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A decade after International Myeloma Working Group (IMWG) biomarkers (SLiM criteria) were introduced, this real-world study examined their impact on diagnosis, therapy and outcomes in myeloma. Using the ANZ MRDR, 3489 newly diagnosed patients from 2013 to 2023, comprising 3232 diagnosed by CRAB ('CRAB patients', including 1758 who also satisfied ≥1 SLiM criteria) and 257 by SLiM ('SLiM patients') criteria were analysed. CRAB patients had higher R-ISS and lower performance status, with no difference in cytogenetic risk. SLiM patients had improved progression-free survival (PFS, 37.5 vs. 32.2 months, hazard ratio [HR] 1.31 [1.08-1.59], p = 0.003), overall survival (80.9 vs. 73.2 months, HR 1.64 [1.26-2.13], p < 0.001) and PFS2 (54.6 vs. 40.3 months, HR 1.51 [1.22-1.86], p < 0.001) compared with CRAB patients, partially explained by earlier diagnosis, with no differential impact between the plasma cell and light-chain criteria on PFS. However, 34% of CRAB patients did not manifest SLiM characteristics, raising the possibility that SLiM features are associated with different biological behaviours contributing to a better prognosis, for example, improved PFS2 in SLiM patients suggested less disease resistance at first relapse. These data support earlier initiation of therapy by SLiM. The superior survival outcomes of SLiM versus CRAB patients highlight the importance of defining these subgroups when interpreting therapeutic outcomes at induction and first relapse.
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The frequency and causes of early mortality in patients with newly diagnosed multiple myeloma (NDMM) have not been well described in the era of novel agents. We investigated early mortality in a prospective cohort study of all patients with NDMM registered on the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) at 36 institutions between July 2011 and March 2020. Early mortality was defined as death from any cause within the first 12 months after diagnosis. A total of 2377 patients with NDMM were included in the analysis, with a median (interquartile range) age of 67.4 (58.9-74.60 years, and 60% were male. Overall, 216 (9.1%) patients died within 12 months, with 119 (4.5%) having died within 6 months. Variables that were independent predictors of early mortality after adjustment in multivariable regression included age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.05-1.08; p < 0.001), Eastern Cooperative Oncology Group performance status (OR 1.50, 95% CI 1.26-1.79; p < 0.001), serum albumin (OR 0.95, 95% CI 0.93-0.98; p < 0.001), cardiac disease (OR 1.96, 95% CI 1.35-2.86; p < 0.001) and International Staging System (OR 1.40, 95% CI 1.07-1.82; p = 0.01). For those with a primary cause of death available, it was reported as disease-related in 151 (78%), infection 13 (7%), other 29 (15%). Infection was listed as a contributing factor for death in 38% of patients.
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Mieloma Múltiplo , Idoso , Austrália/epidemiologia , Feminino , Humanos , Masculino , Nova Zelândia/epidemiologia , Estudos Prospectivos , Sistema de RegistrosRESUMO
The proinflammatory cytokine storm associated with coronavirus disease 2019 (COVID-19) negatively affects the hematological system, leading to coagulation activation and endothelial dysfunction and thereby increasing the risk of venous and arterial thrombosis. Coagulopathy has been reported as associated with mortality in people with COVID-19 and is partially reflected by enhanced D-dimer levels. Poor vascular health, which is associated with the cardiometabolic health conditions frequently reported in people with severer forms of COVID-19, might exacerbate the risk of coagulopathy and mortality. Sedentary lifestyles might also contribute to the development of coagulopathy, and physical activity participation has been inherently lowered due to at-home regulations established to slow the spread of this highly infectious disease. It is possible that COVID-19, coagulation, and reduced physical activity may contribute to generate a "perfect storm," where each fuels the other and potentially increases mortality risk. Several pharmaceutical agents are being explored to treat COVID-19, but potential negative consequences are associated with their use. Exercise is known to mitigate many of the identified side effects from the pharmaceutical agents being trialled but has not yet been considered as part of management for COVID-19. From the limited available evidence in people with cardiometabolic health conditions, low- to moderate-intensity exercise might have the potential to positively influence biochemical markers of coagulopathy, whereas high-intensity exercise is likely to increase thrombotic risk. Therefore, low- to moderate-intensity exercise could be an adjuvant therapy for people with mild-to-moderate COVID-19 and reduce the risk of developing severe symptoms of illness that are associated with enhanced mortality.
