RESUMEN
The incidence of venous thromboembolism (VTE) for non-hospitalised patients with coronavirus disease-2019 infection has not been very widely studied. 13 019 persons with a positive SARS-CoV-2 nucleic acid amplification test were identified. In total, 447 (0.2%) VTEs were identified in the study population, 293 (66%) of these were pulmonary embolisms. A positive SARS-CoV-2 test did not increase the risk for VTE in the univariate analysis (odds ratio (OR): 1.0, 95% confidence interval (CI): 0.69-1.4) or multivariable analysis (OR: 1.36, 95% CI: 0.93-1.97).
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COVID-19 , Embolia Pulmonar , Tromboembolia Venosa , Trombosis de la Vena , Humanos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , COVID-19/complicaciones , SARS-CoV-2 , Factores de Riesgo , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/epidemiología , Embolia Pulmonar/etiologíaRESUMEN
PURPOSE: High sodium intake is an accepted risk factor for hypertension, while low Na+ intake has also been associated with increased risk of cardiovascular events. In this cross-sectional study, we examined the association of 24-h urinary Na+ excretion with haemodynamics and volume status. MATERIALS AND METHODS: Haemodynamics were recorded in 510 normotensive and never-treated hypertensive subjects using whole-body impedance cardiography and tonometric radial artery pulse wave analysis. The results were examined in sex-specific tertiles of 24-h Na+ excretion, and comparisons between normotensive and hypertensive participants were also performed. Regression analysis was used to investigate factors associated with volume status. The findings were additionally compared to 28 patients with primary aldosteronism. RESULTS: The mean values of 24-h urinary Na+ excretion in tertiles of the 510 participants were 94, 148 and 218 mmol, respectively. Average tertile age (43.4-44.7 years), office blood pressure and pulse wave velocity were corresponding in the tertiles. Plasma electrolytes, lipids, vitamin D metabolites, parathyroid hormone, renin activity, aldosterone, creatinine and insulin sensitivity did not differ in the tertiles. In supine laboratory recordings, there were no differences in aortic systolic and diastolic blood pressure, heart rate, cardiac output and systemic vascular resistance. Extracellular water volume was higher in the highest versus lowest tertile of Na+ excretion. In regression analysis, body surface area and 24-h Na+ excretion were independent explanatory variables for extracellular water volume. No differences in urine Na+ excretion and extracellular water volume were found between normotensive and hypertensive participants. When compared with the 510 participants, patients with primary aldosteronism had 6.0% excess in extracellular water (p = .003), and 24-h Na+ excretion was not related with extracellular water volume. CONCLUSION: In the absence of mineralocorticoid excess, Na+ intake, as evaluated from 24-h Na+ excretion, predominantly influences extracellular water volume without a clear effect on blood pressure.
We evaluated sodium intake in 510 subjects by measuring their 24-h sodium excretion to the urine and examined whether sodium intake was related with alterations in cardiovascular function and fluid balance. All participants were without blood pressure lowering medications.Blood pressure was recorded by a device that senses the radial artery pulsations form the wrist. The amount of blood pumped by the heart, the transfer of pressure waves following cardiac contractions and body fluid status were evaluated using bioimpedance, a method recording changes in body electrical resistance.For the analyses, the participants were divided into tertiles according to their 24-h sodium excretions. We also compared results between normotensive and hypertensive subjects.The 24-h sodium excretion in the tertiles corresponded to about 6 g, 9 g and 13 g of salt intake per day, respectively. There were no differences between the tertiles in age, routine laboratory analyses, blood pressure, large arterial stiffness, amount blood pumped by the heart and resistance to blood flow in the arteries. However, there was more extracellular fluid in the highest versus the lowest tertile of sodium excretion. Further statistics indicated that extracellular fluid volume in the body was mainly determined by body size, but it was also moderately influenced by sodium intake.No differences in 24-h sodium excretion and extracellular water volume were found between normotensive and hypertensive participants.In subjects not using blood pressure lowering medications, sodium intake predominantly influences the amount of extracellular fluid without a clear effect on blood pressure.
