RESUMEN
Background: Leukemia imposes a large healthcare burden both in China and the United States (US). The disease burden differs greatly between the two countries, but related research is limited. We explored the differences in leukemia incidence and mortality between China and the US. Methods: Data on leukemia in China and the US from 1990 to 2021 were collected from the Global Burden of Disease 2021 database. Incidence and mortality were used to estimate the disease burden, and joinpoint regression was performed to compare their secular trends. We used an age-period-cohort model to analyze the effects of age, period, and birth cohort and project future trends in the next 15 years. Results: In 2021, the age-standardized incidence rate (ASIR) and the age-standardized death rate (ASDR) of leukemia were lower in China than in the US. However, the incidence and mortality of acute lymphoblastic leukemia (ALL) was considerably higher in China. In the past decades, the ASIR showed decreased tendency in the US, while ASIR showed stable in China. The ASDR tended to decrease in both countries from 1990 to 2021. Males have higher rates of incidence and mortality than females in two countries. The age effects showed that children and older individuals have higher RRs for incidence and mortality in China, while the RRs for incidence and mortality in the US particularly increased in the older population. The disease burden of leukemia in children is obviously greater in China. The ASIRs and ASDRs of leukemia will continue to decline in the next 15 years in China and the US, with the US experiencing a more obvious downtrend. Conclusions: Over the past decades, the ASDRs in two countries both tended to decrease. And compared to the US, China had lower leukemia incidence and mortality, However, the ASIRs in China tended toward stable, which it was showed downtrend in the US. Children have obviously greater RRs for incidence and mortality in China. The incidence and mortality will decrease continuously in two countries. Effective intervention measures are needed to reduce the burden of leukemia.
Asunto(s)
Leucemia , Humanos , China/epidemiología , Estados Unidos/epidemiología , Masculino , Femenino , Leucemia/epidemiología , Leucemia/mortalidad , Adolescente , Incidencia , Persona de Mediana Edad , Adulto , Niño , Preescolar , Anciano , Lactante , Adulto Joven , Predicción , Recién Nacido , Mortalidad/tendencias , Anciano de 80 o más AñosRESUMEN
OBJECTIVES: 1,3-Butadiene (BD) exposure's link to leukemia is under regulatory scrutiny. The assessment methods for BD exposure risks have evolved from early animal and limited human studies to advanced exposure-response modelling with comprehensive quantitative data. The objec- tive of this study is to explore the nuances of exposure-response modelling, investigating how various statistical methods have influenced the quan- tification of exposure-response relationships. MATERIAL AND METHODS: Although this study was not conducted as a formal systematic review, a search was performed in Medline/Pubmed to identify all human studies on leukemia risk assessment for BD exposure. This search included articles written in English. The electronic search spanned from inception of records until July 23, 2023, using the search term: "butadiene AND (leukaemia OR leukemia OR myeloid OR lymphoid)" and was restricted to human species. Focusing on the synthetic styrene-butadiene rubber (SBR) industry cohort study conducted by the University of Alabama at Birmingham, USA, this review evaluates various statistical models and factors influenc- ing exposure-response modelling. RESULTS: Peak exposures to BD may be more influential in the dose-response relationship than cumulative or long-term exposure. The authors recommend utilizing ß-coefficients derived from the latest SBR study update, employing Cox proportional hazard modelling, non-lagged and non-transformed cumulative BD exposure, and adjusting for age and peak BD exposure. The study reveals that statistical model selection has a limited impact on the calculated dose-response effects. The significant variation in estimated cancer mortality values arises from additional assumptions needed for metrics like the excess leukemia risk or the occupational BD effective concentration. CONCLUSIONS: In con- clusion, this study provides insights into exposure-response modelling for BD exposure and leukemia mortality, highlighting the importance of peak exposures. The recommended statistical approach offers a reliable basis for regulatory risk assessment and public health population metrics. Int J Occup Med Environ Health. 2024;37(3):300-10.
