymphomas as shown by a significant improvement in progression-free survival and overall survival with a manageable safety profile. FUNDING: Seattle Genetics Inc, Millennium Pharmaceuticals Inc, a wholly owned subsidiary of Takeda Pharmacuetical Company Limited, and National Institutes of Health National Cancer Institute Cancer Center.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunoconjugados/administração & dosagem , Fatores Imunológicos/administração & dosagem , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Brentuximab Vedotin , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Método Duplo-Cego , Doxorrubicina/administração & dosagem , Feminino , Humanos , Imunoconjugados/efeitos adversos , Fatores Imunológicos/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Vincristina/administração & dosagem
6.
Semin Thromb Hemost ; 40(1): 34-40, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24381149

RESUMO

While clinical recognition of thrombotic thrombocytopenia purpura (TTP) has been evident for almost 90 years, the pathological basis of this disorder has only, relatively, recently been elucidated. Consequently, options for treating TTP had evolved rather slowly for many years. Despite this, current treatment practices of intensive plasma exchange often with immune modulation have seen survival rates increase dramatically. Nevertheless, the current understanding of TTP may witness the cusp of a new era for this disorder, with new and emerging treatments nearing clinical practice that specifically target the root cause of TTP. Some of these targeted approaches may even see the beginning of plasma-free treatments for TTP, with potentially faster recoveries and fewer long-term adverse effects.


Assuntos
Troca Plasmática/métodos , Troca Plasmática/tendências , Púrpura Trombocitopênica Trombótica/terapia , História do Século XX , História do Século XXI , Humanos , Troca Plasmática/história , Púrpura Trombocitopênica Trombótica/história
7.
Blood Adv ; 7(8): 1488-1495, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-36287231

RESUMO

Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the current standard therapy for patients with diffuse large B-cell lymphoma (DLBCL) and is curative in ∼60% of patients. Atezolizumab is a humanized immunoglobulin G1 monoclonal antibody that targets programmed death-ligand 1 and has previously shown antitumor activity in several tumor types. In a phase 1b/2 trial (NCT02596971), we evaluated the safety and efficacy of atezolizumab in combination with R-CHOP (atezo-R-CHOP; for 6-8 cycles) in patients with previously untreated DLBCL. Patients achieving a complete response (CR) at the end of induction received consolidation therapy with atezolizumab on day 1 of each 21-day cycle for an additional 17 cycles. Overall, 42 patients with DLBCL were included in this analysis. The primary endpoint, CR rate at the end of induction, as assessed by an independent review committee (modified Lugano 2014 criteria), was 77.5% (95% confidence interval [CI], 64.0-87.7; n = 40). Investigator-assessed progression-free survival and overall survival at 3 years were 77.4% (95% CI, 59.7-88.0) and 87.2% (95% CI, 71.9-94.5), respectively. All treated patients experienced ≥1 adverse event (AE; 32 patients [76.2%] had grade 3-4 AE). One patient had a fatal AE (unconfirmed progressive multifocal leukoencephalopathy) that was considered related to atezolizumab and rituximab, and 17 patients (40.5%) experienced atezolizumab-related AEs of special interest. In previously untreated patients with DLBCL, atezo-R-CHOP demonstrated encouraging clinical efficacy and a safety profile consistent with the known toxicities of the individual drugs. This trial was registered at www.clinicaltrials.gov as #NCT02596971.


Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Rituximab/efeitos adversos , Anticorpos Monoclonais Murinos , Anticorpos Monoclonais Humanizados/efeitos adversos , Vincristina/efeitos adversos , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Prednisona/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
8.
J Clin Oncol ; 41(33): 5107-5117, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37506346

RESUMO

PURPOSE: The combination of zanubrutinib plus obinutuzumab (ZO) was found to be well tolerated with an early signal of efficacy in a phase Ib study. ROSEWOOD is a phase II, randomized study that assessed the efficacy and safety of ZO versus obinutuzumab in patients with relapsed/refractory (R/R) follicular lymphoma (FL). METHODS: Patients with R/R FL who had received ≥2 lines of therapy, including an anti-CD20 antibody and an alkylating agent, were randomly assigned 2:1 to receive ZO or obinutuzumab (O). The primary end point was overall response rate (ORR) by independent central review (ICR). Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival, and safety. RESULTS: A total of 217 patients were randomized (ZO, 145; O, 72). Median study follow-up was 20.2 months. The study met its primary end point: ORR by ICR was 69% (ZO) versus 46% (O; P = .001). Complete response rate was 39% (ZO) versus 19% (O); 18-month DOR rate was 69% (ZO) versus 42% (O). Median PFS was 28.0 months (ZO) versus 10.4 months (O; hazard ratio, 0.50 [95% CI, 0.33 to 0.75]; P < .001). The most common adverse events with ZO were thrombocytopenia, neutropenia, diarrhea, and fatigue; incidences of atrial fibrillation and major hemorrhage were 3% and 1%, respectively. CONCLUSION: The combination of ZO met its primary end point of a superior ORR versus O, and demonstrated meaningful activity and a manageable safety profile in patients with R/R FL. ZO had a favorable benefit-risk profile compared with O, and represents a potential combination therapy for patients with R/R FL.