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Hiperaldosteronismo , Hipertensión , Masculino , Femenino , Humanos , Adulto , Presión Sanguínea/fisiología , Agua , Estudios Transversales , Análisis de la Onda del Pulso , Sodio/orinaRESUMEN
OBJECTIVES: AML-2003 study sought to compare the long-term efficacy and safety of IAT and IdAraC-Ida in induction chemotherapy of acute myeloid leukemia (AML) and introduce the results of an integrated genetic and clinical risk classification guided treatment strategy. METHODS: Patients were randomized to receive either IAT or IdAraC-Ida as the first induction treatment. Intensified postremission strategies were employed based on measurable residual disease (MRD) and risk classification. Structured questionnaire forms were used to gather data prospectively. RESULTS: A total of 356 AML patients with a median age of 53 years participated in the study. Long-term overall survival (OS) and relapse-free survival (RFS) were both 49% at 10 years. The median follow-up was 114 months. No significant difference in remission rate, OS or RFS was observed between the two induction treatments. Risk classification according to the protocol, MRD after the first and the last consolidation treatment affected the OS and RFS significantly (p < .001). CONCLUSIONS: Intensified cytarabine dose in the first induction treatment was not better than IAT in patients with AML. Intensification of postremission treatment in patients with clinical risk factors or MRD seems reasonable, but randomized controlled studies are warranted in the future.
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Idarrubicina , Leucemia Mieloide Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Citarabina/uso terapéutico , Finlandia , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Persona de Mediana Edad , Neoplasia Residual , Estudios Prospectivos , Inducción de Remisión , Tioguanina/uso terapéuticoRESUMEN
OBJECTIVES: The aim was to identify the clinical characteristics, outcome, and antimicrobial susceptibility of healthcare-associated bloodstream infections (BSIs) in hematological patients. METHODS: This retrospectively collected laboratory-based surveillance data include 3404 healthcare-associated BSIs in 2296 patients with a hematological malignancy in hospitals participating in the Finnish Hospital Infection Program from January 1, 2006, to December 31, 2016. RESULTS: The most common underlying diseases were acute myelogenous leukemia (35%) and non-Hodgkin lymphoma (22%). Gram-positive organisms accounted for 60%-46% and gram-negative organisms for 24%-36% of BSIs in 2006-2016. The most common causative organism was coagulase-negative staphylococci (CoNS) (n = 731). The 7- and 28-day case fatality rates were 5.2% and 11.4%, respectively, and was highest in BSIs caused by Candida species (10.8% and 30.8%). The median age of patients increased from 59 years in 2006-2008 to 62 years in 2015-2016 (P < .01). Five percent of S aureus isolates were resistant to methicillin and five percent of Pseudomonas aeruginosa isolates were multidrug-resistant. Four percent of Klebsiella and seven percent of E coli isolates were resistant to ceftazidime. CONCLUSIONS: The proportion of gram-positive bacteria decreased and gram-negative bacteria increased over time. The case fatality rate was low and the median age of patients increased during the study.
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Candidiasis/epidemiología , Infección Hospitalaria/epidemiología , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Grampositivas/epidemiología , Leucemia Mieloide Aguda/epidemiología , Linfoma no Hodgkin/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Antifúngicos/uso terapéutico , Candidiasis/complicaciones , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Niño , Preescolar , Infección Hospitalaria/complicaciones , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología , Farmacorresistencia Bacteriana , Farmacorresistencia Fúngica , Femenino , Finlandia/epidemiología , Infecciones por Bacterias Gramnegativas/complicaciones , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Grampositivas/complicaciones , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Incidencia , Lactante , Recién Nacido , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/microbiología , Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/microbiología , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Heparin-induced thrombocytopenia (HIT) usually appears at 5 to 10 days after initiation of heparin. Autoimmune HIT can arise after discontinuation of heparin treatment (delayed-onset HIT) or without any preceding heparin exposure (spontaneous HIT syndrome). CASE REPORT: This case presents a course of autoimmune HIT with delayed onset. The patient was hospitalized due to influenza pneumonia and received low-molecular-weight heparin thromboprophylaxis for 9 days. Seven days after discharge, she was readmitted because of a cerebral sinus vein thrombosis and severe thrombocytopenia. Intracranial bleeding and brain infarction caused her death. DISCUSSION: Autoimmune HIT was confirmed by functional heparin-induced platelet (PLT) activation test. Intracranial bleeding prevented continuous and effective anticoagulation. PLT transfusions were given, although they are generally advised against in HIT patients due to potential risk of thromboembolic events. CONCLUSION: This case presents that testing PLT-activating antibodies both in the presence and in the absence of current heparin treatment helps to diagnose patients with autoimmune HIT. There is conflicting evidence to refuse PLT transfusion when HIT is complicated with life-threatening bleeding.