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Coagulação Sanguínea , Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Exercício Físico , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Anticoagulantes/uso terapêutico , Betacoronavirus , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , COVID-19 , Infecções por Coronavirus/complicações , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinólise , Hemostasia , Humanos , Inflamação , Pandemias , Pneumonia Viral/complicações , Risco , SARS-CoV-2 , Trombose/sangue , Trombose/complicaçõesRESUMO
A previous study found that platelet recovery and mortality were worse in recipients of myeloablative bone marrow transplants where graft transit times were longer than 20 hours. This retrospective study of unrelated myeloablative allogeneic transplantation performed within Australia and New Zealand analyzed transplant outcomes according to graft transit times. Of 233 assessable cases, 76 grafts (33%) were sourced from bone marrow (BM) and 157 (67%) from peripheral blood. Grafts sourced from Australia and New Zealand (47% of total) were associated with a median transit time of 6 hours versus 32 hours for overseas sourced grafts (53% of total). Graft transit temperature was refrigerated in 85%, ambient in 6%, and unknown in 9% of cases, respectively. Graft transit times had no significant effect on neutrophil or platelet engraftment, treatment-related mortality, overall survival, and incidence of acute or chronic graft-versus-host disease. Separate analysis of BM grafts, although of reduced power, also showed no significant difference in either neutrophil or platelet engraftment or survival between short and longer transport times. This study gives reassurance that both peripheral blood stem cell and especially BM grafts subjected to long transit times and transported at refrigerated temperatures may not be associated with adverse recipient outcomes.
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Transplante de Medula Óssea/métodos , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas/métodos , Meios de Transporte , Adolescente , Adulto , Austrália , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Sistema de Registros , Estudos Retrospectivos , Temperatura , Fatores de Tempo , Adulto JovemRESUMO
The combination of lenalidomide and dexamethasone is an established treatment for patients with multiple myeloma (MM). Increasingly, treatment attenuation is advocated for frail/elderly patients to minimize toxicity even though there have been no prospective studies to demonstrate whether lenalidomide dose attenuation impacts on response and survival outcome. This prospective multicentre phase II study assessed the efficacy and tolerability of lower dose lenalidomide (15 mg) and dexamethasone (20 mg) in 149 eligible patients with relapsed/refractory MM aged over 59 years and/or with renal impairment. The overall response rate was 71% (complete response 15%). Median (range) progression-free survival (PFS) and overall survival (OS) were 8·9 (6·9-11·5) and 30·5 (20·0-36·2) months, respectively. Upon formal statistical comparison of these endpoints to that of a matched cohort of patients from the pivotal phase III MM009/MM010 studies who received standard-dose lenalidomide (25 mg) and high-dose dexamethasone (40 mg) no difference was seen in PFS (P = 0·34) and OS (P = 0·21). Importantly, grade 3-4 toxicities were reduced with low-dose lenalidomide, mainly lower neutropenia (29% vs. 41%), infections (23% vs. 31%) and venous thromboembolism (3% vs. 13%). This study supports a strategy of lenalidomide dose reduction at the outset for at-risk patients, and prospectively confirms that such an approach reduces adverse events while not compromising patient response or survival outcomes.
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Inibidores da Angiogênese/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/administração & dosagem , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Lenalidomida , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Recidiva , Talidomida/administração & dosagem , Talidomida/efeitos adversosRESUMO
BACKGROUND: Plasma cell dyscrasias (PCD) are a spectrum of disorders resulting from the clonal expansion of plasma cells, ranging from the pre-malignant condition monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). MM generates a significant burden of disease on the community and it is predicted that it will increase in both incidence and prevalence owing to an ageing population and longer survival secondary to new therapeutic options. Robust and comprehensive clinical data are currently lacking but are required to define current diagnostic, investigational and management patterns in Australia and New Zealand (ANZ) for comparison to both local and international guidelines for standards of care. A clinical registry can provide this information and subsequently support development of strategies to address any differences, including providing a platform for clinical trials. The Myeloma and Related Diseases Registry (MRDR) was developed to monitor and explore variations in practices, processes and outcomes in ANZ and provide benchmark outcomes nationally and internationally for PCD. This paper describes the MRDR aims, development and implementation and discusses challenges encountered in the process. METHODS: The MRDR was established in 2012 as an online database for a multi-centre collaboration across ANZ, collecting prospective data on patients with a diagnosis of MGUS, MM, solitary plasmacytoma or plasma cell leukaemia. Development of the MRDR required multi-disciplinary team participation, IT and biostatistical support as well as financial resources. RESULTS: More than 1250 patients have been enrolled at 23 sites to date. Here we describe how database development, data entry and securing ethics approval have been major challenges for participating sites and the coordinating centre, and our approaches to resolving them. Now established, the MRDR will provide clinically relevant and credible monitoring, therapy and 'real world' outcome data, to support the conduction of high quality studies. In addition, the Myeloma 1000 sub-study is establishing a repository of paired peripheral blood specimens from registry patients to study mechanisms underlying disease progression. CONCLUSION: Establishment of the MRDR has been challenging, but it is a valuable investment that will provide a platform for coordinated national and international collaboration for clinical research in PCD in ANZ.