Assuntos
Linfoma Folicular , Piperidinas , Pirazóis , Pirimidinas , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Rituximab
9.
Chin Med ; 17(1): 16, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35073963

RESUMO

BACKGROUND: Parkinson's disease (PD) is a prevalent and debilitating condition. Conventional medications cannot control all symptoms and may inflict adverse effects. A survey reported that Chinese herbal medicine (CHM) is frequently sought. Existing CHM trials were contradictory and often of poor quality due to lack of methodological rigor. A national clinical guideline was drafted in China with diagnostic criteria and treatment strategy of Chinese medicine (CM) patterns subgroups of PD. The suggested CHM were found to exhibit neuroprotective effect in in vitro and in vivo studies. This trial aims to preliminarily assess the effect of CHM prescribed based on pattern differentiation on PD symptoms and patients' quality of life, and evaluate the feasibility of the trial design for a future large-scale trial. METHODS: This trial will be a pilot assessor- and data analyst blind, add-on, randomised, controlled, pragmatic clinical trial. 160 PD patients will be recruited and randomised into treatment or control groups in a 1:1 ratio. The trial will be conducted over 32 weeks. PD patients in the treatment group will be stratified into subgroups based on CM pattern and receive CHM accordingly in addition to conventional medication (ConM). The control group will receive ConM only. The primary outcome will be part II of the Movement Disorder Society Sponsored Revision of Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Secondary outcomes will include part and total scores of MDS-UPDRS, domain and total scores of Non-motor symptom scale (NMSS). Adverse events will be monitored by monthly follow-ups and questionnaires. Mixed models will be used to analyse data by Jamovi and R. EXPECTED OUTCOMES: The success of our trial will show that the pragmatic design with subgroup differentiation is feasible and can produce reliable results. It will also provide preliminary data of the effect of CHM on improving clinical outcomes and quality of PD patients. Data collected will be used to optimize study design of the future large-scale clinical study. ETHICAL CLEARANCE: Ethical clearance of this study was given by the Research Ethics Committee of Hong Kong Baptist University (REC/20-21/0206). Trial registration This trial is registered on ClinicalTrials.gov (NCT05001217, Date: 8/10/2021, https://clinicaltrials.gov/ct2/show/NCT05001217 ). Type of manuscript: clinical trial protocol (date: 3rd November, 2021, version 1).

10.
Blood Adv ; 6(20): 5659-5667, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-35359000

RESUMO

Obinutuzumab (G) chemoimmunotherapy demonstrated improved progression-free survival (PFS) vs rituximab-based chemoimmunotherapy in patients with previously untreated follicular lymphoma (FL) in the GALLIUM trial. Atezolizumab (atezo) is a programmed death-ligand 1 inhibitor with a complementary mechanism of action to G by restoring cytotoxic T-cell function. We evaluated the safety and efficacy of atezo-G-bendamustine in patients with previously untreated FL in a phase Ib/II trial (#NCT02596971). A safety run-in phase was followed by an expansion phase with atezo-G-bendamustine induction and atezo-G maintenance for ≤24 months. Forty patients with previously untreated FL were enrolled and treated with atezo-G-bendamustine. The primary endpoint, complete response (CR) rate, assessed by an independent review committee (IRC; modified Lugano 2014 criteria) was 75.0% (95% confidence interval [CI], 61.3% to 85.8%). Three-year investigator-assessed PFS and overall survival rates were 80.9% (95% CI, 63.9% to 90.5%) and 89.3% (95% CI, 73.9% to 95.9%), respectively. At baseline, 21/40 patients had circulating lymphoma-specific clonotypes and underwent repeat testing at end of induction; all were minimal residual disease negative (10-5 sensitivity), with 16 (76.2%) CRs, 3 (14.3%) partial responses, and 2 (9.5%) with stable disease (IRC assessed). Grade 5 (fatal) adverse events (AEs) were reported in 5 patients. The efficacy of atezo-G-bendamustine in previously untreated FL did not appear superior to G-bendamustine efficacy as seen in the GALLIUM trial, and the addition of atezo to G-bendamustine was associated with an increased risk of AEs. Particularly due to the unfavorable safety profile, this regimen cannot be recommended in patients with previously untreated FL. This trial was registered at www.clinicaltrials.gov as #NCT02596971.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Folicular , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/efeitos adversos , Gálio/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Rituximab/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos
11.
Blood Adv ; 6(19): 5550-5555, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-35470385