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Autoanticuerpos/sangre , Heparina de Bajo-Peso-Molecular , Trombosis Intracraneal , Activación Plaquetaria , Púrpura Trombocitopénica Idiopática , Femenino , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/efectos adversos , Heparina de Bajo-Peso-Molecular/química , Humanos , Gripe Humana/sangre , Gripe Humana/tratamiento farmacológico , Trombosis Intracraneal/sangre , Trombosis Intracraneal/inducido químicamente , Persona de Mediana Edad , Neumonía Viral/sangre , Neumonía Viral/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/sangre , Púrpura Trombocitopénica Idiopática/inducido químicamente , Factores de TiempoRESUMEN
POEMS syndrome is a rare para-neoplastic syndrome secondary to a plasma cell dyscrasia. Effective treatment can control the disease-related symptom complex. We describe the clinical outcome of autologous stem cell transplantation for patients with POEMS syndrome, determining the impact of patient- and disease-specific factors on prognosis. One hundred and twenty-seven patients underwent an autologous stem cell transplantation between 1997-2010 with a median age of 50 years (range 26-69 years). Median time from diagnosis to autologous stem cell transplantation was 7.5 months with 32% of patients receiving an autologous stem cell transplantation more than 12 months from diagnosis. Engraftment was seen in 97% patients and engraftment syndrome was documented in 23% of autologous stem cell transplantation recipients. Hematologic response was characterized as complete response in 48.5%, partial response in 20.8%, less than partial repsonse in 30.7%. With a median follow up of 48 months (95%CI: 38.3, 58.6), 90% of patients are alive and 16.5% of patients have progressed. The 1-year non-relapse mortality was 3.3%. The 3-year probabilities of progression-free survival and overall survival are 84% and 94%, respectively, with 5-year probabilities of progression-free survival and overall survival of 74% and 89%. In a cohort of graft recipients, detailed organ-specific symptom response demonstrated clear symptom benefit after autologous stem cell transplantation especially in relation to neurological symptom control. The data analyzed in this study demonstrate the clinical utility of autologous stem cell transplantation for patients with POEMS syndrome.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Síndrome POEMS/terapia , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Síndrome POEMS/diagnóstico , Síndrome POEMS/mortalidad , Estudios Retrospectivos , Análisis de Supervivencia , Tiempo de Tratamiento , Acondicionamiento Pretrasplante , Trasplante Autólogo , Resultado del TratamientoRESUMEN
OBJECTIVES: We studied the short- and long-term effects of imatinib in hospitalized COVID-19 patients. METHODS: Participants were randomized to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400 mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomized trials studying imatinib for 30-day mortality in hospitalized COVID-19 patients. RESULTS: We randomized 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year, and in SoC, 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47-3.90). At 1 year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78-1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32-1.63; low certainty evidence). CONCLUSIONS: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalized COVID-19 patients.