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Bases de Dados Factuais/estatística & dados numéricos , Mieloma Múltiplo/epidemiologia , Paraproteinemias/epidemiologia , Sistema de Registros/estatística & dados numéricos , Austrália/epidemiologia , Progressão da Doença , Humanos , Incidência , Informática Médica/métodos , Informática Médica/estatística & dados numéricos , Nova Zelândia/epidemiologia , PrevalênciaRESUMO
BACKGROUND: We aimed to assess efficacy and tolerability of vorinostat in combination with bortezomib for treatment of patients with relapsed or refractory multiple myeloma. METHODS: In our randomised, double-blind, placebo-controlled, phase 3 trial, we enrolled adults (≥18 years) at 174 university hospitals in 31 countries worldwide. Eligible patients had to have non-refractory multiple myeloma that previously responded to treatment (one to three regimens) but were currently progressing, ECOG performance statuses of 2 or less, and no continuing toxic effects from previous treatment. We excluded patients with known resistance to bortezomib. We randomly allocated patients (1:1) using an interactive voice response system to receive 21 day cycles of bortezomib (1·3 mg/m(2) intravenously on days 1, 4, 8, and 11) in combination with oral vorinostat (400 mg) or matching placebo once-daily on days 1-14. We stratified patients by baseline tumour stage (International Staging System stage 1 or stage ≥2), previous bone-marrow transplantation (yes or no), and number of previous regimens (1 or ≥2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed adverse events in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number 00773747. FINDINGS: Between Dec 24, 2008, and Sept 8, 2011, we randomly allocated 317 eligible patients to the vorinostat group (315 of whom received at least one dose) and 320 to the placebo group (all of whom received at least one dose). Median PFS was 7·63 months (95% CI 6·87-8·40) in the vorinostat group and 6·83 months (5·67-7·73) in the placebo group (hazard ratio [HR] 0·77, 95% CI 0·64-0·94; p=0·0100). 312 (99%) of 315 patients in the vorinostat group and 315 (98%) of 320 patients in the placebo group had adverse events (300 [95%] adverse events in the vorinostat group and 282 [88%] in the control group were regarded as related to treatment). The most common grade 3-4 adverse events were thrombocytopenia (143 [45%] patients in the vorinostat group vs 77 [24%] patients in the placebo group), neutropenia (89 [28%] vs 80 [25%]), and anaemia (53 [17%] vs 40 [13%]). INTERPRETATION: Although the combination of vorinostat and bortezomib prolonged PFS relative to bortezomib and placebo, the clinical relevance of the difference in PFS between the two groups is not clear. Different treatment schedules of bortezomib and vorinostat might improve tolerability and enhance activity. FUNDING: Merck.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácidos Borônicos/administração & dosagem , Bortezomib , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Pirazinas/administração & dosagem , Taxa de Sobrevida , VorinostatRESUMO
Serious infection is common in patients with multiple myeloma due to immune deficiency from the underlying disease and/or its treatment. Immunoglobulin replacement is one approach to reduce infection risk in these patients. However, few real-world data exist on its use in patients with myeloma. We investigated immunoglobulin use in Australia, New Zealand and Asia-Pacific using registry data and explored its association with survival outcomes. A total of 2374 patients with a median follow-up time of 29.5 months (interquartile range 13.3-54.3 months) were included in the analysis - 1673 from Australia, 313 Korea, 281 New Zealand and 107 Singapore. Overall, 7.1% of participants received immunoglobulin replacement within 24 months of diagnosis. Patients who received immunoglobulin replacement were likely to be younger, had lower baseline IgG levels (excluding paraprotein), were more likely to have baseline hypogammaglobulinaemia, baseline severe hypogammaglobulinaemia and abnormal baseline fluorescent in-situ hybridisation status, receive first-line myeloma treatment with immunomodulatory drugs or anti-CD38 therapy and undergo upfront autologous stem cell transplant. In our patient cohort, the use of immunoglobulin was not associated with overall survival benefit at the time of last follow-up (adjusted hazard ratio 0.72, 95% CI 0.46-1.14, p = 0.16). Understanding treatment approaches in clinical practice can help support future planning and provision of immunoglobulin resources.
