RESUMEN
OBJECTIVES: The study investigates the hypothesis that inflammation in myelofibrosis (MF) like in myeloma and lymphoma, may disturb iron distribution and contribute to anaemia. METHODS: A cross-sectional study of 80 MF and 23 ET patients was performed. RESULTS: About 35% of anaemic MF patients had functional iron deficiency (FID) with transferrin saturation <20 and normal or elevated S-ferritin (<500 µg/L). In ET, FID was rare. In MF patients with FID, 70.6% were anaemic, vs 29.4% in patients without FID (P = 0.03). Hepcidin was significantly higher in MF patients with anaemia, including transfusion-dependent patients, 50.6 vs 24.4 µg/L (P = 0.01). There was a significant negative correlation between Hb and inflammatory markers in all MF patients: IL-2, IL-6 and TNF-α, (P < 0.01-0.03), LD (P = 0.004) and hepcidin (P = 0.03). These correlations were also seen in the subgroup of anaemic MF patients (Table ). Tsat correlated negatively with CRP (P < 0.001). Symptom burden was heavier in MF patients with FID, and MPN-SAF quality of life scores correlated with IL-6 and CRP. CONCLUSIONS: The inflammatory state of MF disturbs iron turnover, FID is common and contributes to anaemia development and impairment of QoL. Anaemic MF patients should be screened for FID.
Asunto(s)
Anemia Ferropénica/epidemiología , Anemia Ferropénica/etiología , Inflamación/complicaciones , Mielofibrosis Primaria/complicaciones , Mielofibrosis Primaria/epidemiología , Calidad de Vida , Anemia Ferropénica/diagnóstico , Biomarcadores , Análisis Químico de la Sangre , Médula Ósea/patología , Estudios Transversales , Citocinas/sangre , Citocinas/metabolismo , Ferritinas/sangre , Humanos , Inflamación/patología , Mediadores de Inflamación , Hierro/sangre , Mielofibrosis Primaria/patologíaRESUMEN
Evaluation of Anagrelide (Xagrid®) Efficacy and Long-term Safety, a phase IV, prospective, non-interventional study performed in 13 European countries enrolled high-risk essential thrombocythemia patients treated with cytoreductive therapy. The primary objectives were safety and pregnancy outcomes. Of 3721 registered patients, 3649 received cytoreductive therapy. At registration, 3611 were receiving: anagrelide (Xagrid®) (n=804), other cytoreductive therapy (n=2666), or anagrelide + other cytoreductive therapy (n=141). The median age was 56 vs. 70 years for anagrelide vs. other cytoreductive therapy. Event rates (patients with events/100 patient-years) were 1.62 vs. 2.06 for total thrombosis and 0.15 vs. 0.53 for venous thrombosis. Anagrelide was more commonly associated with hemorrhage (0.89 vs. 0.43), especially with anti-aggregatory therapy (1.35 vs. 0.33) and myelofibrosis (1.04 vs. 0.30). Other cytoreductive therapies were more associated with acute leukemia (0.28 vs. 0.07) and other malignancies (1.29 vs. 0.44). Post hoc multivariate analyses identified increased risk for thrombosis with prior thrombohemorrhagic events, age ≥65, cardiovascular risk factors, or hypertension. Risk factors for transformation were prior thrombohemorrhagic events, age ≥65, time since diagnosis, and platelet count increase. Safety analysis reflected published data, and no new safety concerns for anagrelide were found. Live births occurred in 41/54 pregnancies (76%). clinicaltrials.gov Identifier: 00567502.