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Tratamiento Farmacológico de COVID-19 , COVID-19 , Hospitalización , Mesilato de Imatinib , Calidad de Vida , SARS-CoV-2 , Humanos , Mesilato de Imatinib/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , COVID-19/mortalidad , Hospitalización/estadística & datos numéricos , Anciano , Resultado del Tratamiento , AdultoRESUMEN
Biologic and clinical observations suggest that combining imatinib with IFN-α may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission either to receive a combination of pegylated IFN-α2b (Peg-IFN-α2b) 50 µg weekly and imatinib 400 mg daily (n = 56) or to receive imatinib 400 mg daily monotherapy (n = 56). The primary endpoint was the major molecular response (MMR) rate at 12 months after randomization. In both arms, 4 patients (7%) discontinued imatinib treatment (1 because of blastic transformation in imatinib arm). In addition, in the combination arm, 34 patients (61%) discontinued Peg-IFN-α2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg-IFN-α2b arm (82%) compared with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg-IFN-α2b treatment (< 12-week MMR rate 67%, > 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg-IFN-α2b to imatinib markedly increased the MMR rate at 12 months of therapy. Lower doses of Peg-IFN-α2b may enhance tolerability while retaining efficacy and could be considered in future protocols with curative intent.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Interferón-alfa/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva , Piperazinas/uso terapéutico , Polietilenglicoles/uso terapéutico , Pirimidinas/uso terapéutico , Inducción de Remisión/métodos , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Benzamidas , Biomarcadores/análisis , Cálculo de Dosificación de Drogas , Femenino , Proteínas de Fusión bcr-abl/análisis , Proteínas de Fusión bcr-abl/biosíntesis , Humanos , Mesilato de Imatinib , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Reacción en Cadena de la Polimerasa , Proteínas Tirosina Quinasas/análisis , Proteínas Tirosina Quinasas/biosíntesis , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Factores de Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVE: Infections and graft-versus-host disease (GVHD) are the main causes of transplant-related mortality (TRM) of patients undergoing allo-SCT. The role of iron overload (IO) has been debated in this context. Studies, performed with non-specific surrogate markers of iron, suggest that IO predicts poor outcome after allo-SCT. METHODS: In this prospective study, we quantified pretransplant IO with MRI-based hepatic iron concentration (HIC) measurement; the degree of IO was used to predict infections, GVHD, and mortality after allo-SCT. Logistic univariate, multivariate, and Cox's regression analyses were performed. RESULTS: Iron overload was present in 78% of the patients (HIC>36 µmol/g). The median HIC was 98 µmol/g (range 5-348). There were no cases of cardiac iron excess. IO was significantly associated with severe infections during the early post-transplant period (for every 10 µmol/g increase OR: 1.15, 95% CI 1.05-1.26, P = 0.003). The odds for severe infections increased 6.5- (>125 µmol/g OR: 6.5, P = 0.013) to 14-fold (>269 µmol/g OR: 14.1, P = 0.040) with increasing HIC. IO was found to be associated with reduced risk of acute and chronic GVHD. Although TRM was due to infection-related deaths, IO was not associated with TRM or OS. CONCLUSION: Pretransplant IO, measured with a direct MRI-based measurement, predicts severe infections in the early post-transplant period.
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Sobrecarga de Hierro/diagnóstico , Trasplante de Células Madre/métodos , Adulto , Anciano , Femenino , Enfermedad Injerto contra Huésped , Humanos , Hierro/metabolismo , Sobrecarga de Hierro/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: The Puumala virus (PUUV) is a hantavirus that causes hemorrhagic fever with renal syndrome. Studies showing an increased risk of lymphoid malignancies after hantavirus infection, together with the observation that PUUV infects B cells, motivated us to study the risk of lymphoid malignancies after PUUV infection. METHODS: We linked data from the Finnish Cancer Registry and National Infectious Diseases Register for 2009-2019. We used a time-dependent Cox regression model to evaluate the hazard of the lymphoid malignancies grouped according to the HAEMACARE classification. RESULTS: We identified 68 cases of lymphoid malignancies after PUUV infection among 16,075 PUUV-infected individuals during 61,114,826 person-years of observation. A total of 10 cases occurred within 3-<12 months and 38 within 1-<5 years after PUUV infection, and the risk of lymphoid malignancies increased with hazard ratios (HRs) of 2.0 (95% confidence interval [CI], 1.1-3.7) and 1.6 (95% CI, 1.2-2.3), respectively. The group of mature B cell neoplasms showed an increased risk 3-<12 months and 1-<5 years after PUUV infection, HR 2.2 (95% CI, 1.2-4.3) and HR 1.8 (95% CI, 1.3-2.5), respectively. CONCLUSION: PUUV infection is associated with lymphoid malignancies in the Finnish population, supporting the earlier studies. Further research is required to understand the pathophysiological mechanisms behind this association.
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Infecciones por Hantavirus , Fiebre Hemorrágica con Síndrome Renal , Neoplasias , Virus Puumala , Humanos , Fiebre Hemorrágica con Síndrome Renal/epidemiología , Finlandia/epidemiología , Estudios de Cohortes , Estudios Retrospectivos , Infecciones por Hantavirus/epidemiología , Neoplasias/etiología , Neoplasias/complicacionesRESUMEN
Myeloma-dependent cast nephropathy (MCN) is a medical emergency where prompt medical intervention is essential to rescue the kidneys from irreversible damage and the patient from lifelong dialysis. Evidence of the benefit of plasma exchange in removing serum free light chains (sFLC) has been controversial [1,2]. According to our recent experience, high cut-off hemodialysis (HCOD) with specially designed dialyzers reduces the level of sFLC concentration within hours and improves renal function in MCN in the long term when combined with effective bortezomib-based chemotherapy.