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PURPOSE: Treatment of non-Hodgkin lymphoma (NHL) with cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP) is known to be associated with a significant risk of febrile neutropenia (FN) of up to 50% [Osby et al. 2003 Blood 101(10): 3840-3848; Lyman and Delgado 2003 Cancer 98(11): 2402-2409]. This study sought to examine the impact of primary granulocyte colony-stimulating factor (GCSF) prophylaxis on the incidence of FN, quality of life and overall cost. METHODS: In this retrospective cohort study, a group of 65 consecutive patients who received CHOP chemotherapy for NHL between December 2006 and October 2009 was studied. Patients either received filgrastim (300 mcg, average of seven doses), pegylated filgrastim (6 mg, single dose), or no GCSF prophylaxis. In addition, 19 patients were asked to complete Functional Assessment of Cancer Therapy: General quality-of-life questionnaires. RESULTS: Overall, patients who received primary GCSF prophylaxis had significantly fewer FN compared to those who did not (5 vs. 60%, p < 0.0001; numbers needed to treat of 1.8; 95% confidence interval, 1.6-2.9). Cost-benefit analysis showed that the GCSF prophylaxis was associated with only a small increase in direct financial cost ($238 NZD [US$189] more to give primary GCSF prophylaxis per patient vs. no prophylaxis). The quality of life assessment showed that the patients' quality of life scores were similar to the published data from the validation study population (466 patients with mixed cancers) for Functional Assessment of Cancer Therapy. CONCLUSIONS: Our study shows that primary GCSF prophylaxis is effective in preventing FN in patients receiving CHOP chemotherapy for NHL without adversely affecting their quality of life, and is cost effective.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Análise Custo-Benefício , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Febre/induzido quimicamente , Febre/epidemiologia , Febre/prevenção & controle , Filgrastim , Fator Estimulador de Colônias de Granulócitos/economia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Neutropenia/prevenção & controle , Polietilenoglicóis , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Qualidade de Vida , Proteínas Recombinantes/economia , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Inquéritos e Questionários , Vincristina/efeitos adversos , Vincristina/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: Maori and Pacific peoples (MPP) in New Zealand (NZ) have poorer health outcomes than other ethnicities. However, this has not been clinically investigated in multiple myeloma (MM). Using data from the Australian and NZ Myeloma and Related Diseases Registry for all participating centers in NZ, we compared MPP demographics, clinical characteristics, diagnostics, treatment, and outcomes to non-MPP. PATIENTS AND METHODS: MPP were defined as having ≥1 grandparent of this heritage. We tested ethnicity as a predictor of overall survival (OS) with multivariable Cox regression. RESULTS: Of 568 NZ patients with MM (September 2012 to April 2021) and ethnicity data, 138 were MPP. They were diagnosed younger than non-MPP (median age 63 [IQR: 57-72] vs. 70y [62-77], P < .001). Obesity (53 vs. 27%, P < .001), diabetes (24 vs. 8%, P < .001), renal insufficiency (28 vs. 17%, P = .005), pulmonary disease (10 vs. 5%, P = .02) and FISH abnormalities (54 vs. 42%, P = .04) were more common in MPP, and a lower proportion received first-line drug therapy (88 vs. 94%, P = .03) and autologous stem cell transplant (ASCT) (age <70y: 56 vs. 70%, P = .03). OS for MPP was shorter than non-MPP even after adjusting for age, comorbidities, disease stage, performance status, FISH abnormalities and treatment (HR 1.58 [1.04-2.39], P = .03). CONCLUSION: MPP with MM in NZ were younger, a greater proportion had comorbidities and FISH abnormalities at diagnosis, fewer received first-line treatment and/or ASCT, and they had poorer OS than non-MPP. Investigation of modifiable factors to improve outcomes and discern why MM occurs at a younger age in MPP is needed.