Asunto(s)
Butadienos , Leucemia , Exposición Profesional , Humanos , Leucemia/inducido químicamente , Leucemia/epidemiología , Leucemia/mortalidad , Exposición Profesional/efectos adversos , Medición de Riesgo/métodos , Elastómeros , Estirenos , Relación Dosis-Respuesta a DrogaRESUMEN
Background: Leukaemia is a devastating disease with an incidence that progressively increases with advancing age. The World Health Organization has designated 2021-30 as the decade of healthy ageing, highlighting the need to address age-related diseases. We estimated the disease burden of leukaemia and forecasted it by 2030. Methods: Based on the Global Burden of Disease 2019 database, we systematically analysed the geographical distribution of leukaemia and its subtypes. We used Joinpoint regression and Bayesian age-period-cohort models to evaluate incidence and mortality trends from 1990 to 2019 and projections through 2030. We analysed five leukaemia subtypes and the impact of age, gender, and social development. Decomposition analysis revealed the effects of disease burden on ageing and population growth. We used frontier analysis to illustrate the potential of each country to reduce its burden based on its development levels. Results: Globally, the absolute numbers of leukaemia incidence and mortality have increased, while the age-standardised rates (ASRs) have shown a decreasing trend. The disease burden was more pronounced in men, the elderly, and regions with a high socio-demographic index (SDI), where ageing and population growth played varying roles across subtypes. From 2000 to 2006, disease burdens were most effectively controlled. Global ASRs of incidence might stabilise, while ASRs of death are expected to decrease until 2030. Frontier analysis showed that middle and high-middle SDI countries have the most improvement potential. Smoking and high body mass index were the main risk factors for leukaemia-related mortality and disability-adjusted life years. Conclusions: The absolute number of leukaemia cases has increased worldwide, but there has been a sharp decline in ASRs over the past decade, primarily driven by population growth and ageing. Countries with middle and high-middle SDI urgently need to take action to address this challenge.
Asunto(s)
Carga Global de Enfermedades , Leucemia , Humanos , Leucemia/epidemiología , Leucemia/mortalidad , Carga Global de Enfermedades/tendencias , Masculino , Femenino , Factores de Riesgo , Persona de Mediana Edad , Anciano , Adulto , Incidencia , Adolescente , Adulto Joven , Preescolar , Salud Global/estadística & datos numéricos , Niño , Predicción , Lactante , Anciano de 80 o más Años , Recién NacidoRESUMEN
Objective: To analyze the causes and demographic characteristics of pre-engraftment mortality in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and investigate the risk factors and measures for preventing pre-engraftment mortality. Methods: A retrospective case analysis, involving a total of 7 427 patients who underwent allo-HSCT at Peking University People's Hospital between January 2016 and July 2023, was conducted. Results: Among the 7 427 patients who underwent allo-HSCT, 56 cases (0.75% ) experienced pre-engraftment mortality. The median time to death for these 56 patients was +7 (-3 to +38) days after stem cell infusion. The median times to death for patients with acute leukemia (AL), severe aplastic anemia (SAA), and myelodysplastic syndrome (MDS) were +11 (-1 to +38), +3 (-1 to +34), and +16 (-1 to +38) days, respectively (P=0.013). The main causes of pre-engraftment mortality were infection (39.3% ), cardiac toxicity (28.6% ), and intracranial hemorrhage (26.8% ). Infection was the most common cause of pre-engraftment mortality in patients with AL and MDS (55.0% and 60.0% ), whereas cardiac toxicity was predominantly observed in patients with SAA (71.4% ), with no cases in patients with AL and only one case in patients with MDS. Among patients who died from intracranial hemorrhage, 53.3% had severe infections. The median times to death for infection, cardiac toxicity, and intracranial hemorrhage was +11 (-1 to +38), +2.5 (-1 to +17), and +8 (-3 to +37) days, respectively (P<0.001) . Conclusions: Infection is the primary cause of pre-engraftment mortality in allo-HSCT, and severe cardiac toxicity leading to pre-engraftment mortality should be closely monitored in patients with SAA.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Estudios Retrospectivos , Factores de Riesgo , Síndromes Mielodisplásicos/terapia , Anemia Aplásica/terapia , Enfermedad Injerto contra Huésped/etiología , Masculino , Femenino , Persona de Mediana Edad , Leucemia/terapia , Leucemia/mortalidad , AdultoRESUMEN
This study assessed the effect of serum magnesium levels and their role in the outcome of allogeneic hematopoietic cell transplantation (allo-HSCT) in acute leukemia. Fifty-four patients with acute leukemia who underwent allo-HSCT were divided into two groups according to their serum magnesium levels before transplantation. The results showed that serum magnesium level is an independent factor influencing the prognosis of patients undergoing allo-HSCT. Low magnesium levels were associated with inferior overall survival and event-free survival compared with the associations of high magnesium levels (HR = 0.149; (95% CI: 0.029-0.755 for overall survival; HR = 0.369; 95% CI: 0.144-0.949, p = 0.039 for event-free survival). The competing risk model showed that the cumulative incidence of acute graft-versus-host disease was significantly low in the high magnesium group (p = 0.028). In general, there is a correlation between high magnesium levels and superior outcomes, including less and milder acute graft-versus-host disease, which does not affect cyclosporine-A levels. These findings provide valuable information for identifying the risk of poor prognosis in patients preparing for transplantation.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Magnesio , Trasplante Homólogo , Humanos , Magnesio/sangre , Femenino , Masculino , Adulto , Persona de Mediana Edad , Adolescente , Pronóstico , Adulto Joven , Enfermedad Aguda , Resultado del Tratamiento , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Ciclosporina/uso terapéutico , Leucemia/terapia , Leucemia/mortalidadRESUMEN
