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OBJECTIVES: An increased risk of haematological malignancies (HM) has been reported in GCA patients. Our study aimed to investigate the incidence and the type of HM occurring in GCA. METHODS: All patients with GCA and HM living in Côte d'Or (France) were identified by crossing data from the RHEMCO (Registre des Hémopathies Malignes de Côte d'Or) and those having a positive temporal artery biopsy between 1 January 2001 and 31 December 2018. RESULTS: Among 276 biopsy-proven GCA patients, 14 HM were identified in 12 patients (4.3%). In comparison with the general population aged >50 y, the incidence of myeloid HM and myeloproliferative syndromes were increased in GCA patients [standardized incidence ratios (SIR) = 2.71 and 5.16, respectively], with a specific increase in men with GCA (SIR = 4.82 and 9.04, respectively) but not in women. In addition, the study of SIR depending on the chronology between GCA and HM diagnoses suggests that there was an increased risk of developing GCA in men but not in women, after a diagnosis of myeloid HM (SIR = 9.56), especially if it was a MPS (SIR = 17.56). CONCLUSIONS: Our study shows a particular epidemiology of HM in GCA patients, which is characterized by an increased incidence of myeloid HM, especially MPS, in male GCA patients. The chronology of the diagnoses of GCA and HM raises the hypothesis that clonal hematopoiesis may be implicated in some cases of GCA.
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Arteritis de Células Gigantes/complicaciones , Neoplasias Hematológicas/epidemiología , Femenino , Francia/epidemiología , Neoplasias Hematológicas/etiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Since the 1990s and since the development of humanised monoclonal antibodies in 1998, the treatment of non-Hodgkin lymphoma has undergone profound changes. Follicular lymphoma (FL) was the first to benefit from this treatment, and several clinical trials have shown a significant improvement in overall survival, but little information is available at a population level. OBJECTIVE: Our objective was to estimate changes in FL-specific mortality at a population level, with an appropriate methodology. METHODS: Two French retrospective population-based studies on FL were conducted, one from 1995 to 2004, in 1477 patients, and one from 1995 to 2010, in 451 patients. Trends in excess mortality rates (EMRs) according to age, sex, Ann Arbor stage and year of diagnosis were evaluated using the flexible model of Remontet et al. RESULTS: Trends in the EMR differed according to age at diagnosis and was higher in advanced stage (III, IV) in patients older than 65 yr. The EMR decreased linearly from 1995 to 2010. This decrease was more marked for advanced stages. CONCLUSION: FL-specific mortality decreased over the years of diagnosis, and the difference according to the lymphoma stage diminished in more recent years. However, progress in the management of FL was not able to erase age-related differences.
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Linfoma Folicular/mortalidad , Vigilancia de la Población , Adolescente , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Femenino , Francia/epidemiología , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Linfoma Folicular/diagnóstico , Linfoma Folicular/epidemiología , Linfoma Folicular/historia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Sistema de Registros , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: More effective treatments have become available for haematological malignancies from the early 2000s, but few large-scale population-based studies have investigated their effect on survival. Using EUROCARE data, and HAEMACARE morphological groupings, we aimed to estimate time trends in population-based survival for 11 lymphoid and myeloid malignancies in 20 European countries, by region and age. METHODS: In this retrospective observational study, we included patients (aged 15 years and older) diagnosed with haematological malignancies, diagnosed up to Dec 31, 2007, and followed up to Dec 31, 2008. We used data from the 30 cancer registries (across 20 countries) that provided continuous incidence and good quality data from 1992 to 2007. We used a hybrid approach to estimate age-standardised and age-specific 5-year relative survival, for each malignancy, overall and for five regions (UK, and northern, central, southern, and eastern Europe), and four 3-year periods (1997-99, 2000-02, 2003-05, 2006-08). For each malignancy, we also estimated the relative excess risk of death during the 5 years after diagnosis, by period, age, and region. FINDINGS: We analysed 560â444 cases. From 1997-99 to 2006-08 survival increased for most malignancies: the largest increases were for diffuse large B-cell lymphoma (42·0% [95% CI 40·7-43·4] to 55·4% [54·6-56·2], p<0·0001), follicular lymphoma (58·9% [57·3-60·6] to 74·3% [72·9-75·5], p<0·0001), chronic myeloid leukaemia (32·3% [30·6-33·9] to 54·4% [52·5-56·2], p<0·0001), and acute promyelocytic leukaemia (50·1% [43·7-56·2] to 61·9% [57·0-66·4], p=0·0038, estimate not age-standardised). Other survival increases were seen for Hodgkin's lymphoma (75·1% [74·1-76·0] to 79·3% [78·4-80·1], p<0·0001), chronic lymphocytic leukaemia/small lymphocytic lymphoma (66·1% [65·1-67·1] to 69·0% [68·1-69·8], p<0·0001), multiple myeloma/plasmacytoma (29·8% [29·0-30·6] to 39·6% [38·8-40·3], p<0·0001), precursor lymphoblastic leukaemia/lymphoma (29·8% [27·7-32·0] to 41·1% [39·0-43·1], p<0·0001), acute myeloid leukaemia (excluding acute promyelocytic leukaemia, 12·6% [11·9-13·3] to 14·8% [14·2-15·4], p<0·0001), and other myeloproliferative neoplasms (excluding chronic myeloid leukaemia, 70·3% [68·7-71·8] to 74·9% [73·8-75·9], p<0·0001). Survival increased slightly in southern Europe, more in the UK, and conspicuously in northern, central, and eastern Europe. However, eastern European survival was lower than that for other regions. Survival decreased with advancing age, and increased with time only slightly in patients aged 75 years or older, although a 10% increase in survival occurred in elderly patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic myeloid leukaemia. INTERPRETATION: These trends are encouraging. Widespread use of new and more effective treatment probably explains much of the increased survival. However, the persistent differences in survival across Europe suggest variations in the quality of care and availability of the new treatments. High-resolution studies that collect data about stage at diagnosis and treatments for representative samples of cases could provide further evidence of treatment effectiveness and explain geographic variations in survival. FUNDING: Compagnia di San Paolo, Fondazione Cariplo, European Commission, and Italian Ministry of Health.
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Causas de Muerte , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Adolescente , Adulto , Anciano , Estudios de Cohortes , Terapia Combinada , Intervalos de Confianza , Supervivencia sin Enfermedad , Europa (Continente) , Femenino , Neoplasias Hematológicas/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Adulto JovenRESUMEN
BACKGROUND & AIMS: Treatment with immunosuppressive thiopurines such as azathioprine is associated with an increased risk of leukemogenesis. We assessed the risk of myeloid disorders, such as acute myeloid leukemia and myelodysplastic syndromes, in a large cohort of patients with inflammatory bowel disease (IBD) in France. METHODS: We performed a prospective observational study of 19,486 patients with IBD enrolled in the Cancers Et Surrisque Associé aux Maladies inflammatoires intestinales En France (CESAME) study from May 2004 through June 2005; patients were followed through December 31, 2007. The incidence of myeloid disorders in the general population, which was used for reference, was determined from the French Network of Cancer Registries. RESULTS: During 49,736 patient-years of follow-up, 5 patients were diagnosed with incident myeloid disorders (2 with acute myeloid leukemia and 3 with myelodysplastic syndromes). Four of these patients had been exposed to thiopurines (1 with ongoing treatment and 3 with past exposure). The risk of myeloid disorders was not increased among the overall IBD population, compared with the general population; the standardized incidence ratio (SIR) was 1.80 (95% confidence interval [CI], 0.58-4.20). The risk of myeloid disorders was not increased among patients with IBD and ongoing thiopurine treatment (SIR, 1.54; 95% CI, 0.05-8.54), but patients with past exposures to thiopurines had an increased risk of myeloid disorders (SIR, 6.98; 95% CI, 1.44-20.36). CONCLUSIONS: Past exposure to thiopurines increases the risk of myeloid disorders 7-fold among patients with IBD. This finding should be considered when initiating thiopurine therapy, so risks and benefits can be calculated.