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Quinazolinas/uso terapéutico , Trombocitemia Esencial/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Transformación Celular Neoplásica , Manejo de la Enfermedad , Progresión de la Enfermedad , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mortalidad , Embarazo , Complicaciones Hematológicas del Embarazo , Estudios Prospectivos , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Medición de Riesgo , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/epidemiología , Resultado del Tratamiento , Adulto JovenRESUMEN
The myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and myelofibrosis, are distinguished by their debilitating symptom profiles, life-threatening complications and profound impact on quality of life. The role gender plays in the symptomatology of myeloproliferative neoplasms remains under-investigated. In this study we evaluated how gender relates to patients' characteristics, disease complications and overall symptom expression. A total of 2,006 patients (polycythemia vera=711, essential thrombocythemia=830, myelofibrosis=460, unknown=5) were prospectively evaluated, with patients completing the Myeloproliferative Neoplasm-Symptom Assessment Form and Brief Fatigue Inventory Patient Reported Outcome tools. Information on the individual patients' characteristics, disease complications and laboratory data was collected. Consistent with known literature, most female patients were more likely to have essential thrombocythemia (48.6% versus 33.0%; P<0.001) and most male patients were more likely to have polycythemia vera (41.8% versus 30.3%; P<0.001). The rate of thrombocytopenia was higher among males than females (13.9% versus 8.2%; P<0.001) and males also had greater red-blood cell transfusion requirements (7.3% versus 4.9%; P=0.02) with shorter mean disease duration (6.4 versus 7.2 years, P=0.03). Despite there being no statistical differences in risk scores, receipt of most therapies or prior complications (hemorrhage, thrombosis), females had more severe and more frequent symptoms for most individual symptoms, along with overall total symptom score (22.8 versus 20.3; P<0.001). Females had particularly high scores for abdominal-related symptoms (abdominal pain/discomfort) and microvascular symptoms (headache, fatigue, insomnia, concentration difficulties, dizziness; all P<0.01). Despite complaining of more severe symptom burden, females had similar quality of life scores to those of males. The results of this study suggest that gender contributes to the heterogeneity of myeloproliferative neoplasms by influencing phenotypic profiles and symptom expression.
Asunto(s)
Trastornos Mieloproliferativos/epidemiología , Fenotipo , Calidad de Vida , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/mortalidad , Pronóstico , Factores Sexuales , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Patients with myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and myelofibrosis, are faced with oppressive symptom profiles that compromise daily functioning and quality of life. Among these symptoms, sexuality-related symptoms have emerged as particularly prominent and largely unaddressed. In the current study, the authors evaluated how sexuality symptoms from MPN relate to other patient characteristics, disease features, treatments, and symptoms. METHODS: A total of 1971 patients with MPN (827 with essential thrombocythemia, 682 with polycythemia vera, 456 with myelofibrosis, and 6 classified as other) were prospectively evaluated and patient responses to the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ C30) were collected, along with information regarding individual disease characteristics and laboratory data. Sexuality scores were compared with an age-matched, healthy control population. RESULTS: Overall, patients with MPN were found to have greater sexual dysfunction compared with the healthy population (MPN-SAF score of 3.6 vs 2.0; P<.001), with 64% of patients with MPN describing some degree of sexual dysfunction and 43% experiencing severe symptoms. The presence of sexual symptoms correlated closely with all domains of patient functionality (physical, social, cognitive, emotional, and role functioning) and were associated with a reduced quality of life. Sexual problems also were found to be associated with other MPN symptoms, particularly depression and nocturnal and microvascular-related symptoms. Sexual dysfunction was more severe in patients aged >65 years and in those with cytopenias and transfusion requirements, and those receiving certain therapies such as immunomodulators or steroids. CONCLUSIONS: The results of the current study identify the topic of sexuality as a prominent issue for the MPN population, and this area would appear to benefit from additional investigation and management. Cancer 2016;122:1888-96. © 2016 American Cancer Society.
Asunto(s)
Trastornos Mieloproliferativos/fisiopatología , Trastornos Mieloproliferativos/psicología , Disfunciones Sexuales Fisiológicas/etiología , Disfunciones Sexuales Psicológicas/etiología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Policitemia Vera/fisiopatología , Policitemia Vera/psicología , Mielofibrosis Primaria/fisiopatología , Mielofibrosis Primaria/psicología , Calidad de Vida , Conducta Sexual , Sexualidad , Encuestas y Cuestionarios , Trombocitemia Esencial/fisiopatología , Trombocitemia Esencial/psicologíaRESUMEN
Symptom burden in myeloproliferative neoplasms (MPNs) is heterogeneous even among patients within the same MPN diagnosis. Using cluster analysis from prospectively gathered symptom burden data in 1470 international patients with essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF), we assessed for the presence of clusters and relationship to disease features and prognosis. In MF (4 clusters identified), clusters significantly differed by Dynamic International Prognostic Scoring System (DIPSS) risk (P < .001), leukopenia (P = .009), thrombocytopenia (P < .001), and spleen size (P = .02). Although an association existed between clusters and DIPSS risk, high symptom burden was noted in some low and intermediate-1-risk MF patients. In PV (5 clusters identified), total symptom score increased across clusters (P < .001), but clusters did not significantly differ by PV risk or the risk assessment variable of age. Among ET patients (5 clusters identified), clusters differed by gender (P = .04), anemia (P = .01), and prior hemorrhage (P = .047). Total symptom score increased across clusters (P < .001), but clusters did not significantly differ by International Prognostic Score for ET risk including the risk assessment variables. Significant symptom heterogeneity exists within each MPN subtype, sometimes independent of disease features or prognosis.