BACKGROUND: Childhood leukemia (CL) is a major global concern, accounting for 33% of all new cancer cases and 31% of all cancer deaths in children aged 0-14 years. Our study aimed to analyze the global incidence and mortality rates of CL in 2020 and its relationship with the Human Development Index (HDI). MATERIAL AND METHODS: In this ecologic study, we analyzed the 2020 cancer incidence and mortality data for children aged 0-14 years from the GLOBOCAN Project. We calculated the Age-Standardized Incidence Rate (ASIR) and Age-Standardized Mortality Rate (ASMR) of CL per 100,000 individuals. Pearson's correlation coefficient was used to examine the association between childhood leukemia ASIR, ASMR, and the HDI, with a statistical significance threshold of P<0.05. RESULTS: In 2020, there were a total of 67,008 new cases of CL worldwide, with males accounting for 57.85%. The global ASIR for CL was 3.4 per 100,000 (3.9 in males, 3 in females). Additionally, there were 25,080 CL-related deaths, with males comprising 58.86%. The overall ASMR for CL was 1.3 (1.4 in males, 1.1 in females). We found a significant positive correlation (r = 0.405, P≤0.001) between the global ASIR and ASMR for CL. There was a strong positive correlation (r = 0.770, P = 0.001) between the HDI and childhood leukemia ASIR, but no significant association (r = 0.077, P = 0.337) was observed with ASMR. CONCLUSION: Our study reveals that CL remains a significant health burden worldwide. We identified a positive correlation between the ASIR of CL and the HDI, indicating a potential role of socioeconomic factors in CL incidence.
Asunto(s)
Salud Global , Leucemia , Humanos , Niño , Lactante , Masculino , Preescolar , Femenino , Incidencia , Adolescente , Leucemia/epidemiología , Leucemia/mortalidad , Recién Nacido , Salud Global/estadística & datos numéricosRESUMEN
Leukemia is associated with exposure to radiation, benzene derivatives, and pesticides. Previous research has documented an increase in work-related leukemia in the Latin American Andean region. To date, there are only few studies in Ecuador on the impact of oil exploitation on adjacent indigenous communities. Our study aims to show the impact of leukemia on the working-age population. For the calculation of morbidity and mortality rates, we used hospital discharge and death records from the National Institute of Statistics of Ecuador. These data were collected and adjusted to the corresponding province's population for further analysis. Large differences were observed between provinces in adjusted rates of leukemia mortality and morbidity in the working-age population. The variations in altitude among different areas in Ecuador give the provinces a distinct geographic identity. Likewise, the provinces with the highest morbidity and mortality rankings, such as Azuay, Loja, Imbabura, and Tungurahua, have an average altitude above 2000 meters. As a result, there are variations in the average temperature, exposure to solar and cosmic radiation, and mining and farming methods. The observed differences warrant the future collection of geolocation data for affected individuals. This could help to better understand how leukemia cases have demogrpahic hotspots in the country, identify possible risk factors associated with the disease in each region, and design more effective prevention and control strategies.
La leucemia es una enfermedad a consecuencia, además de factores genéticos, de la exposición a radiaciones, derivados del benceno y pesticidas. Investigaciones anteriores han documentado un aumento de la leucemia ocupacional en la región andina de América Latina. Hasta la fecha, existen sólo unos pocos estudios en Ecuador sobre el impacto de la explotación petrolera en las comunidades indígenas. Nuestro objetivo es mostrar el impacto de la leucemia en la población en edad de trabajar. Para el cálculo de las tasas de morbimortalidad se utilizaron los registros de altas hospitalarias y defunciones del Instituto Nacional de Estadística del Ecuador. Estos datos fueron recopilados y estimadas las tasas ajustadas. Se observaron grandes diferencias entre provincias en las tasas ajustadas de mortalidad y morbilidad por leucemia en la población en edad de trabajar. Asimismo, las provincias con mayor ranking de morbilidad y mortalidad, como Azuay, Loja, Imbabura y Tungurahua, coinciden en tener una altitud promedio superior a los 2000 metros. Hay provincias de baja altitud en la costa y provincias por encima de los 2000 metros en la sierra, lo que le da a las provincias del Ecuador una identidad geográfica distintiva. Como resultado, existen variaciones en la temperatura promedio, la exposición a la radiación solar y cósmica, y actividades de minería y agricultura. Las diferencias observadas, recomiendan la recopilación futura de datos de geolocalización de las personas afectadas. Esto podría ayudarnos a comprender mejor cómo se distribuyen los casos de leucemia, identificar posibles factores de riesgo asociados a la enfermedad en cada región y diseñar estrategias de prevención y control más efectivas.