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Azatioprina/efectos adversos , Inmunosupresores/efectos adversos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Leucemia Mieloide Aguda/epidemiología , Síndromes Mielodisplásicos/epidemiología , Adolescente , Adulto , Azatioprina/uso terapéutico , Estudios de Cohortes , Femenino , Francia/epidemiología , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Leucemia Mieloide Aguda/inducido químicamente , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/inducido químicamente , Estudios Prospectivos , Medición de Riesgo , Adulto JovenRESUMEN
BACKGROUND: In descriptive epidemiology, there are strong similarities between incidence and survival analyses. Because of the success of multidimensional penalized splines (MPSs) in incidence analysis, we propose in this pedagogical paper to show that MPSs are also very suitable for survival or net survival studies. METHODS: The use of MPSs is illustrated in cancer epidemiology in the context of survival trends studies that require specific statistical modelling. We focus on two examples (cervical and colon cancers) using survival data from the French cancer registries (cases 1990-2015). The dynamic of the excess mortality hazard according to time since diagnosis was modelled using an MPS of time since diagnosis, age at diagnosis and year of diagnosis. Multidimensional splines bring the flexibility necessary to capture any trend patterns while penalization ensures selecting only the complexities necessary to describe the data. RESULTS: For cervical cancer, the dynamic of the excess mortality hazard changed with the year of diagnosis in opposite ways according to age: this led to a net survival that improved in young women and worsened in older women. For colon cancer, regardless of age, excess mortality decreases with the year of diagnosis but this only concerns mortality at the start of follow-up. CONCLUSIONS: MPSs make it possible to describe the dynamic of the mortality hazard and how this dynamic changes with the year of diagnosis, or more generally with any covariates of interest: this gives essential epidemiological insights for interpreting results. We use the R package survPen to do this type of analysis.
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Neoplasias del Colon , Neoplasias del Cuello Uterino , Humanos , Femenino , Anciano , Análisis de Supervivencia , Modelos Estadísticos , Neoplasias del Cuello Uterino/epidemiología , Incidencia , Sistema de Registros , Tasa de SupervivenciaRESUMEN
Three hundred and twenty-seven patients from two population-based cohorts with an established diagnosis of polycythaemia vera were studied for prognostic risk factors for survival and leukaemia in a long-term survey. The relative survival (RS) was 72% and 46% at 10 and 20 years respectively, from the time of diagnosis. Multivariate analysis identified age >70 years, white blood cell count >13 × 10(9) /l and thrombo-embolism at diagnosis as independent risk factors. Patients with two or three of these factors had a 10 year RS of 26%, compared with 59% and 84% in patients with one and no risk factors, respectively. Age and leucocyte count are the main predicting factors for survival in polycythaemia vera.
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Leucocitosis/mortalidad , Policitemia Vera/mortalidad , Trombosis/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Causas de Muerte , Comorbilidad , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Francia/epidemiología , Insuficiencia Cardíaca/mortalidad , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidad , Recuento de Leucocitos , Leucocitosis/etiología , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Policitemia Vera/sangre , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Suecia/epidemiología , Trombosis/etiología , Adulto JovenRESUMEN
PURPOSE: To describe Health-Related Quality of Life (HRQoL) and to identify the association between sociodemographic, clinical and psychosocial factors, and self-reported HRQoL among NHL survivors. METHODS: The data of the cancer registry specialized in hematological malignancies in Côte d'Or (France) were used to identify all patients diagnosed with follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) from 2010 to 2017. Patients were invited to complete SF-12 and other questionnaires. RESULTS: The HRQoL of NHL survivors was poorer than that of the French general population (p < 0.05) in vitality (48 vs. 56), general health (56 vs. 63), role physical scores (60 vs. 70), role emotional scores (64 vs. 72) and the Mental Component Scale (45 vs. 49). The mean difference in physical functioning decreased per unit increase in age (ß = -1.1 (0.3); p < 0.001). Men had better vitality than women (ß = 12.4 (6.1); p = 0.04) and the high education level was associated with greater role emotional scores (ß = 14.1 (5.4); p = 0.01). Symptoms of anxiety and depression were associated with poorer HRQoL. The satisfaction of social support was associated with significantly greater scores on mental health (ß = 17.3 (5.1); p = 0.001) and social functioning (ß = 15.7 (7.8); p = 0.04). Socioeconomic deprivation was associated with poorer general health (ß = -12.8 (5.2); p = 0.01). CONCLUSIONS: From 3 to 11 years post-diagnosis, the main factors found to be associated with poor HRQoL of NHL survivors were age, sex, presence of anxiety, depression and economic problems. These findings suggest the need for supportive care to improve HRQOL and the consideration of these problems when developing care plans for NHL survivors.