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Neoplasias de la Médula Ósea/epidemiología , Trastornos Mieloproliferativos/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Médula Ósea/complicaciones , Neoplasias de la Médula Ósea/diagnóstico , Análisis por Conglomerados , Femenino , Geografía , Humanos , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/diagnóstico , Policitemia Vera/diagnóstico , Policitemia Vera/epidemiología , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/epidemiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/epidemiologíaRESUMEN
Chemotherapy-induced nausea/vomiting (CINV) is a major problem for patients treated with high-dose chemotherapy (HDCT) conditioning before stem cell transplantation (SCT), both during chemotherapy and afterwards (delayed nausea/vomiting). The standard of care (5-HT3 antagonist and dexamethasone) appears to be ineffective against delayed nausea and vomiting. The objective of this study was to compare standard antiemetic treatment with standard treatment plus prolonged treatment with aprepitant (Emend®) until 7 days after the end of chemotherapy in patients treated with HDCT before autologous SCT. Ninety-six patients were randomized to the experiment (EXP) group receiving Emend in addition to standard antiemetics or to the control (CTR) group receiving placebo. Emend or placebo treatment started 1 h before the first HDCT dose for SCT and ended 7 days after HDCT. Thirty-eight patients in the EXP group experienced complete response (no vomiting) compared to 16 patients in the CTR group. There was a significant difference between the EXP (0.63 ± 2.71) and the CTR (3.72 ± 4.91) group during 10 days after the end of HDCT (p = 0.001) with regard to the number of vomiting episodes. No difference with regard to days of nausea or in the use of antiemetic rescue was noted between the groups. We conclude that standard antiemetic treatment can be improved by addition of aprepitant continued for 7 days after the end of chemotherapy.
Asunto(s)
Antieméticos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Morfolinas/uso terapéutico , Náusea/tratamiento farmacológico , Trasplante de Células Madre , Vómitos/tratamiento farmacológico , Adulto , Anciano , Aprepitant , Dexametasona/uso terapéutico , Esquema de Medicación , Quimioterapia Combinada , Femenino , Humanos , Linfoma/terapia , Masculino , Persona de Mediana Edad , Morfolinas/administración & dosificación , Mieloma Múltiple/terapia , Náusea/inducido químicamente , Náusea/prevención & control , Antagonistas del Receptor de Serotonina 5-HT3/uso terapéutico , Resultado del Tratamiento , Vómitos/inducido químicamente , Vómitos/prevención & controlRESUMEN
Available information is limited regarding the use of cytoreductive combination therapy in high-risk patients with essential thrombocythemia. This analysis aims to evaluate the clinical relevance and patterns of cytoreductive combination treatment in European high-risk patients with essential thrombocythemia in the Evaluation of Xagrid(®) Efficacy and Long-term Safety study. Of 3643 patients, 347 (9.5%) received combination therapy. Data were recorded at each 6-month update. Of 347 patients who received combination therapy, 304 (87.6%) received hydroxycarbamide + anagrelide. Monotherapies received before this combination were hydroxycarbamide (n=167, 54.9%) and anagrelide (n=123, 40.5%). Median weekly doses of hydroxycarbamide and anagrelide were: 7000 and 10.5 mg when used as prior monotherapy; 3500 and 7.0 mg when used as add-on treatment. Overall, median platelet counts were 581 × 10(9)/L and 411 × 10(9)/L before and after starting hydroxycarbamide + anagrelide, respectively. In patients with paired data (n=153), the number of patients with platelet counts less than 400 × 10(9)/L increased from 33 (21.6%) to 74 (48.4%; P<0.0001), and with platelet counts less than 600 × 10(9)/L, from 82 (53.6%) to 132 (86.3%; P<0.0001). Hydroxycarbamide + anagrelide was discontinued in 158 patients: 76 (48.1%) stopped hydroxycarbamide, 59 (37.3%) stopped anagrelide, 19 (12.0%) stopped both and 4 (2.5%) had another therapy added. The most frequent reasons for discontinuation were intolerance/side-effects, lack of efficacy, and therapeutic strategy. Combination therapy, usually hydroxycarbamide + anagrelide, is used in approximately 10% of all high-risk patients with essential thrombocythemia and may be a useful approach in treating patients for whom monotherapy is unsatisfactory. (Clinicaltrials.gov identifier:NCT00567502).