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Etnicidade , Mieloma Múltiplo , Austrália/epidemiologia , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Havaiano Nativo ou Outro Ilhéu do Pacífico , Nova Zelândia/epidemiologia , Sistema de RegistrosRESUMO
Supported by clinical trial proven survival benefit, clinical guidelines recommend upfront autologous stem cell transplantation (ASCT) for eligible MM patients. However, reported real-world utilisation is lower than expected (40-60%). We reviewed ASCT utilisation, demographics and outcomes for MM patients (≤70 years, ≥12-month follow-up) enroled onto the Australian/New Zealand MRDR from June 2012 to May 2020. In 982 patients (<65 years: 684, 65-70 years: 298), ASCT utilisation was 76% overall (<65 years: 83%, 65-70 years: 61%, front-line therapy: 67%). Non-ASCT recipients were older (median age: 65 years vs 60 years, p < 0.001), had more comorbidities (cardiac disease: 16.9% vs 5.4%, p < 0.001; diabetes: 19.1% vs 7.0%, p < 0.001; renal dysfunction: median eGFR(ml/min): 68 vs 80, p < 0.001), inferior performance status (ECOG ≥ 2: 26% vs 13%, p < 0.001) and higher-risk MM (ISS-3: 37% vs 26%, p = 0.009, R-ISS-3 18.6% vs 11.8%, p = 0.051) than ASCT recipients. ASCT survival benefit (median progression-free survival (PFS): 45.3 months vs 35.2 months, p < 0.001; overall survival (OS): NR vs 64.0 months, p < 0.001) was maintained irrespective of age (<65 years: median PFS: 45.3 months vs 37.7 months, p = 0.04, OS: NR vs 68.2 months, p = 0.002; 65-70 years: median PFS: 46.7 months vs 29.2 months, p < 0.001, OS: 76.9 months vs 55.6 months, p = 0.005). This large, real-world cohort reaffirms ASCT survival benefit, including in 'older' patients necessitating well-designed studies evaluating ASCT in 'older' MM to inform evidence-based patient selection.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Idoso , Austrália , Intervalo Livre de Doença , Humanos , Mieloma Múltiplo/terapia , Nova Zelândia , Sistema de Registros , Estudos Retrospectivos , Transplante Autólogo , Resultado do TratamentoRESUMO
BACKGROUND: Real-world multiple myeloma (MM) data are scarce, with most data originating from clinical trials. The Myeloma and Related Diseases Registry (MRDR) is a prospective clinical-quality registry of newly diagnosed cases of plasma cell disorders established in 2012 and operating at 44 sites in Australia and New Zealand as of April 2020. METHODS: We reviewed all patients enrolled onto the MRDR between June 2012 and April 2020. Baseline characteristics, treatment, and outcome data were reviewed for MM patients with comparisons made by chi-square tests (categorical variables) and rank sum tests (continuous variables). Kaplan-Meier analysis was used to estimate progression-free survival and overall survival (OS). RESULTS: As of April 2020, a total of 2405 MM patients were enrolled (median age, 67 years, with 40% aged > 70 years). High-risk features were present in 13% to 31% of patients: fluorescence in-situ hybridization (FISH) ≥ 1 of t(4;14), t(14;16), or del(17p) 18%, International Staging System (ISS)-3 31%, and Revised ISS (R-ISS)-3 13%. Cytogenetic/FISH analyses were performed in 50% and 68% of patients, respectively, with an abnormal karyotype result in 34%. Bortezomib-containing therapy was the most common first-line therapy (79.3%, n = 1706). Patients not receiving bortezomib were older (median age, 76 vs 65 years, P < .001) with inferior performance status (Eastern Cooperative Oncology Group performance status ≥ 2, 41% vs 18%, P < .001). Median progression-free survival and OS were 30.8 and 65.8 months, respectively. Younger patients had superior OS (76.3 vs 46.7 months, P < .001, < 70 and ≥ 70 years, respectively). R-ISS score was available in 50.7% (n = 1220) of patients, and higher R-ISS was associated with inferior OS (R-ISS-1 vs R-ISS-2 vs R-ISS-3: not reached vs 68.1 months vs 33.2 months, respectively, P < .001). CONCLUSION: Clinical registries provide a more complete picture of MM diagnosis and treatment, and highlight the challenges of adhering to best practices in a real-world context.
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Mieloma Múltiplo/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Tomada de Decisão Clínica , Terapia Combinada , Comorbidade , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Gamopatia Monoclonal de Significância Indeterminada/terapia , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/terapia , Nova Zelândia/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Vigilância em Saúde Pública , Sistema de RegistrosRESUMO
BACKGROUND: Common variable immunodeficiency disorders (CVID) are a rare group of primary immune defects, where the underlying cause is unknown. Approximately 10-20% of patients with typical CVID have a granulomatous variant, which has closely overlapping features with sarcoidosis. CASE PRESENTATION: Here we describe a young man who sequentially developed refractory Evans syndrome, cauda equina syndrome and most recently renal impairment. Following immunosuppression, he has made a recovery from all three life-threatening autoimmune disorders. As the patient was hypogammaglobulinemic for most of the time while on immunosuppression, vaccine challenges and other tests were not possible. Histological features were in keeping with sarcoidosis rather than the granulomatous variant of CVID. In the brief period when immunosuppression was lifted between the cauda equina syndrome and renal impairment, he normalised his immunoglobulins, confirming sarcoidosis rather than CVID was the underlying cause. CONCLUSION: We discuss diagnostic difficulties distinguishing the two conditions, and the value of histological features in our diagnostic criteria for CVID in identifying sarcoidosis, while the patient was hypogammaglobulinemic. The key message from this case report is that the characteristic histological features of CVID can be very helpful in making (or excluding) the diagnosis, particularly when other tests are not possible.