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BACKGROUND: The excess mortality observed in Acute Myeloblastic Leukaemia (AML) patients, partly attributed to unequal access to curative treatments, could be linked to care pathways. METHODS: We included 1039 AML incident cases diagnosed between 2012-2016 from the 3 French blood cancer registries (3,625,400 inhabitants). We describe patients according to age, the medical entry unit and access to the specialised haematology unit (SHU) during follow-up. Multivariate logistic regression model was done to determine the association between covariables and access to SHU. A total of 713 patients (69%) had access to SHU during care. RESULTS: The most common care pathway concerned referral from the general practitioner to SHU, n = 459(44%). The univariate analysis observed a downward trend for the most deprived patients. Patients who consulted in SHU were younger (66 years vs. 83, p < 0.001), and 92% had access to cytogenetic analysis (vs. 54%, p < 0.001). They also had less poor prognosis AML-subtypes (AML-MRC, t-AML/MDS and AML-NOS) (38% vs. 69%); 77% with de novo AML (vs. 67%, p < 0.003)], more favourable cytogenetic prognostic status (23% vs. 6%, p < 0.001), less comorbidities (no comorbidity = 55% vs. 34%, p < 0.001) and treatments proposed were curative 68% (vs. 5.3%, p < 0.001). Factors limiting access to SHU were age over 80 years (OR, 0.14; 95% CI, 0.04-0.38), severe comorbidities (OR, 0.39; 95% CI, 0.21-0.69), emergency unit referral (OR, 0.28; 95% CI, 0.18-0.44) and non-SHU referral (OR, 0.12; 95% CI, 0.07-0.18). Consultation in an academic hospital increased access to SHU by 8.87 times (95% CI, 5.64-14.2). CONCLUSION: The high proportion of access to cytogenetic testing and curative treatment among patients admitted to SHU, and the importance of early treatment in AML underlines the importance of access to SHU for both diagnosis and treatment.
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Hematología , Leucemia Mieloide Aguda , Humanos , Anciano de 80 o más Años , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/terapia , Pronóstico , Análisis Citogenético , Atención al PacienteRESUMEN
BACKGROUND: Refractory anemia with ring sideroblasts associated with marked thrombocytosis was proposed as a provisional entity in the 2001 World Health Organization classification of myeloid neoplasms and also in the 2008 version, but its existence as a single entity is contested. We wish to define the clinical features of this rare myelodysplastic/myeloproliferative neoplasm and to compare its clinical outcome with that of refractory anemia with ring sideroblasts and essential thrombocythemia. DESIGN AND METHODS: We conducted a collaborative retrospective study across Europe. Our database included 200 patients diagnosed with refractory anemia with ring sideroblasts and marked thrombocytosis. For each of these patients, each patient diagnosed with refractory anemia with ring sideroblasts was matched for age and sex. At the same time, a cohort of 454 patients with essential thrombocythemia was used to compare outcomes of the two diseases. RESULTS: In patients with refractory anemia with ring sideroblasts and marked thrombocytosis, depending on the Janus Kinase 2 V617F mutational status (positive or negative) or platelet threshold (over or below 600 × 10(9)/L), no difference in survival was noted. However, these patients had shorter overall survival and leukemia-free survival with a lower risk of thrombotic complications than did patients with essential thrombocythemia (P<0.001) but better survival (P<0.001) and a higher risk of thrombosis (P=0.039) than patients with refractory anemia with ring sideroblasts. CONCLUSIONS: The clinical course of refractory anemia with ring sideroblasts and marked thrombocytosis is better than that of refractory anemia with ring sideroblasts and worse than that of essential thrombocythemia. The higher risk of thrombotic events in this disorder suggests that anti-platelet therapy might be considered in this subset of patients. From a clinical point of view, it appears to be important to consider refractory anemia with ring sideroblasts and marked thrombocytosis as a distinct entity.