Asunto(s)
Leucemia , Humanos , Ecuador/epidemiología , Leucemia/epidemiología , Leucemia/mortalidad , Leucemia/etiología , Adulto , Factores de Riesgo , Persona de Mediana Edad , Masculino , Femenino , Altitud , Adulto Joven , Exposición a Riesgos Ambientales/efectos adversos , Adolescente , Exposición Profesional/efectos adversosRESUMEN
BACKGROUND: Leukemia is the most common childhood malignancy. Identifying prognostic factors of patient survival and relapse using more reliable statistical models instead of traditional variable selection methods such as stepwise regression is of great importance. The present study aimed to apply a penalized semi-parametric mixture cure model to identify the prognostic factors affecting short-term and long-term survival of childhood leukemia in the presence of competing risks. The outcome of interest in this study was time to relapse. Study Design: A retrospective cohort study. METHODS: A total of 178 patients (0â15 years old) with leukemia participated in this study (September 1997 to September 2016, followed up to June 2021) at Golestan University of Medical Sciences, Iran. Demographic, clinical, and laboratory data were collected, and then a penalized semi-parametric mixture cure competing risk model with smoothly clipped absolute deviation (SCAD) and least absolute shrinkage and selection operator (LASSO) regularizations was used to analyze the data. RESULTS: Important prognostic factors of relapse patients selected by the SCAD regularization method were platelets (150000â400000 vs.>400000; odds ratio=0.31) in the cure part and type of leukemia (ALL vs. AML, hazard ratio (HR)=0.08), mediastinal tumor (yes vs. no, HR=16.28), splenomegaly (yes vs. no; HR=2.94), in the latency part. In addition, significant prognostic factors of death identified by the SCAD regularization method included white blood cells (<4000 vs.>11000, HR=0.25) and rheumatoid arthritis signs (yes vs. no, HR=5.75) in the latency part. CONCLUSION: Several laboratory factors and clinical side effects were associated with relapse and death, which can be beneficial in treating the disease and predicting relapse and death time.
Asunto(s)
Recurrencia , Humanos , Niño , Masculino , Femenino , Estudios Retrospectivos , Preescolar , Factores de Riesgo , Adolescente , Lactante , Pronóstico , Irán/epidemiología , Leucemia/mortalidad , Leucemia/terapia , Recién Nacido , Modelos Estadísticos , Leucemia Mieloide Aguda/mortalidad , Modelos de Riesgos Proporcionales , Recurrencia Local de Neoplasia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Recuento de PlaquetasRESUMEN
BACKGROUND: The incidence of childhood malnutrition i.e., both obesity and undernutrition, is on a rise. While there is extensive evidence of the influence of body mass index (BMI) on the survival and other important outcomes of adult cancers, the impact of childhood BMI on one of the common pediatric cancers i.e., leukemia is not well studied. METHODS: Systematic search of PubMed, Scopus, and Google Scholar databases was done to identify studies that were conducted among pediatric patients with leukemia and had examined outcomes of interest based on BMI at the time of diagnosis. RESULTS: Effect sizes were reported as pooled hazards ratio (HR) along with 95% confidence intervals (CI). A total of 17 studies were included. Compared to pediatric leukemia patients with normal BMI, underweight (HR 1.07, 95% CI: 1.04, 1.11) and obese (HR 1.42, 95% CI: 1.18, 1.71) children with leukemia had higher risks of overall mortality. Underweight (HR 1.10, 95% CI: 1.02, 1.19) and obese (HR 1.34, 95% CI: 1.15, 1.55) pediatric leukemia patients had a tendency to lower event-free survival compared to children with normal BMI. The risk of relapse was not significant for underweight, overweight, and obese children. CONCLUSIONS: Both underweight and obese status at the time of diagnosis were associated with poor survival outcomes in pediatric patients with leukemia.