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BACKGROUND: Renal impairment (RI) is a common complication of multiple myeloma (MM) and remains a poor prognostic factor despite improved survival with newer therapies. PATIENTS AND METHODS: We evaluated baseline characteristics, treatment, and outcomes of newly diagnosed MM patients with RI at diagnosis in the Australia and New Zealand Myeloma and Related Diseases Registry over 5 years to April 2018; we compared patients with RI (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2) with those with eGFR ≥60. In autologous stem cell transplantation (ASCT) analyses, patients aged 70 years and younger and ≥1 year from diagnosis were included. RESULTS: Overall, 36% of patients with newly diagnosed MM had RI; they were older, had more advanced disease and comorbidities, and worse performance status. Bortezomib-based induction therapy was most commonly used, although administered to fewer RI patients, despite similar response rates. Patients with RI were less likely to receive ASCT; however, recipients had longer progression-free survival (PFS) and overall survival (OS). Patients with RI had shorter OS and PFS after adjusting for age. In ASCT recipients with RI versus no RI, there was no difference in PFS and OS. CONCLUSION: Our findings in "real world" MM patients with RI confirm that patient-, disease-, and treatment-related factors (such as suboptimal bortezomib and ASCT use), and delays in commencing therapy, might contribute to poorer outcomes, and support the use of ASCT in patients with RI.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/mortalidade , Mieloma Múltiplo/mortalidade , Sistema de Registros/estatística & dados numéricos , Insuficiência Renal/mortalidade , Adolescente , Adulto , Idoso , Austrália , Bortezomib/administração & dosagem , Criança , Pré-Escolar , Terapia Combinada , Dexametasona/administração & dosagem , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Oligopeptídeos/administração & dosagem , Prognóstico , Estudos Prospectivos , Insuficiência Renal/etiologia , Insuficiência Renal/patologia , Insuficiência Renal/terapia , Taxa de Sobrevida , Transplante Autólogo , Adulto JovemRESUMO
BACKGROUND: Pomalidomide and dexamethasone is a standard of care for patients with multiple myeloma in whom bortezomib and lenalidomide treatment has failed. KEYNOTE-183 assessed efficacy and safety of pomalidomide and dexamethasone with or without pembrolizumab in patients with relapsed or refractory multiple myeloma. Here, we present the findings of an unplanned, ad-hoc interim analysis at the request of the US Food and Drug Administration (FDA). METHODS: KEYNOTE-183 was a randomised, open-label, phase 3 trial done at 97 medical centres across 11 countries (Australia, Canada, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Spain, and USA). Patients aged at least 18 years with multiple myeloma, an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, previously treated with at least two lines of therapy (excluding pomalidomide) and refractory to the last line were randomly assigned 1:1 to the pembrolizumab plus pomalidomide and dexamethasone group or the pomalidomide and dexamethasone group via an interactive voice response or integrated web response system. Patients received oral pomalidomide 4 mg daily on days 1-21 and oral low-dose dexamethasone 40 mg on days 1, 8, 15, and 22 in 28-day cycles, with or without intravenous pembrolizumab 200 mg every 3 weeks. The dual primary endpoints were progression-free survival and overall survival. Efficacy was assessed in all randomly assigned patients and safety was assessed in patients who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov, number NCT02576977, and it is closed for accrual. FINDINGS: Between Jan 18, 2016, and June 7, 2017, 249 patients were randomly assigned to either the pembrolizumab plus pomalidomide and dexamethasone group (n=125) or the pomalidomide and dexamethasone group (n=124). On July 3, 2017, the FDA established that risks associated with the triple combination outweighed benefits and halted the study. Median follow-up was 8·1 months (IQR 4·5-10·9). Median progression-free survival was 5·6 months (95% CI 3·7-7·5) in the pembrolizumab plus pomalidomide and dexamethasone group versus 8·4 months (5·9-not reached) in the pomalidomide and dexamethasone group; progression-free survival estimates at 6 months were 48% (95% CI 37-58) versus 60% (49-69) at 6 months (hazard ratio [HR] 1·53; 95% CI 1·05-2·22; p=0·98). Median overall survival was not reached (95% CI 12·9-not reached) versus 15·2 months (12·7-not reached; HR 1·61; 95% CI 0·91-2·85; p=0·95); overall survival estimates at 6 months were 82% (95% CI 74-88) versus 90% (82-95). Serious adverse events occurred in 75 (63%) of 120 patients in the pembrolizumab plus pomalidomide and dexamethasone group versus 56 (46%) of 121 patients in the pomalidomide and dexamethasone group. Four (3%) treatment-related deaths occurred in the pembrolizumab plus pomalidomide and dexamethasone group (one each of unknown cause, neutropenic sepsis, myocarditis, and Stevens-Johnson syndrome); myocarditis and Stevens-Johnson syndrome were considered related to pembrolizumab. No treatment-related deaths were reported in the pomalidomide and dexamethasone group. INTERPRETATION: The results from this unplanned, FDA-requested, interim analysis showed that the benefit-risk profile of pembrolizumab plus pomalidomide and dexamethasone is unfavourable for patients with relapsed or refractory multiple myeloma. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co (Kenilworth, NJ, USA).