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Anemia Refractaria/patología , Anemia Sideroblástica/patología , Janus Quinasa 2/genética , Trombocitemia Esencial/patología , Trombocitosis/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anemia Refractaria/complicaciones , Anemia Refractaria/mortalidad , Anemia Sideroblástica/complicaciones , Anemia Sideroblástica/mortalidad , Plaquetas/patología , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Recuento de Plaquetas , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Trombocitemia Esencial/complicaciones , Trombocitemia Esencial/mortalidad , Trombocitosis/complicaciones , Trombocitosis/mortalidadRESUMEN
BACKGROUND: No robust data assesses the risk of all-cause death and cardiovascular (CV) events in multiple myeloma (MM) patients. PATIENTS AND METHODS: From 1 January to 31 December 2013, 3,381,472 adults were hospitalised (for any reason) in French hospitals. We identified 15,774 patients diagnosed with known MM at baseline. The outcome analysis (all-cause death, CV death, myocardial infarction (MI), ischaemic stroke, or hospitalization for bleedings) was performed with follow-ups starting at the time of the last event. For each MM patient, a propensity score-matched patient without MM was selected. RESULTS: The mean follow-up in the propensity-score-matched population was 3.7 ± 2.3 years. Matched patients with MM had a higher risk of all-death (yearly rate 20.02 vs. 11.39%) than patients without MM. No difference was observed between the MM group and no-MM group for CV death (yearly rate 2.00 vs. 2.02%). The incidence rate of MI and stroke was lower in the MM group: 0.86 vs. 0.97%/y and 0.85 vs. 1.10%/y, respectively. In contrast, MM patients had a higher incidence rate of rehospitalization for major bleeding (3.61 vs. 2.24%/y) and intracranial bleeding (1.03 vs. 0.84%/y). CONCLUSIONS: From a large nationwide database, we demonstrated that MM patients do not have a higher risk of CV death or even a lower risk of both MI and ischaemic stroke. Conversely, MM patients had a higher risk of both major and intracranial bleedings, highlighting the key issue of thromboprophylaxis in these patients.
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Objectives: The UMACOACH Lymphoma is a multidisciplinary monitoring program for patients initiating a first highly haematotoxic treatment for Hodgkin or non-Hodgkin lymphoma. Patient follow-up is based on consultation with a pharmacist and planed phone calls by nurses supervised by a clinical haematologist. Our objective was to assess effectiveness and cost of the UMACOACH Lymphoma Program (ULP) and to investigate patient satisfaction and quality of life (QoL). Methods: This French monocentric case-control study included all patients enrolled in the ULP over a one-year period (cases) matched with retrospective patients receiving usual care (controls). Numbers of adverse events (AEs), re-hospitalisations, average relative dose intensity (ARDI), treatment response and survival were compared between the two groups. Among cases, patient satisfaction and QoL using the EORTC-QLQC30 questionnaire before and after treatment were evaluated. Results: Seventy-eight cases were matched to 78 controls. Twenty-six percent grade 3−4 AEs were observed in cases versus 38% in controls (p = 0.001). There were 76 and 88 re-hospitalisations in the case and control groups, respectively (p = 0.217). ARDI > 85% was observed in 92% and 82% of cases and controls, respectively (p = 0.138). No differences were observed in terms of treatment responses and survival. Estimated cost savings were of EUR 81,782 in favour of the case group. An improvement of 5.1 points was observed in the total QoL score before and after treatment in cases. Conclusions: A nurse−pharmacist−haematologist collaboration seems to be promising to reduce grade 3−4 AEs in HL and NHL patients receiving highly haematotoxic chemotherapy regimens. Cost savings from hospitalisation being avoided were also shown.
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BACKGROUND: Epidemiological data on myeloid malignancies are very rare in the literature due to a lack of registration by cancer registries until 2000. The Registry of Hematologic Malignancies of the Côte d'Or Department in France has, however, steadfastly registered data on cases occurring in the Department since 1980, resulting, to date, in a database of over 5,000 cases classified according to the ICD-O-3 classification, following the most recent World Health Organization classification criteria. DESIGN AND METHODS: Twenty-five years of data on myeloid malignancies, including acute myeloid leukemia, myeloproliferative neoplasms, myelodysplastic syndromes and myelodysplastic/myeloproliferative syndromes were analyzed. World population standardized incidence rates were calculated as were as observed and relative survival. RESULTS: Incidence rates per 100,000 inhabitants/year were 2.5 for acute myeloid leukemia, 1.3 for myelodysplastic syndromes, 3.2 for myeloproliferative neoplasms and 0.6 for myelodysplastic/myeloproliferative syndromes. It was found that the incidence rate of myelodysplastic syndromes increased significantly over the period. The median overall survival is 8.9 months for patients with acute myeloid leukemia, 33.8 months for patients with myelodysplastic syndromes, 91.7 months for those with myeloproliferative neoplasms and 26.6 months for patients with myelodysplastic/myeloproliferative syndromes. Observed and relative 20-year survival rates are, respectively, 12% and 13% in acute myeloid leukemia, 2% and 6% in myelodysplastic syndromes and 20% and 34% in myeloproliferative neoplasms. CONCLUSIONS: These population-based data on myeloid malignancies are the first data collected over such a long period and provide interesting information for clinicians and public health authorities, particularly given the paucity of other long-term, population-based data from cancer registries.