Asunto(s)
Hidroxiurea/uso terapéutico , Quinazolinas/uso terapéutico , Trombocitemia Esencial/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Recuento de Células Sanguíneas , Quimioterapia Combinada , Femenino , Humanos , Hidroxiurea/administración & dosificación , Hidroxiurea/efectos adversos , Interferones/administración & dosificación , Interferones/efectos adversos , Interferones/uso terapéutico , Masculino , Persona de Mediana Edad , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Trombocitemia Esencial/diagnóstico , Resultado del Tratamiento , Adulto JovenRESUMEN
Symptomatic burden in myeloproliferative neoplasms is present in most patients and compromises quality of life. We sought to validate a broadly applicable 18-item instrument (Myeloproliferative Neoplasm Symptom Assessment Form [MPN-SAF], coadministered with the Brief Fatigue Inventory) to assess symptoms of myelofibrosis, essential thrombocythemia, and polycythemia vera among prospective cohorts in the United States, Sweden, and Italy. A total of 402 MPN-SAF surveys were administered (English [25%], Italian [46%], and Swedish [28%]) in 161 patients with essential thrombocythemia, 145 patients with polycythemia vera, and 96 patients with myelofibrosis. Responses among the 3 administered languages showed great consistency after controlling for MPN subtype. Strong correlations existed between individual items and key symptomatic elements represented on both the MPN-SAF and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30. Enrolling physicians' blinded opinion of patient symptoms (6 symptoms assessed) were highly correlated with corresponding patients' responses. Serial administration of the English MPN-SAF among 53 patients showed that most MPN-SAF items are well correlated (r > 0.5, P < .001) and highly reproducible (intraclass correlation coefficient > 0.7). The MPN-SAF is a comprehensive and reliable instrument that is available in multiple languages to evaluate symptoms associated with all types of MPNs in clinical trials globally.
Asunto(s)
Neoplasias de la Médula Ósea/diagnóstico , Trastornos Mieloproliferativos/diagnóstico , Encuestas y Cuestionarios , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Médula Ósea/epidemiología , Estudios de Cohortes , Femenino , Encuestas Epidemiológicas , Humanos , Internacionalidad , Italia/epidemiología , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/epidemiología , Calidad de Vida , Registros , Reproducibilidad de los Resultados , Suecia/epidemiología , Estados Unidos/epidemiologíaRESUMEN
A rapid and easy-to-use test kit, EPO WGA MAIIA, which can be used for distinguishing various endogenous human erythropoietins (hEPOs) and several recombinant hEPO and EPO analogues, has been evaluated. The test is based on chromatographic separation of the glycosylated isoforms of EPO using wheat germ agglutinin (WGA) and a sensitive immunoassay using anti-EPO carbon black nanostrings and image scanning for quantification. All of the reactions take place along the porous layer of a lateral flow microcolumn containing WGA and anti-EPO zones. The presence of molecules resembling hEPOs, such as Mircera, was detected by the aberrant affinity interaction with the antibody zone on the strip. It was possible to distinguish nine recombinant hEPOs expressed in hamster and human cell lines, as well as Aranesp and Mircera, from endogenous urine hEPO. The required amount of EPO in the samples, a few picograms, is very low compared with other methods for EPO isoform identification. This EPO isoform determination method opens the possibility to monitor recombinant EPO therapy for clinical research and seems to be a valuable candidate to the arsenal of EPO doping control tests.