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Miocardite/etiologia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Recidiva , Síndrome de Stevens-Johnson/etiologia , Taxa de Sobrevida , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Resultado do TratamentoRESUMO
AIM: The aim of this study was to examine a potential ethnic disparity in the phenotype of polycythaemia vera (PV) between New Zealand European and Polynesian patients. METHOD: A retrospective review of medical records was conducted at Middlemore Hospital to identify adult patients with PV diagnosed between 1987 and 2007. Data extracted included diagnostic criteria, ethnicity, age, complications and survival. RESULTS: Eighty-eight adult patients with PV were identified during 1987-2007, 49 (55.7%) were Europeans and 36 (40.9%) Polynesians. The most striking finding was that Polynesian patients presented almost 14 years younger than Europeans (mean age of 54 years versus [vs] 68, respectively; P<.001). The white cell and platelet counts were higher in Polynesians compared with Europeans (mean white cell count of 22x109/L vs 13x109/L; mean platelet count of 648x109/L vs 512x109/L, respectively; P<.05 for both). The rate of JAK2 V617F mutation in Polynesians was 96%, equivalent to other large cohorts of European patients. The rates of long-term complications were comparable between Polynesians and Europeans, but the predicted impact on life expectancy was more severe for Polynesians. CONCLUSION: New Zealand Polynesian patients present with a distinctive PV phenotype. Their younger age at presentation suggests a different risk factor profile or a higher genetic susceptibility. We hope our observations initiate larger epidemiological and genetic studies to help elucidate the cause.
Assuntos
Havaiano Nativo ou Outro Ilhéu do Pacífico , Policitemia Vera/etnologia , Adulto , Idoso , Feminino , Seguimentos , Disparidades nos Níveis de Saúde , Hemoglobinas/análise , Humanos , Janus Quinase 2/genética , Leucemia Mieloide Aguda/epidemiologia , Contagem de Leucócitos , Expectativa de Vida , Masculino , Pessoa de Meia-Idade , Mutação , Nova Zelândia/epidemiologia , Contagem de Plaquetas , Policitemia Vera/genética , Policitemia Vera/mortalidade , Mielofibrose Primária/epidemiologia , Estudos Retrospectivos , EsplenomegaliaRESUMO
AIMS: This audit aimed to assess how frequently overnight transfusions were taking place and compare it to the previous 2004 audit. METHOD: All red cell units transfused between 20:00 and 08:00 hours in low acuity areas over 4 weeks in 2010 in 8 of New Zealand's largest public hospitals were identified prospectively, followed by review of clinical notes and laboratory results by the hospital Transfusion Nurse Specialist (TNS). RESULTS: 535 red cell units were transfused overnight, or 9% of the total units administered over the study period. Indications for transfusion were symptomatic anaemia, active bleeding or haemolysis (66%), but 16% of patients were asymptomatic. Of the non-urgent overnight transfusions (OTs), 42% were assessed as non-essential during the night. 49% of post-transfusion haemoglobin (Hb) levels were >100 g/L indicating a liberal transfusion practice. Although frequently cited as a reason for OT, only 16% of patients were discharged the following day. The median interval from pre-transfusion haemoglobin testing and starting the OT was approximately 9 hours, far exceeding the time needed to obtain routine full blood results. Adherence to recommended best transfusion practice was poor at night, with 12% of transfusions exceeding the 4 hour recommendation. End of transfusion observations fell to less than 80%, with the lowest compliance rate (69%) occurring at 06:00 hours. In addition to the 4 adverse reactions reported to the Haemovigilance programme, another 9 unreported reactions were identified by the auditors from the clinical notes. CONCLUSIONS: This audit has shown an improvement from 22% to 9% in the rate of OT compared to the 2004 audit. Nevertheless, 42% of transfusions were not considered appropriate based on current guidelines, and there is therefore room for improvement. A mean delay of 9 hours from haemoglobin sampling to transfusion suggests that reasons for this delay could be explored to help optimise transfusion start time. Some aspects of OT were worse than previously, with 12% of the OT exceeding 4 hours duration, double the rate of the previous audit. Results showing poor documentation and a high rate of unreported transfusion reactions (69% of reactions) suggest if an adverse transfusion reaction occurs overnight, there is a significant risk that it is less likely to be recognised, treated and/or reported.