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Lesión Renal Aguda/terapia , Antineoplásicos/uso terapéutico , Ácidos Borónicos/uso terapéutico , Mieloma Múltiple/complicaciones , Inhibidores de Proteasas/uso terapéutico , Pirazinas/uso terapéutico , Diálisis Renal/métodos , Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Anciano , Anciano de 80 o más Años , Bortezomib , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/cirugía , Diálisis Renal/instrumentación , Trasplante de Células Madre , Trasplante Autólogo , Resultado del TratamientoRESUMEN
The 23-valent pneumococcal polysaccharide vaccine (PPV23) given alone is ineffective in patients with chronic lymphocytic leukemia (CLL) and better antibody response is achieved with pneumococcal conjugate vaccines (PCVs). In this study, we determine whether CLL patients would achieve a significant antibody response and broaden their serotype coverage against invasive pneumococcal disease (IPD) with PPV23 given five years after the 7-valent conjugate vaccine (PCV7). A total of 24 patients with CLL and eight controls were vaccinated with PPV23 five years after PCV7. Blood samples for evaluation of antibody response to PCV7 serotypes and PPV23 serotypes 5 and 7 were taken before vaccination and one month after it. Post-vaccination samples were available from 20 patients. IgG antibodies were measured with ELISA. Antibody concentrations after PPV23 were significantly lower in CLL patients for six of the PCV7 serotypes and for both PPV23 serotypes. Only 10% to 15% of CLL patients achieved an antibody response suggested to be protective against IPD. Hence, PCV7 given five years before PPV23 did not improve antibody response in patients with CLL. Based on our results, PPV23 given after a PCV primer is not useful against IPD in CLL patients.
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Anticuerpos Antibacterianos/sangre , Vacuna Neumocócica Conjugada Heptavalente/inmunología , Inmunización Secundaria , Leucemia Linfocítica Crónica de Células B/inmunología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Vacunas Conjugadas/inmunologíaRESUMEN
As novel immunological treatments are gaining a foothold in the treatment of acute lymphoblastic leukemia (ALL), it is elemental to examine ALL immunobiology in more detail. We used multiplexed immunohistochemistry (mIHC) to study the immune contexture in adult precursor B cell ALL bone marrow (BM). In addition, we developed a multivariate risk prediction model that stratified a poor survival group based on clinical parameters and mIHC data. We analyzed BM biopsy samples of ALL patients (n = 52) and healthy controls (n = 14) using mIHC with 30 different immunophenotype markers and computerized image analysis. In ALL BM, the proportions of M1-like macrophages, granzyme B+CD57+CD8+ T cells, and CD27+ T cells were decreased, whereas the proportions of myeloid-derived suppressor cells and M2-like macrophages were increased. Also, the expression of checkpoint molecules PD1 and CTLA4 was elevated. In the multivariate model, age, platelet count, and the proportion of PD1+TIM3+ double-positive CD4+ T cells differentiated a poor survival group. These results were validated by flow cytometry in a separate cohort (n = 31). In conclusion, the immune cell contexture in ALL BM differs from healthy controls. CD4+PD1+TIM3+ T cells were independent predictors of poor outcome in our multivariate risk model, suggesting that PD1 might serve as an attractive immuno-oncological target in B-ALL.
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Médula Ósea/inmunología , Linfocitos T CD8-positivos/inmunología , Trasplante de Células Madre Hematopoyéticas , Macrófagos/inmunología , Células Supresoras de Origen Mieloide/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Microambiente Tumoral/inmunología , Adolescente , Adulto , Anciano , Antígeno CTLA-4 , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
Patients with chronic lymphocytic leukemia (CLL) are at a high risk for infections caused by Streptococcus pneumoniae. A pneumococcal conjugate vaccine (PCV) can induce a significant antibody response for some CLL patients. In this study we investigated antibody persistence after PCV7 in patients with CLL. The study material comprised 24 patients with CLL and 8 immunocompetent controls. The median antibody concentrations five years after PCV7 were lower for six pneumococcal serotypes in patients with CLL compared to controls, but the difference was not statistically significant. Depending on the serotype, the percentage of the CLL patients with antibody levels suggested to provide protection against invasive pneumococcal disease (IPD) varied from 29 to 71% five years after vaccination. This data suggests that PCV could result in antibody persistence at least five years in CLL patients.