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Análisis Químico de la Sangre/métodos , Hematínicos/sangre , Hematínicos/orina , Urinálisis/métodos , Adulto , Anticuerpos/inmunología , Análisis Químico de la Sangre/instrumentación , Eritropoyesis/efectos de los fármacos , Eritropoyetina/sangre , Eritropoyetina/inmunología , Eritropoyetina/metabolismo , Eritropoyetina/orina , Femenino , Hematínicos/farmacología , Humanos , Inmunoensayo , Masculino , Persona de Mediana Edad , Polietilenglicoles , Isoformas de Proteínas/sangre , Isoformas de Proteínas/inmunología , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/orina , Factores de Tiempo , Urinálisis/instrumentación , Aglutininas del Germen de Trigo/metabolismo , Adulto JovenRESUMEN
European experts were convened to develop a definition of response to treatment in polycythemia vera (PV) and essential thrombocythemia (ET). Clinicohematologic (CH), molecular, and histologic response categories were selected. In ET, CH complete response (CR) was: platelet count less than or equal to 400 x 10(9)/L, no disease-related symptoms, normal spleen size, and white blood cell count less than or equal to 10 x 10(9)/L. Platelet count less than or equal to 600 x 10(9)/L or a decrease greater than 50% was partial response (PR). In PV, CH-CR was: hematocrit less than 45% without phlebotomy, platelet count less than or equal to 400 x 10(9)/L, white blood cell count less than or equal to 10 x 10(9)/L, and no disease-related symptoms. A hematocrit less than 45% without phlebotomy or response in 3 or more of the other criteria was defined as PR. In both ET and in PV, molecular CR was a reduction of any molecular abnormality to undetectable levels. Molecular PR was defined as a reduction more than or equal to 50% in patients with less than 50% mutant allele burden, or a reduction more than or equal to 25% in patients with more than 50% mutant allele burden. Bone marrow histologic response in ET was judged on megakaryocyte hyperplasia while on cellularity and reticulin fibrosis in PV. The combined use of these response definitions should help standardize the design and reporting of clinical studies.
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Policitemia Vera/diagnóstico , Policitemia Vera/terapia , Guías de Práctica Clínica como Asunto , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/terapia , Consenso , Europa (Continente) , Humanos , Pronóstico , Inducción de Remisión , Sociedades Médicas/organización & administraciónRESUMEN
OBJECTIVE: Anaemia in low-risk myelodysplastic syndromes (MDS) is associated with reduced quality of life (QoL). Response to treatment with erythropoietin ± granulocyte colony-stimulating factor (G-CSF) is associated with improved QoL, but whether transfusion therapy with higher haemoglobin (Hb) target levels has similar effects is unknown. The objective for this prospective phase II Nordic multicentre trial was to assess QoL, response rate and physical function in elderly anaemic MDS patients treated to a target Hb level of >120 g/L. METHODS: Thirty-six elderly patients with low- and intermediate-1 risk MDS received darbepoetin (DA) 300 µg/wk, with the addition of G-CSF if no response. If the Hb target was reached at 16 wk, treatment was maintained until week 26. Remaining patients were transfused to reach the target level for at least 8 wk. RESULTS: Twenty-seven patients completed the study. Response rate to DA ± G-CSF was 67% in evaluable patients and 56% according to intention to treat. Eighteen patients reached the target Hb level according to protocol. QoL scores for fatigue, dyspnoea, constipation, and physical, role and social functioning improved significantly during study, with similar results for transfused and untransfused patients. Maintaining Hb >120 g/L did not confer a higher transfusion rate, once the target was reached. In two of fourteen patients, magnetic resonance imaging T2* indicated cardiac iron overload, however, without association with ferritin levels. CONCLUSIONS: In elderly anaemic MDS patients, an increment in haemoglobin is associated with improved QoL, whether induced by growth factor treatment or transfusion therapy.
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Hemoglobinas/análisis , Imagen por Resonancia Magnética/métodos , Síndromes Mielodisplásicos/terapia , Calidad de Vida , Anciano , Anciano de 80 o más Años , Darbepoetina alfa , Transfusión de Eritrocitos , Eritropoyetina/administración & dosificación , Eritropoyetina/análogos & derivados , Femenino , Ferritinas/sangre , Filgrastim , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Masculino , Síndromes Mielodisplásicos/tratamiento farmacológico , Proteínas Recombinantes , Resultado del TratamientoRESUMEN
Recommendations regarding management of essential thrombocythaemia rely on studies done before the discovery of the CALR mutation. On May 20, 2020, the European LeukemiaNet annual meeting was held with the goal to identify unmet clinical needs in myeloproliferative neoplasms. Because patients with a CALR mutation have specific clinical characteristics, treatment of CALR-mutated essential thrombocythaemia was considered an unmet clinical need by the European LeukemiaNet. The elaboration of a consensus document with recommendations according to current evidence was proposed as a solution for resolving uncertainties in the treatment of CALR-mutated essential thrombocythaemia. A steering committee comprising four European LeukemiaNet members was then formed and a panel of ten experts in the field was recruited. The experts proposed 51 potential unmet clinical needs in the management of CALR-mutated essential thrombocythaemia and were asked to score the relevance of each topic. Those topics that obtained the highest scores as relevant unmet clinical needs were identified, including antiplatelet therapy in patients at low risk, definition of extreme thrombocytosis and its management in patients at low risk, indications of cytoreduction and targets of therapy, first-line treatment of choice in young patients (<60 years), and management of pregnancy. After the steering committee revised the available evidence for each topic, a consensus on management and proposal for improving knowledge was achieved by use of an email-based, two round, Delphi approach. Consensus was achieved when 90% of the panellists agreed with a statement and included 14 recommendations and six solution proposals. Key recommendations included careful observation for asymptomatic patients with classical, low-risk, CALR-mutated essential thrombocythaemia without cardiovascular risk factors; caution in the use of antiplatelet therapy for symptomatic patients at low risk with platelet counts of 1000-1500 × 109 platelets per L, in such cases cytoreduction is an adequate option, especially if adquired Von Willebrand disease is present; cytoreduction is recommended for extreme thrombocytosis (platelet count >1500 × 109 platelets per L) with pegylated interferon alfa being the preferred option for younger patients; both hydroxycarbamide and anagrelide might be given to patients ineligible for pegylated interferon alfa; and treatment algorithms for patients with high-risk pregnancies should not be changed according to genotype. The European LeukemiaNet proposes to use these recommendations in the routine management of patients with CALR-mutated essential thrombocythaemia, and designing new clinical studies in this field might be useful.