Asunto(s)
Índice de Masa Corporal , Humanos , Niño , Leucemia/diagnóstico , Leucemia/mortalidad , Leucemia/complicaciones , Delgadez/complicaciones , Obesidad/complicaciones , PreescolarRESUMEN
BACKGROUND AND AIMS: Umbilical cord blood transplantation (UCBT) has emerged as a promising treatment option for patients with acute leukemia needing hematopoietic stem cell transplantation. Both single (sUCBT) and double cord blood units (dUCBT) demonstrate potential benefits, but studies comparing their effectiveness have shown mixed results. This meta-analysis aimed to determine the comparative safety and efficacy of sUCBT versus dUCBT in acute leukemia patients. METHODS: Electronic databases were systematically examined to identify relevant studies comparing single vs double UCBT published until November 2023. Nine studies involving 3864 acute leukemia patients undergoing UCBT were included. Outcomes analyzed were acute graft-versus-host disease (GVHD), chronic GVHD, relapse, non-relapse mortality, leukemia-free survival and overall survival. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random effects model. RESULTS: The risk of Grade II-IV acute GVHD (RR 1.55, 95% CI 1.19-2.03) and Grade III-IV acute GVHD (RR 1.25, 95% CI 1.07-1.46) were significantly higher with dUCBT. Relapse risk was lower with dUCBT (RR 0.57, 95% CI 0.38-0.88) while overall survival favored sUCBT (RR 1.25, 95% CI 1.06-1.46). No significant differences were observed for chronic GVHD, non-relapse mortality or leukemia-free survival. CONCLUSION: Both single and double UCBT have potential as effective treatments for acute leukemia. The choice of treatment should consider various factors, including the risk of GVHD, relapse, and mortality. More research, especially randomized trials, is needed to provide definitive guidance on the optimal use of single and double unit UCBT in patients with acute leukemia.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Humanos , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Leucemia/terapia , Leucemia/mortalidad , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Enfermedad AgudaRESUMEN
BACKGROUND: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. Whether the integration of CAR T-cell therapy and allogeneic HSCT can preserve CAR T-cell function and improve tumor control is unclear. METHODS: We tested a novel "all-in-one" strategy consisting of sequential CD7 CAR T-cell therapy and haploidentical HSCT in 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma. After CAR T-cell therapy led to complete remission with incomplete hematologic recovery, patients received haploidentical HSCT without pharmacologic myeloablation or GVHD prophylaxis drugs. Toxic effects and efficacy were closely monitored. RESULTS: After CAR T-cell therapy, all 10 patients had complete remission with incomplete hematologic recovery and grade 4 pancytopenia. After haploidentical HSCT, 1 patient died on day 13 of septic shock and encephalitis, 8 patients had full donor chimerism, and 1 patient had autologous hematopoiesis. Three patients had grade 2 HSCT-associated acute GVHD. The median follow-up was 15.1 months (range, 3.1 to 24.0) after CAR T-cell therapy. Six patients remained in minimal residual disease-negative complete remission, 2 had a relapse of CD7-negative leukemia, and 1 died of septic shock at 3.7 months. The estimated 1-year overall survival was 68% (95% confidence interval [CI], 43 to 100), and the estimated 1-year disease-free survival was 54% (95% CI, 29 to 100). CONCLUSIONS: Our findings suggest that sequential CD7 CAR T-cell therapy and haploidentical HSCT is safe and effective, with remission and serious but reversible adverse events. This strategy offers a feasible approach for patients with CD7-positive tumors who are ineligible for conventional allogeneic HSCT. (Funded by the National Natural Science Foundation of China and the Key Project of Science and Technology Department of Zhejiang Province; ClinicalTrials.gov numbers, NCT04599556 and NCT04538599.).
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Inmunoterapia Adoptiva , Leucemia , Linfoma , Receptores Quiméricos de Antígenos , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Antígenos CD7 , Terapia Combinada , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Leucemia/terapia , Leucemia/mortalidad , Linfoma/mortalidad , Linfoma/terapia , Receptores Quiméricos de Antígenos/uso terapéutico , Inducción de Remisión , Trasplante Homólogo , Recurrencia , AncianoRESUMEN
Cytomegalovirus (CMV) reactivation increases treatment-related mortality (TRM) after allogeneic hematopoietic cell transplantation (allo-HCT). We analyzed 141 adult acute leukemia (AL) patients suffered allo-HCT between 2017 and 2021, who developed CMV viremia post-HCT and treated with valganciclovir or foscarnet, to evaluate effectiveness and safety of both drugs. Viremia clearance rates (14 and 21 d post treatment) and toxicities were similar in two groups. However, valganciclovir was associated with a lower cumulative incidence of CMV recurrence within 180 days (16.7% vs. 35.7%, p=0.029) post CMV clearance. Finally, 2-year TRM was lower in valganciclovir group (9.7% ± 0.2% vs. 26.2% ± 0.3%, p = 0.026), result a superior 2-year overall survival (OS; 88.1% ± 5.2% vs. 64.4% ± 5.5%, p = 0.005) and leukemia-free survival (LFS; 82.0% ± 5.9% vs. 58.9% ± 5.6%, p = 0.009). Valganciclovir might decrease CMV viremia recurrence and led to better long-term outcome than foscarnet in adult AL patients developed CMV viremia post-HCT. Considering the inherent biases of retrospective study, well-designed trials are warranted to validate our conclusion.