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Leucemia Mieloide Aguda/epidemiología , Síndromes Mielodisplásicos/epidemiología , Trastornos Mieloproliferativos/epidemiología , Adulto , Factores de Edad , Anciano , Femenino , Francia/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Registros , Sistema de Registros , Factores Sexuales , Tasa de Supervivencia , Factores de TiempoRESUMEN
With improvements in acute myeloid leukemia (AML) diagnosis and treatment, more patients are surviving for longer periods. A French population of 9453 AML patients aged ≥15 years diagnosed from 1995 to 2015 was studied to quantify the proportion cured (P), time to cure (TTC) and median survival of patients who are not cured (MedS). Net survival (NS) was estimated using a flexible model adjusted for age and sex in sixteen AML subtypes. When cure assumption was acceptable, the flexible cure model was used to estimate P, TTC and MedS for the uncured patients. The 5-year NS varied from 68% to 9% in men and from 77% to 11% in women in acute promyelocytic leukemia (AML-APL) and in therapy-related AML (t-AML), respectively. Major age-differenced survival was observed for patients with a diagnosis of AML with recurrent cytogenetic abnormalities. A poorer survival in younger patients was found in t-AML and AML with minimal differentiation. An atypical survival profile was found for acute myelomonocytic leukemia and AML without maturation in both sexes and for AML not otherwise specified (only for men) according to age, with a better prognosis for middle-aged compared to younger patients. Sex disparity regarding survival was observed in younger patients with t-AML diagnosed at 25 years of age (+28% at 5 years in men compared to women) and in AML with minimal differentiation (+23% at 5 years in women compared to men). All AML subtypes included an age group for which the assumption of cure was acceptable, although P varied from 90% in younger women with AML-APL to 3% in older men with acute monoblastic and monocytic leukemia. Increased P was associated with shorter TTC. A sizeable proportion of AML patients do not achieve cure, and MedS for these did not exceed 23 months. We identify AML subsets where cure assumption is negative, thus pointing to priority areas for future research efforts.
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Evans' syndrome (ES) is defined as the concomitant or sequential association of warm auto-immune haemolytic anaemia (AIHA) with immune thrombocytopenia (ITP), and less frequently autoimmune neutropenia. ES is a rare situation that represents up to 7% of AIHA and around 2% of ITP. When AIHA and ITP occurred concomitantly, the diagnosis procedure must rule out differential diagnoses such as thrombotic microangiopathies, anaemia due to bleedings complicating ITP, vitamin deficiencies, myelodysplastic syndromes, paroxysmal nocturnal haemoglobinuria, or specific conditions like HELLP when occurring during pregnancy. As for isolated auto-immune cytopenia (AIC), the determination of the primary or secondary nature of ES is important. Indeed, the association of ES with other diseases such as haematological malignancies, systemic lupus erythematosus, infections, or primary immune deficiencies can interfere with its management or alter its prognosis. Due to the rarity of the disease, the treatment of ES is mostly extrapolated from what is recommended for isolated AIC and mostly relies on corticosteroids, rituximab, splenectomy, and supportive therapies. The place for thrombopoietin receptor agonists, erythropoietin, immunosuppressants, haematopoietic cell transplantation, and thromboprophylaxis is also discussed in this review. Despite continuous progress in the management of AIC and a gradual increase in ES survival, the mortality due to ES remains higher than the ones of isolated AIC, supporting the need for an improvement in ES management.
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To observe the effect of the new World Health Organization (WHO) criteria on the incidence of myeloproliferative neoplasms, we performed a retrospective study of a population-based registry in the Côte d'Or area, France, from 1980 to 2007. A total of 524 myeloproliferative neoplasms were registered for the 1980-2007 period, including 135 polycythemia vera, 308 essential thrombocythemia and 81 idiopathic myelofibroses. No change in the incidence of either polycythemia vera or idiopathic myelofibrosis was observed for the 2005-2007 period, compared to 1980-2004. On the contrary, a pronounced increase in the incidence of essential thrombocythemia was noted after 2005, mainly due to the use of JAK2 mutation screening and a lower threshold of platelet count. Our study confirms the relevance of the new WHO diagnostic criteria in allowing earlier diagnosis of essential thrombocythemia.