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Inhibidores de Agregación Plaquetaria/uso terapéutico , Trombocitemia Esencial/tratamiento farmacológico , Factores de Edad , Calreticulina/genética , Femenino , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Recuento de Plaquetas , Embarazo , Índice de Severidad de la Enfermedad , Trombocitemia Esencial/genética , Trombocitemia Esencial/patologíaRESUMEN
Anemia is a widely prevalent complication among cancer patients. At the time of diagnosis, 30% to 40% of patients with non-Hodgkin lymphoma or Hodgkin lymphoma and up to 70% of patients with multiple myeloma are anemic; rates are higher among persons with myelodysplastic syndromes. Among patients with solid cancers or lymphomas, up to half develop anemia following chemotherapy. For almost 2 decades, erythropoiesis-stimulating agents (ESAs) were the primary treatment for cancer-related anemia. However, reassessments of benefits and risks of ESAs for cancer-associated anemia have occurred internationally. We reviewed guidelines and notifications from regulatory agencies and manufacturers, reimbursement policies, and utilization for ESAs in the cancer and chronic kidney disease settings within the United States, Europe, and Canada. In 2008 the US Food and Drug Administration (FDA) restricted ESAs from cancer patients seeking cure. Reimbursement is limited to hemoglobin levels < 10 g/dL. In the United States, ESA usage increased 340% between 2001 and 2006, and decreased 60% since 2007. The European Medicines Agency (EMEA) recommended that ESA benefits do not outweigh risks. In Europe between 2001 and 2006, ESA use increased 51%; since 2006, use decreased by 10%. In 2009, Canadian manufacturers recommended usage based on patient preferences. In Canada in 2007, approximately 20% of anemic cancer patients received ESAs, a 20% increase since 2004. In contrast to Europe, where ESA use has increased over time, reassessments of ESA-associated safety concerns in the United States have resulted in marked decrements in ESA use among cancer patients.
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Anemia/tratamiento farmacológico , Antineoplásicos/efectos adversos , Guías como Asunto , Hematínicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Anemia/inducido químicamente , Revisión de la Utilización de Medicamentos , Europa (Continente) , Humanos , Estados UnidosRESUMEN
AIM AND OBJECTIVE: To investigate if oral cryotherapy during myeloablative therapy may influence frequency and severity of mucositis, nutritional status and infection rate after bone marrow transplantation. BACKGROUND: Patients treated with intensive myeloablative treatment before bone marrow transplantation are all at risk to develop mucositis. Oral mucositis causes severe pain and oral dysfunction, which can contribute to local and systemic infections and bleeding; it may even interrupt cancer therapy. Oral mucositis also decreases the oral food intake, which increases the risk for malnutrition and infection. Reduced food intake, loss of fat and muscles, alterations in energy and substrate metabolism leads to malnutrition. DESIGN: A randomised controlled trial with a random assignment to experimental or control group. METHOD: A stratified randomisation was used with regard to the type of transplantation. Mucositis was measured on WHO mucositis scale. Number of days of total parenteral nutrition, infection rate, weight, albumin levels and days at hospital was compared. RESULTS: There were significantly fewer patients in the experimental group with mucositis grade 3-4 than in the control group and significantly lower number of days in the hospital (allogeneic patients). Less total parenteral nutrition was needed in the experimental group in both settings, and the S-albumin level was significantly better preserved. No significant difference could be found with regard to infection rate. CONCLUSION: Oral cryotherapy reduced mucositis, number of hospital days, the need for total parenteral nutrition and resulted in a better nutritional status. RELEVANCE TO CLINICAL PRACTICE: Nurses caring for patients treated with myeloablative therapy should place high priority to prevent oral mucositis and hereby reduce its side effects.