Assuntos
Anemia/terapia , Doenças Assintomáticas/terapia , Transfusão de Sangue/estatística & dados numéricos , Hemorragia/terapia , Hospitais Públicos/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Hemolítica/terapia , Criança , Pré-Escolar , Dispneia/epidemiologia , Feminino , Humanos , Lactente , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Nova Zelândia , Privação do Sono , Fatores de Tempo , Reação Transfusional/epidemiologia , Adulto JovemRESUMO
AIM: To describe iron status at birth in a population sample of children. METHOD: Cord blood samples were obtained at birth from 131 infants enrolled in the cohort study Growing Up in New Zealand. Cord blood serum ferritin (SF) and haemoglobin (Hb) concentrations were measured and associations of SF and Hb with maternal and birth characteristics were determined. RESULTS: Demographics were comparable to the larger cohort, except for having a higher pre-pregnancy body mass index (26.9 vs. 25.4 kg/m2, P=0.005), lower frequency of cigarette smoking during pregnancy (2% vs. 11%, P=0.0004), and smaller proportion with birth-weight <2500 g (0% vs. 5%, P=0.03). Median (interquartile range) SF was 135 (88-180) mcg/L and mean (plus or minus SD) Hb was 160 plus or minus 17 g/L. Eight newborns (7%) had cord SF levels indicative of iron deficiency (SF <35 mcg/L), two newborns were anaemic (Hb <130 g/L) and none had iron deficiency anaemia. Median SF was lower in newborns whose mothers consumed greater than or equal to 3 servings of milk/day during the pregnancy (131 vs. 151 mcg/L, P=0.04). No other associations with SF or Hb were observed. CONCLUSION: Iron deficiency is present in 7% of newborns in New Zealand. Newborns whose mothers consumed more milk during pregnancy had a lower median SF concentration.
Assuntos
Anemia Ferropriva/etiologia , Ferritinas/sangue , Sangue Fetal/metabolismo , Hemoglobinas/metabolismo , Adulto , Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Animais , Biomarcadores/sangue , Estudos de Coortes , Dieta/efeitos adversos , Inquéritos sobre Dietas , Feminino , Nível de Saúde , Humanos , Recém-Nascido , Masculino , Leite/efeitos adversos , Nova Zelândia , Gravidez , Complicações na Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , Fatores de RiscoRESUMO
INTRODUCTION: Prothrombin complex concentrates (PCCs) are used for the urgent reversal of oral vitamin K antagonists in patients with life-threatening bleeding or prior to urgent procedures/surgery. PCCs offer rapid and complete reversal without the disadvantages of volume overload and adverse reactions seen with fresh frozen plasma (FFP). There is concern about the risk of thrombosis associated with the use PCCs; data on this is limited at present. OBJECTIVES: To determine the incidence of objectively confirmed arterial or venous thromboembolism within 30 days following the administration of PROTHROMBINEX®-VF (PTX-VF) to acutely reverse a prolonged INR. MATERIALS/METHODS: A prospective observational study was conducted at two teaching hospitals in Auckland, NZ. All patients who received PTX-VF for the acute reversal of prolonged INR were eligible. Baseline patient demographics and reasons for PTX-VF administration were recorded. Patients were reviewed at days 7 and 30, to confirm/exclude thromboembolism or adverse events. RESULTS: 173 patients were enrolled from August 2008 to March 2009. The most frequent indication for reversal was acute bleeding. At 30 days 4.6% (8/173) patients had a definite/probable thrombotic event, and 16.7% had died either due to the presenting bleed (intracranial haemorrhage) or a complication of their presenting complaint (e.g. sepsis, renal failure). CONCLUSIONS: Acute reversal of anticoagulant therapy with PTX-VF is associated with a significant rate of thromboembolism (4.6%) within 30 days. These events can be explained by ongoing cessation of anticoagulant therapy in patients with ongoing risk factors for arterial or venous thrombosis, rather than directly attributable to PTX-VF therapy.