Asunto(s)
Antivirales , Infecciones por Citomegalovirus , Citomegalovirus , Foscarnet , Trasplante de Células Madre Hematopoyéticas , Trasplante Homólogo , Valganciclovir , Viremia , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones por Citomegalovirus/etiología , Valganciclovir/uso terapéutico , Masculino , Femenino , Viremia/tratamiento farmacológico , Adulto , Antivirales/uso terapéutico , Foscarnet/uso terapéutico , Persona de Mediana Edad , Citomegalovirus/efectos de los fármacos , Estudios Retrospectivos , Adulto Joven , Anciano , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/mortalidad , Resultado del Tratamiento , Leucemia/terapia , Leucemia/complicaciones , Leucemia/mortalidadRESUMEN
OBJECTIVE: To assess the magnitude, trend, and spatial patterns of childhood and adolescent cancer mortality between 1996 and 2017 in 133 Brazilian intermediate regions by using socioeconomic and healthcare services indicators. METHODS: This is an ecological study for analyzing the trend of mortality from cancer in childhood and adolescence through time series. Data on deaths were extracted from the Brazilian Mortality Information System. Data on population were extracted from the 1991, 2000, and 2010 demographic censuses of the Brazilian Institute of Geography and Statistics, with interpolation for intercensal years. Time series were delineated for mortality by type of cancer in each intermediate region. Such regions were grouped by macroregions to present the results. The calculation and interpretation of mortality trends use the Prais-Winsten autoregression procedure. RESULTS: Mortality rates for all neoplasms were higher in the Northern region (7.79 deaths per 100 thousand population), while for leukemias, they were higher in the Southern region (1.61 deaths per 100 thousand population). In both regions, mortality was higher in boys and in the 0-4 age group. The trend was decreasing (annual percent change [APC] - -2.11 [95%CI: -3.14; - 1.30]) for all neoplasms in the Brazilian regions and stationary (APC - -0.43 [95%CI: -1.61; 2.12]) for leukemias in the analyzed period. CONCLUSION: The mortality rate for all neoplasms showed higher values in regions with smaller numbers of ICU beds in the public healthcare system.
Asunto(s)
Leucemia , Neoplasias , Adolescente , Humanos , Masculino , Brasil/epidemiología , Atención a la Salud , Geografía , Leucemia/mortalidad , Mortalidad/tendencias , Neoplasias/mortalidadRESUMEN
BACKGROUND: Leukemia is a threat to human health, and there are relatively few studies on the incidence, mortality and disease burden analysis of leukemia in China. This study aimed to analyze the incidence and mortality rates of leukemia in China from 2005 to 2017 and estimate their age-period-cohort effects, it is an important prerequisite for effective prevention and control of leukemia. METHODS: Leukemia incidence and mortality data from 2005 to 2017 were collected from the Chinese Cancer Registry Annual Report. Joinpoint regression model was used to estimate the average annual percentage change (AAPC) and annual percentage change (APC) response time trend. Age-period-cohort model was constructed to analyze the effects of age, period and cohort. RESULTS: The age-standardized incidence rate of leukemia was 4.54/100,000 from 2005 to 2017, showed an increasing trend with AAPC of 1.9% (95% CI: 1.3%, 2.5%). The age-standardized mortality rate was 2.91/100,000, showed an increasing trend from 2005 to 2012 with APC of 2.1% (95%CI: 0.4%, 3.9%) and then a decreasing trend from 2012 to 2017 with APC of -2.5% (95%CI: -5.3%, 0.3%). The age-standardized incidence (mortality) rates of leukemia were not only higher in males than that in females, but also increased more rapidly. The incidence of leukemia in rural areas was lower than in urban areas, but the AAPC was 2.2 times higher than urban areas. Children aged 0-4 years were at higher risk of leukemia. The risk of leukemia incidence and mortality increased with age. The period effect of leukemia mortality risk showed a decreasing trend, while the cohort effect showed an increasing and then decreasing trend with the turning point of 1955-1959. CONCLUSIONS: The age-standardized incidence rate of leukemia in China showed an increasing trend from 2005 to 2017, while the age-standardized mortality rate increased first and then decreased in 2012 as a turning point. Differences existed by gender and region. The risk of leukemia incidence and mortality increased accordingly with age. The risk of mortality due to leukemia gradually decreased from 2005 to 2017. Leukemia remains a public health problem that requires continuous attention.