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Trastornos Mieloproliferativos/diagnóstico , Sistema de Registros/estadística & datos numéricos , Trombocitemia Esencial/diagnóstico , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Francia/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/epidemiología , Estudios Retrospectivos , Trombocitemia Esencial/epidemiología , Organización Mundial de la Salud , Adulto JovenRESUMEN
BACKGROUND: Many different techniques have been designed for the quantification of JAK2V617F allelic burden, sometimes producing discrepant results. DESIGN AND METHODS: JAK2V617F quantification techniques were compared among 16 centers using 11 assays based on quantitative polymerase chain reaction (with mutation-specific primers or probes, or fluorescent resonance energy transfer/melting curve analysis), allele-specific polymerase chain reaction, conventional sequencing or pyrosequencing. RESULTS: A first series of blinded samples (granulocyte DNA, n=29) was analyzed. Seven assays (12 centers) reported values inside the mean +/- 2SD; the mean coefficient of variation was 31%. Sequencing techniques lacked sensitivity, and strong discrepancies were observed with four techniques, which could be attributed to inadequate standards or to different modes of expression of results. Indeed, quantification of JAK2V617F in relation to another control gene produced higher than expected values, suggesting the possibility of more than two JAK2 copies/cell. After calibration of assays with common 1% to 100% JAK2V617F standards (dilutions of UKE-1 cells in normal leukocytes), 14 centers tested ten new samples. JAK2V617F allelic burdens greater or equal than 1% were then reliably quantified by five techniques -- one allele specific-polymerase chain reaction and four TaqMan allele-specific quantitative polymerase chain reaction assays, including one previously giving results outside the mean +/- 2SD -- with a lower mean coefficient of variation (21%). Of these, only the two TaqMan allele-specific quantitative polymerase chain reaction assays with primer-based specificity could detect 0.2% JAK2V617F. CONCLUSIONS: Techniques expressing the allelic burden as JAK2V617F/total JAK2 and using a common set of standards produced similar quantification results but with variable sensitivity. Calibration to a reference standard improved reproducibility.
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Janus Quinasa 2/análisis , Janus Quinasa 2/genética , Reacción en Cadena de la Polimerasa/métodos , Calibración , Línea Celular , ADN/genética , Humanos , Janus Quinasa 2/metabolismo , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/enzimología , Trastornos Mieloproliferativos/genética , Fenilalanina/genética , Fenilalanina/metabolismo , Estándares de Referencia , Reproducibilidad de los Resultados , Valina/genética , Valina/metabolismoRESUMEN
BACKGROUND: In cancer care, the cure proportion (P) and time-to-cure (TTC) are important indicators for practitioners, patients, and healthcare policy makers. The recent definition of TTC as the time at which the probability of belonging to the cured group reaches 95% was used for the first time. METHODS: The data stem from the common database of French cancer registries including 335,358 solid tumours diagnosed between 1995 and 2009 at 27 sites. P and TTC were estimated through a flexible parametric net survival cure model for each cancer site, sex, and age at diagnosis with acceptable assumption of cure (excess mortality rate ≤0.05). RESULTS: TTC was ≤5 years and P was >80% for skin melanoma and thyroid and testis cancers. It was 0 for testis cancer in men <55 and for thyroid cancer in men <45 and women <65. TTC was between 5 and 10 years for all digestive cancers except small intestine and all gynaecologic cancers except breast. It was ≥10 years in prostate, breast, and urinary tract. The range of P according to age and sex was 37-79% for urinary tract 72-88% for prostate and breast, 4-16% for pancreatic and 47-62% for colorectal cancer. CONCLUSION: Time-to-cure was estimated for the first time from a large national database and individual probabilities of cure. It was 0 in the younger patients with testis or thyroid cancer and <12 years in most cancer sites. These results should help improve access to credit and insurance for patients still alive past the estimated TTCs.
Asunto(s)
Neoplasias/epidemiología , Neoplasias/terapia , Adulto , Anciano , Bases de Datos Factuales , Femenino , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Sistema de Registros , Tasa de SupervivenciaRESUMEN
We analyzed the effect of hydroxyurea on the JAK2V617F allelic ratio (%JAK2V617F), measured in purified blood granulocytes, of patients with polycythemia vera and essential thrombocythemia. Thirty-six patients were examined sequentially prior to and after start of hydroxy-urea therapy (8 polycythemia vera, 17 essential thrombocythemia), or while remaining untreated (2 polycythemia vera, 9 essential thrombocythemia). Hydroxyurea therapy (median duration: 15 months) reduced the %JAK2V617F by >30% in 13/25 patients (4 polycythemia vera, 9 essential thrombocythemia). For 3 patients, JAK2V617F remained undetectable for 3-27 months. In addition, a single time point study of two large cohorts of patients, examined either at the time of diagnosis (99 polycythemia vera, 178 essential thrombocythemia) or while receiving hydroxyurea (36 polycythemia vera, 98 essential thrombocythemia; median length of therapy: 32 months), confirmed reduction of %JAK2V617F in the hydroxyurea-treated group (24% vs. 33% JAK2V617F at diagnosis, p<0.01). Prospective studies are needed to determine the prognostic value of reduced JAK2V617F allele burden under cytoreductive therapy.