Asunto(s)
Crioterapia , Estado Nutricional , Estomatitis/terapia , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: In order to facilitate sound economic evaluations of novel treatments, health-economic models of polycythemia vera (PV) must combine effects on surrogate endpoints in trials with disease progression (DP) and mortality in long-term cohort data. OBJECTIVE: We validate an economic model for PV that uses Janus Kinase 2 (JAK2) burden as a surrogate endpoint to predict DP (thrombosis, myelofibrosis, and acute leukemia) and overall survival (OS) based on progression-specific mortality. METHODS: Long-term observational studies that include information about baseline JAK2 burden were identified via PubMed searches and used to validate the model. Kaplan-Meier (KM) OS curves were extracted using a digitizing software. External validity of the model was analyzed by visually comparing OS curves of the model with the KM curves of the included studies, as well as calculating differences in mean OS estimated as area under the curve (AUC). RESULTS: The model's predictions of cumulative DP were somewhat lower than the published studies. Over 20 years' time, our base case model predicted a mean OS for a PV patient (15.0-16.5 years), which was in line with the published studies (15.8-17.5 years). Modeled mean OS was almost two years longer (1.6-1.9 years) for patients with JAK2 <50% than patients with JAK2 ≥50%. Only three long-term observational studies that satisfied the predefined criteria were found and could be used in the validation, but these studies did not capture JAK2 evolution over time. Improved model predictions of DP and mortality based on the longitudinal evolution of JAK2 could be derived from real-world data sources. Such data are currently scarce and future observational studies should be designed to capture the long-term impact of JAK2 on DP and mortality in PV. CONCLUSIONS: Our model, based on JAK2 burden as a marker for DP, generated OS estimations that are in line with results of published data.
RESUMEN
Risk stratification is the basis for treatment decisions in the chronic myeloproliferative disorders, and in addition to the three established risk factors of previous thrombosis, age and platelets >1500 x 10(9), cardiovascular risk factors should be addressed. In addition, premorbidity with regard to possible side effects of platelet-reducing drugs as well as the impact on quality of life of such side effects should be considered. The near-to-normal life expectancy and long term nature of treatment also makes it necessary to consider the potential leukaemogenic effects of some cytostatic drugs.
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Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/tratamiento farmacológico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Manejo de la Enfermedad , Humanos , Calidad de Vida , Medición de Riesgo , Factores de RiesgoRESUMEN
Essential thrombocythaemia (ET) is an acquired myeloproliferative disorder with a prolonged clinical course and a near-normal life expectancy. Therapy is stratified according to risk of thrombohaemorrhagic events. In high-risk patients, platelet reduction is generally recommended. In intermediate-risk patients, therapy should be considered depending on the severity of associated risk factors, especially cardiovascular. In low-risk patients, a watch-and-wait approach is appropriate. Hydroxycarbamide is generally first-line therapy. Concerns for possible leukemogenicity make anagrelide or interferon-alpha possible choices in younger patients and those who are resistant or intolerant to hydroxycarbamide. Each pharmacotherapy is associated with specific long-term risks and benefits. The potential risk of major bleeding is the main drawback of aspirin. Hydroxycarbamide is an established, effective drug for ET, but it may increase the risk of transformation to acute myeloid leukaemia and may give mucocutaneous ulcers. Anagrelide is a licensed treatment that also reduces platelet counts and is generally well tolerated, with evidence that some common side effects diminish over time. Anagrelide can have cardiac effects due to inhibition of phosphodiesterase III and therefore requires cautious use in patients with cardiac insufficiency. There is no evidence of leukaemogenicity with anagrelide or interferon-alpha therapy. Interferon-alpha is the only treatment suitable for use during pregnancy, although it is not licensed in ET. While it is effective for platelet reduction, the use of interferon-alpha is restricted by psychiatric side effects. Our knowledge of the optimum pharmacotherapy for each patient with ET continues to evolve through research and clinical trials, particularly into the molecular basis of the disease.