Asunto(s)
Leucemia , Femenino , Humanos , Masculino , China/epidemiología , Leucemia/epidemiología , Leucemia/mortalidad , Modelos Lineales , Salud PúblicaRESUMEN
Scedosporium and Lomentospora species are environmental moulds that are virulent in immunocompromised hosts and rarely cause bloodstream infection (BSI). Patients with Scedosporium and Lomentospora species BSI were identified by the state public laboratory service in Queensland, Australia, over a 20-year period. Twenty-two incident episodes occurred among 21 residents; one patient had a second episode 321 days following the first. Of these, 18 were Lomentospora prolificans, three were Scedosporium apiospermum complex and one was a nonspeciated Scedosporium species. Seventeen (81%) patients died during their index admission, and all-cause mortality at 30, 90 and 365 days was 73%, 82% and 91% respectively. All 20 patients with haematological malignancy died within 365 days of follow-up with a median time to death of 9 days (interquartile range, 6-20 days) following diagnoses of BSI.
Asunto(s)
Fungemia , Huésped Inmunocomprometido , Leucemia , Scedosporium , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Australia/epidemiología , Fungemia/diagnóstico , Fungemia/epidemiología , Fungemia/microbiología , Fungemia/mortalidad , Leucemia/epidemiología , Leucemia/mortalidad , Scedosporium/aislamiento & purificación , Scedosporium/patogenicidadRESUMEN
To avoid graft rejection, the hematopoietic stem cells with matched classical human leukocyte antigen (HLA) alleles are the primary choice for clinical allogeneic transplantation. However, even if the fully HLA-matched hematopoietic stem cells are used for transplantation, some patients still have poor prognosis after hematopoietic stem cell transplantation (HSCT), suggesting that the HLA system was not the only determinant of the outcomes of HSCT. In this study, we investigated whether the single-nucleotide polymorphisms (SNPs) of the co-stimulatory genes within non-HLA regions were related to the outcomes of HSCT. The genomic DNAs of 163 patients who had acute leukemia and received HSCT and their respective donors were collected for analysis. Thirty-four SNPs located in the four co-stimulatory genes including cytotoxic T-lymphocyte associated protein 4 (CTLA4), CD28, tumor necrosis factor ligand superfamily 4 (TNFSF4), and programmed cell death protein 1 (PDCD1) were selected to explore their relationship with the adverse outcomes after transplantation, including mortality, cytomegalovirus infection, graft-versus-host disease, and relapse. Our results revealed that nine SNPs in the CTLA4 gene, five SNPs in the PDCD1 gene, two SNPs in the TNFSF4 gene, and four SNPs in the CD28 gene were significantly associated with the occurrence of adverse outcomes post-HSCT. These SNPs may play important roles in immune response to allografts post-HSCT and can be the targets for developing strategy to identify appropriate donors.
Asunto(s)
Antígenos CD28/genética , Antígeno CTLA-4/genética , Antígenos HLA/inmunología , Trasplante de Células Madre Hematopoyéticas , Leucemia/cirugía , Ligando OX40/genética , Polimorfismo de Nucleótido Simple , Receptor de Muerte Celular Programada 1/genética , Adolescente , Adulto , Anciano , Antígenos CD28/inmunología , Antígeno CTLA-4/inmunología , Niño , Preescolar , Infecciones por Citomegalovirus/genética , Infecciones por Citomegalovirus/inmunología , Selección de Donante , Femenino , Enfermedad Injerto contra Huésped/genética , Enfermedad Injerto contra Huésped/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Lactante , Leucemia/genética , Leucemia/inmunología , Leucemia/mortalidad , Masculino , Persona de Mediana Edad , Ligando OX40/inmunología , Receptor de Muerte Celular Programada 1/inmunología , Recurrencia , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Although approximately 70% of pediatric hematological malignancies are curable, approximately 30% remain fatal. No standard treatment is available in patients showing relapse and those with refractory disease. Although different methods are adopted in different hospitals, its efficacy is extremely limited. In recent years, haploidentical stem cell transplantation, involving high-dose cyclophosphamide administration post-transplanta tion, has been used, mainly in adults; however, its application is limited to removal of alloreactive T cells. Multicenter single-arm clinical trials of T-cell replete haploidentical stem cell transplantation (TCR-haplo-SCT) will be conducted in children with relapsed and refractory acute leukemia. After myeloablative conditioning using total body irradiation or busulfan, intensive graft versus host disease prophylaxis is administered, consisting of low-dose rabbit anti-human thymocyte globulin, tacrolimus, methotrexate, and prednisolone. An external control group is set up for the study. The treatment period is around 3 months, and the follow-up period is 2 years from transplantation completion.The aim of this study is to verify the efficacy and safety of TCR-haplo-SCT and present it as a new immune cell therapy for improving survival rate in children with relapsed and refractory acute leukemia.