Asunto(s)
Hidroxiurea/uso terapéutico , Janus Quinasa 2/genética , Policitemia Vera/tratamiento farmacológico , Trombocitemia Esencial/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Sustitución de Aminoácidos , Antidrepanocíticos/uso terapéutico , Estudios de Cohortes , Cartilla de ADN , Femenino , Granulocitos/fisiología , Humanos , Janus Quinasa 2/sangre , Janus Quinasa 2/deficiencia , Masculino , Persona de Mediana Edad , Mutación , Policitemia Vera/genética , Estudios Retrospectivos , Trombocitemia Esencial/genéticaRESUMEN
BACKGROUND: Cure models have been adapted to net survival context to provide important indicators from population-based cancer data, such as the cure fraction and the time-to-cure. However existing methods for computing time-to-cure suffer from some limitations. METHODS: Cure models in net survival framework were briefly overviewed and a new definition of time-to-cure was introduced as the time TTC at which P(t), the estimated covariate-specific probability of being cured at a given time t after diagnosis, reaches 0.95. We applied flexible parametric cure models to data of four cancer sites provided by the French network of cancer registries (FRANCIM). Then estimates of the time-to-cure by TTC and by two existing methods were derived and compared. Cure fractions and probabilities P(t) were also computed. RESULTS: Depending on the age group, TTC ranged from to 8 to 10 years for colorectal and pancreatic cancer and was nearly 12 years for breast cancer. In thyroid cancer patients under 55 years at diagnosis, TTC was strikingly 0: the probability of being cured was >0.95 just after diagnosis. This is an interesting result regarding the health insurance premiums of these patients. The estimated values of time-to-cure from the three approaches were close for colorectal cancer only. CONCLUSIONS: We propose a new approach, based on estimated covariate-specific probability of being cured, to estimate time-to-cure. Compared to two existing methods, the new approach seems to be more intuitive and natural and less sensitive to the survival time distribution.
Asunto(s)
Neoplasias de la Mama/mortalidad , Neoplasias Colorrectales/mortalidad , Neoplasias Pancreáticas/mortalidad , Neoplasias de la Tiroides/mortalidad , Adulto , Anciano , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
INTRODUCTION: Infradiaphragmatic Hodgkin Lymphoma (IDHL) accounts for 3-11% of adult cases of stage I-II Hodgkin Lymphoma and the treatment strategy in IDHL is still heterogeneous. All previous published studies were conducted before the PET-CT era. PET may provide a more accurate evaluation of IDHL stage. The aim of this study was to analyze the clinical and biological characteristics of IDHL patients staged by CT scan or PET-CT in eight French hematology departments and their impact on outcomes in these patients. METHODS: Baseline clinical and biological data and outcomes in patients with a first diagnosis of stage I-II IDHL treated with ABVD +/- radiotherapy were retrospectively collected. RESULTS: Among the 99 patients included, 65 (66%) were staged with PET-CT. These patients were older (53 years vs 46 years, p=0.043), had lower ESR (27 vs 58mm, p=0.022), higher hemoglobin level (13.6 vs 12.8g/dL, p=0.015), less frequent Ann Arbor stage II (74% vs 91%) and less central adenopathy involvement (60% vs 82%, p=0.024). Treatment was chemotherapy alone in 55% of patients and the remaining patients received chemo-radiotherapy (CRT). Five-year PFS and OS rates in PET-CT-staged patients were 78% (95% CI 64-87) and 88% (95% CI 73-95), respectively, compared with 65% (p=0.225) and 82% (p=0.352) in CT-staged patients. The CRT strategy was associated with fewer relapses (p=0.027). CONCLUSION: This study showed that the characteristics of CT-staged IDHL patients were less favorable than those of PET-CT-staged patients and indicated that CRT provided better PFS than did chemotherapy alone.