RESUMO

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of aggressive non-Hodgkin lymphomas, the majority of which have high relapse rates following standard therapy. Despite use of consolidative stem cell transplant (SCT) following frontline therapy, there remains no consensus on its utility. The double-blind randomized phase 3 ECHELON-2 study (#NCT01777152; clinicaltrials.gov) demonstrated improved progression-free survival (PFS) and overall survival with frontline brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP). Herein, we conducted an exploratory subgroups analysis of the impact of consolidative SCT on PFS in patients with previously untreated CD30+ PTCL (ALK- anaplastic large cell lymphoma [ALCL] and non-ALCL) who were in complete response (CR) after frontline treatment with A+CHP or cyclophosphamide, doxorubicin, vincristine, and prednisone. Median PFS follow-up was 47.57 months. The PFS hazard ratio was 0.36, equating to a 64% reduction in the risk of a PFS event in patients who underwent SCT. The median PFS in patients who underwent SCT was not reached, vs 55.66 months in patients who did not undergo SCT. PFS results favored the use of SCT in both ALK- ALCL and non-ALCL subgroups. These data support the consideration of consolidative SCT in patients with CD30+PTCL who achieve CR following treatment with A+CHP.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Anaplásico de Células Grandes , Brentuximab Vedotin , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Humanos , Antígeno Ki-1 , Linfoma Anaplásico de Células Grandes/induzido quimicamente , Linfoma Anaplásico de Células Grandes/terapia , Recidiva Local de Neoplasia , Prednisona/efeitos adversos , Vincristina/efeitos adversos
12.
Syst Rev ; 10(1): 127, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910623

RESUMO

INTRODUCTION: Massage is a popularly used complementary and alternative therapy. Previous randomised controlled trials have examined the effects of massage on children, and several systematic reviews have been conducted to synthesise these data. This study aims to assess and summarise the current evidence from published systematic reviews of controlled clinical trials on the practice of paediatric massage, specifically in infants and children aged < 5 years. METHODS: The online databases MEDLINE, Embase, Health Technology Assessment Database, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Allied and Complementary Medicine, China National Knowledge Infrastructure and Wanfang Data will be searched from the inception onwards for evidence of the treatment effects. We will include systematic reviews of randomised control trials evaluating the effects and safety of massage therapy in infants and children aged < 5 years. The primary outcomes will be any physical or psychological outcome, and adverse effects on children. Secondary outcomes will include any physical or psychological outcome on caregivers. Two reviewers will independently screen the articles for inclusion as per the eligibility criteria. They will extract information from the included studies and assess the methodological quality of the included studies. A table will be used to summarise of information of the included studies, which includes the basic information, method and findings. The methodological quality of the included systematic reviews will be assessed by A Measurement Tool to Assess Systematic Reviews version 2 (AMSTAR 2). Extracted data from the included studies will be collected and presented using narrative approach. The pooled effect estimates for meta-analysed outcomes will be extracted when possible. If there is a discrepancy in results of two or more reviews on the same topic, then the causes of such discrepancy will be further explored. DISCUSSION: This overview of systematic reviews will summarise the current evidence on massage, specifically for infants and children aged < 5 years. We will comprehensively present the positive effects and adverse effects of this intervention. Findings from this overview will be published in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: CRD42020186003 .


Assuntos
Terapias Complementares , Massagem , Criança , Pré-Escolar , China , Humanos , Lactente , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
13.
Leuk Lymphoma ; 62(2): 330-336, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33026266

RESUMO

We present a retrospective multicenter study of pralatrexate treatment outcomes in an Australian practice setting for patients with relapsed/refractory T-cell lymphoma who had failed 1+ systemic therapies, treated via a compassionate access program. Endpoints assessed included response rates, toxicities, and subsequent therapies. Progression-free survival (PFS), time to next treatment (TTNT), event-free survival (EFS), overall survival (OS), and time to best response, were assessed by Kaplan-Meier analysis. The study included 31 patients, with median age 69 years. We demonstrated ORR of 35.5% (n = 11), including 4 complete responses (13%) and 7 partial responses (23%). The predicted median OS was 10 months, with EFS of 9 months, and PFS of 9 months. Median TTNT was 8 months. Mucositis was the most commonly observed toxicity. This study - the second largest real-world cohort reported to date - underscores the importance of pralatrexate in relapsed/refractory T-cell lymphoma, as well as its acceptable toxicity profile.