Asunto(s)
Suero Antilinfocítico/administración & dosificación , Leucemia/terapia , Trasplante de Células Madre , Linfocitos T/trasplante , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Adolescente , Suero Antilinfocítico/uso terapéutico , Niño , Femenino , Haplotipos , Humanos , Factores Inmunológicos , Inmunosupresores/uso terapéutico , Leucemia/mortalidad , Masculino , Receptores de Antígenos de Linfocitos T , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Cholesterol plays vital roles in human physiology; abnormal levels have deleterious pathological consequences. In cancer, elevated or reduced expression of cholesterol biosynthesis is associated with good or poor prognosis, but the underlying mechanisms are largely unknown. The limonoid compounds A1542 and A1543 stimulate ERK/MAPK by direct binding, leading to leukemic cell death and suppression of leukemia in mouse models. In this study, we investigated the downstream consequences of these ERK/MAPK agonists in leukemic cells. METHODS: We employed RNAseq analysis combined with Q-RT-PCR, western blot and bioinformatics to identify and confirm genes whose expression was altered by A1542 and A1543 in leukemic cells. ShRNA lentiviruses were used to silence gene expression. Cell culture and an animal model (BALB/c) of erythroleukemia induced by Friend virus were utilized to validate effects of cholesterol on leukemia progression. RESULTS: RNAseq analysis of A1542-treated cells revealed the induction of all 18 genes implicated in cholesterol biosynthesis. Expression of these cholesterol genes was blocked by cedrelone, an ERK inhibitor. The cholesterol inhibitor lovastatin diminished ERK/MAPK activation by A1542, thereby reducing leukemic cell death induced by this ERK1/2 agonist. Growth inhibition by cholesterol was observed both at the intracellular level, and when orally administrated into a leukemic mouse model. Both HDL and LDL also suppressed leukemogenesis, implicating these lipids as important prognostic markers for leukemia progression. Mechanistically, knockdown experiments revealed that the activation of SREBP1/2 by A1542-A1543 was responsible for induction of only a sub-set of cholesterol biosynthesis genes. Induction of other regulatory factors by A1542-A1543 including EGR1, AP1 (FOS + JUN) LDLR, IER2 and others may cooperate with SREBP1/2 to induce cholesterol genes. Indeed, pharmacological inhibition of AP1 significantly inhibited cholesterol gene expression induced by A1542. In addition to leukemia, high expression of cholesterol biosynthesis genes was found to correlate with better prognosis in renal cancer. CONCLUSIONS: This study demonstrates that ERK1/2 agonists suppress leukemia and possibly other types of cancer through transcriptional stimulation of cholesterol biosynthesis genes.
Asunto(s)
Colesterol/metabolismo , Leucemia/genética , Limoninas/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Animales , Femenino , Humanos , Leucemia/mortalidad , Masculino , Ratones , Transducción de Señal , Análisis de Supervivencia , TransfecciónRESUMEN
Transplantation of allogeneic hematopoietic cells faces two barriers: failure of engraftment due to a host versus graft reaction, and the attack of donor cells against the patient, the graft versus host (GVH) reaction. This reaction may lead to GVH disease (GVHD), but in patients transplanted due to leukemia or other malignant disorders, this may also convey the benefit of a graft versus leukemia (GVL) effect. The interplay of transplant conditioning with donor and host cells and the environment in the patient is complex. The microbiome, particularly in the intestinal tract, profoundly affects these interactions, directly and via soluble mediators, which also reach other host organs. The microenvironment is further altered by the modifying effect of malignant cells on marrow niches, favoring the propagation of the malignant cells. The development of stable mixed donor/host chimerism has the potential of GVHD prevention without necessarily increasing the risk of relapse. There has been remarkable progress with novel conditioning regimens and selective T-cell manipulation aimed at securing engraftment while preventing GVHD without ablating the GVL effect. Interventions to alter the microenvironment and change the composition of the microbiome and its metabolic products may modify graft/host interactions, thereby further reducing GVHD, while enhancing the GVL effect. The result should be improved transplant outcome.