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Trombocitemia Esencial/fisiopatología , Trombocitemia Esencial/terapia , Trombocitosis/fisiopatología , Trombocitosis/terapia , Algoritmos , Antineoplásicos/uso terapéutico , Aspirina/uso terapéutico , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Hidroxiurea/uso terapéutico , Interferón-alfa/uso terapéutico , Janus Quinasa 2/genética , Embarazo , PubMed , Quinazolinas , Ensayos Clínicos Controlados Aleatorios como Asunto , Trombocitemia Esencial/diagnóstico , Trombocitosis/diagnósticoRESUMEN
BACKGROUND: An alumni study of graduates from the medical school in Uppsala, was performed to give input into an ongoing reform process. AIMS: This study aimed to investigate how medical interns view their undergraduate medical education and the extent to which they felt that the curriculum prepared them for their current positions. METHODS: A web-based questionnaire was sent out via mail in 2005 to all past graduates who had qualified in Uppsala in 2003. RESULTS: Replies were obtained from 69 of 102 students (68%). The most apparent suggested change of the education was increased integration of preclinical and clinical teaching. Correlations were found between student satisfaction with the medical school and perceived teacher attitude, encouragement to reflect, and the graduates' perception of having sufficient practical abilities. Significant gender differences were found regarding perceived clinical ability and concerning feedback and encouragement from the teachers. CONCLUSIONS: Our results suggest more direct feedback from the teachers and more integration between basic sciences and clinical education. Female and male students may have different needs. A key question is therefore to encourage teachers to learn about gender since female and male students should equally experience respectful encounters with teachers and doctors acting as role models.
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Comportamiento del Consumidor , Educación de Pregrado en Medicina/normas , Internado y Residencia , Médicos/psicología , Femenino , Humanos , Masculino , Factores Sexuales , Encuestas y Cuestionarios , SueciaRESUMEN
Anagrelide is often used in the treatment of thrombocythemia in myeloproliferative disease (MPD), but information concerning effects of treatment on cytokines involved in regulation of blood platelet levels is limited. Here, we investigated serum levels of thrombopoietin (TPO) and soluble IL-6 receptor (sIL-6R) in relation to response to treatment with and plasma concentrations of anagrelide. Samples from 45 patients with thrombocythemia due to MPD (ET=31, PV=14), being treated with anagrelide for 6 months, were analyzed for TPO, sIL-6R and anagrelide levels. The mean baseline platelet count was 983x10(9)/L. A reduction of platelets to <600 in asymptomatic or <400 x 10(9)/L in symptomatic patients was defined as a complete remission (CR), a reduction with >50% of baseline as partial remission, and <50% reduction as failure. At 6 months, 35 patients were in CR, 1 had a partial remission and 9 were treatment failures. For all patients, there was an increase in TPO of 44% from baseline; this change was more pronounced for patients with partial remission and failure. sIL-6R levels did not change significantly. There was no correlation between levels of anagrelide and cytokine levels at 6 months, and changes of cytokine levels did not relate to changes of platelet counts. Thus, a pronounced increase of TPO levels after 6 months of anagrelide treatment indicated that this treatment affected a major regulatory mechanism for megakaryocyte and platelet formation in MPD.
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Inhibidores de Agregación Plaquetaria/uso terapéutico , Quinazolinas/uso terapéutico , Receptores de Interleucina-6/sangre , Trombocitosis/tratamiento farmacológico , Trombopoyetina/sangre , Adulto , Anciano , Humanos , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/sangre , Recuento de Plaquetas , Quinazolinas/sangre , Resultado del TratamientoRESUMEN
BACKGROUND: The relationship between medical students' well-being, motivation, and their conceptions of learning and knowledge has not been previously explored. AIMS: This study aimed to validate a research instrument intending to measure medical students' (n = 280) (1) experiences of stress, anxiety and disinterest, (2) motivational (thinking) strategies, (3) conceptions of learning and knowledge (epistemologies), and (4) approaches to learning. METHODS: We developed an instrument, MED NORD, which is a composition of scales measuring different theoretical constructs that previously have shown good predictive value, validity and reliability. A principal component analysis with Varimax-rotation was performed in order to see how the scales related to each other. RESULTS: The internal consistency reliability was found to be satisfactory or good for each scale. The results showed five factors: Dysfunctional Orientation, Collaborative Knowledge Building Orientation, Cookbook Orientation, Social Orientation, and Individual Abilities Orientation. These study orientations were related to how medical students perceived their learning environment. CONCLUSIONS: The new tool showed consistency and validity and was judged appropriate for future use in measuring medical students' well-being and study orientations.