Assuntos
Linfoma de Células T , Recidiva Local de Neoplasia , Idoso , Aminopterina/análogos & derivados , Austrália/epidemiologia , Humanos , Linfoma de Células T/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
14.
Front Psychol ; 11: 583319, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33519601

RESUMO

This paper reports on the long-term effectiveness of a non-formal co-curricular educational program based on a campus ecogarden at a Hong Kong university in developing pro-sustainability awareness, attitudes and behavior among undergraduate students. This service-based, nature-based experiential learning program, termed the Ecogarden Farmer and Biodiversity Surveyor, has been running at the university since 2015. The program is divided into two consecutive phases: a training phase comprising various learning activities and a successive internship phase consisting of the all-round practical tasks involved in managing the garden. A retrospective evaluation of the program using phenomenographic approach and content analysis was adopted to reveal the diversity of students' learning experience, as the indicators of the success of the program. Of 112 participants from 4 cohorts, 32 completed online questionnaires, and semi-structured interviews were successfully conducted with twelve participants, three from each of the four cohorts. The results indicated that the program's outcomes could be categorized into five themes. Most outcomes fit into the theme 'an increase in knowledge and skill level,' followed by 'rise in environmental awareness,''facilitation of personal growth,' and 'enhancement of career development.' Many structural experiences revealed may suggest the success of the program. The longer the participants had participated in the program, the more in-depth and diversified reflection of the senior participants relating to personal development were mentioned. This study provides critical insights into the validity of retrospective program evaluation for assessing the long-term impact of EfS programs by introducing a cross-sectional study of different cohorts as a serial time-point sampling strategy.

15.
Sleep Med ; 74: 18-24, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32836181

RESUMO

OBJECTIVE: The COVID-19 pandemic is a large-scale public health emergency that likely precipitated sleep disturbances in the community. This study aimed to investigate the prevalence and correlates of sleep disturbances during the early phase of COVID-19 pandemic. METHODS: This web-based cross-sectional study recruited 1138 Hong Kong adults using convenience sampling over a two-week period from 6th April 2020. The survey collected data on sleep disturbances, mood, stress, stock of infection control supplies, perceived risk of being infected by COVID-19, and sources for acquiring COVID-19 information. The participants were asked to compare their recent sleep and sleep before the outbreak. The Insomnia Severity Index (ISI) was used to assess their current insomnia severity. Prevalence was weighted according to 2016 population census. RESULTS: The weighted prevalence of worsened sleep quality, difficulty in sleep initiation, and shortened sleep duration since the outbreak were 38.3%, 29.8%, and 29.1%, respectively. The prevalence of current insomnia (ISI score of ≥10) was 29.9%. Insufficient stock of masks was significantly associated with worsened sleep quality, impaired sleep initiation, shortened sleep duration, and current insomnia in multivariate logistic regression (adjusted OR = 1.57, 1.72, 1.99, and 1.96 respectively, all p < 0.05). CONCLUSION: A high proportion of people in Hong Kong felt that their sleep had worsened since the COVID-19 outbreak. Insufficient stock of masks was one of the risk factors that were associated with sleep disturbances. Adequate and stable supply of masks may play an important role to maintain the sleep health in the Hong Kong general population during a pandemic outbreak.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Pneumonia Viral/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , População Urbana , Adolescente , Adulto , Idoso , COVID-19 , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Estudos Transversais , Surtos de Doenças/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Prevalência , SARS-CoV-2 , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/terapia , População Urbana/tendências , Adulto Jovem
17.
Waste Manag Res ; 21(5): 436-47, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14661891

RESUMO

Although landfill gas emission can be greatly reduced by extraction and converting gas to energy, in practice not all gas can be collected and some leaks can still occur. Management of landfill gas can be improved if leaks can be detected and rectified effectively. This paper provides a brief review of methods available for detecting landfill leakage, with a focus on infrared thermography. It then describes a study which was conducted to test if an infrared camera can be used to detect gas leaks accurately by identifying them as anomalies. It examined the applicability and limitations of the technique by investigating fundamental factors such as weather conditions, ground conditions and distance of sensor from source. The paper also describes a test case conducted to reinforce the findings. It concluded that unless all the fundamental factors are clearly understood and addressed, the technique currently can only be used as a screening tool rather than as a precise tool to detect landfill gas leakages. For this reason, it would be difficult to use the technique as a basis for modelling gas emission from landfills.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/prevenção & controle , Eliminação de Resíduos/métodos , Termografia/métodos , Monitoramento Ambiental/métodos , Gases
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