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Anticuerpos Antibacterianos/sangre , Vacuna Neumocócica Conjugada Heptavalente/inmunología , Leucemia Linfocítica Crónica de Células B/complicaciones , Infecciones Neumocócicas/prevención & control , Streptococcus pneumoniae/inmunología , Cuidados Posteriores , Anciano , Anciano de 80 o más Años , Femenino , Vacuna Neumocócica Conjugada Heptavalente/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
Outcomes for patients with multiple myeloma (MM) have improved with the advent of novel therapies, however, real-world evidence of outcomes in clinical practice is scarce. We conducted a multi-center registry study to build a reliable picture of treatment and patient outcomes in Finland. The aim of this study was also to understand any methodological challenges in assessing treatment outcomes using disease registry data. METHODS: We carried out a retrospective, observational study using data from the national Finnish Hematology Registry (FHR) to provide real-world evidence of outcomes for all adult patients diagnosed with and treated for MM between 2009-2013 at one of the six regional hospitals, with at least six months of recorded follow-up. Patients were identified within the FHR by applying eligibility criteria of a diagnosis of MM and verifiable records of medical treatment and lines of treatment during the study period. Patients receiving allogenic stem cell transplantation were excluded from the cohort, as were individuals who only had monoclonal gammopathy of undetermined significance diagnosis and patients who had not initiated treatment during this period. Kaplan Meier curves were used to calculate overall survival and time to next treatment. Stratification was carried out by drug status (conventional/novel) and by autologous stem cell transplant (ASCT) status. RESULTS: A total of 321 patients met the inclusion criteria and were included in this study. Overall survival (OS) was longest in patients who received first-line novel therapy and ASCT (median not reached during 60-month follow-up) versus 46.2 months for novel first-line therapy without ASCT and 25.6 months for first-line conventional therapy without ASCT. Similarly, median time to next treatment were 33.9 months, 12.6 months and 7.8 months, respectively. CONCLUSIONS: The adoption of novel treatments in MM in Finland has had substantial impact on patient outcomes. Given the reality of complex treatment combinations for MM and relatively low patient numbers, assessing individual treatment effectiveness will require substantial cohort sizes and advanced, collaborative analytics on an international scale.
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Antineoplásicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Mieloma Múltiple/terapia , Anciano , Anciano de 80 o más Años , Femenino , Finlandia , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Sistema de Registros , Estudios Retrospectivos , Trasplante Autólogo , Resultado del TratamientoRESUMEN
Valproic acid (VPA), an inhibitor of histone deacetylases, inhibits the growth of leukemia cells and induces their differentiation in vitro. In the present study, VPA in combination with two differentiating agents, 13-cis retinoic acid and 1,25-dihydroxyvitamin D3, was given to 19 previously untreated patients with MDS or CMML. Eight patients had to discontinue treatment before week 16 due to toxicity. According to international working group criteria, three patients (16%) responded to treatment. No correlation between VPA serum level, histone acetylation or clinical response was observed.
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Calcitriol/uso terapéutico , Isotretinoína/uso terapéutico , Síndromes Mielodisplásicos/tratamiento farmacológico , Ácido Valproico/uso terapéutico , Acetilación/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Calcitriol/administración & dosificación , Calcitriol/efectos adversos , Queilitis/inducido químicamente , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Quimioterapia Combinada , Fatiga/inducido químicamente , Histonas/metabolismo , Humanos , Isotretinoína/administración & dosificación , Isotretinoína/efectos adversos , Persona de Mediana Edad , Neumonía/inducido químicamente , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Resultado del Tratamiento , Ácido Valproico/administración & dosificación , Ácido Valproico/efectos adversosRESUMEN
Cerebral venous thrombosis (CVT) covers up to a third of all venous thromboses (VTs) detected in patients with acute lymphoblastic leukemia (ALL). It usually hampers patients' lives and may also endanger efficient leukemia treatment. Although many factors have been suggested to account for an elevated risk of VTs in patients with ALL, there still is a lack of studies focusing on CVTs and especially in the setting of adult ALL patients. We studied in our retrospective population-based cohort the occurrence, characteristics, as well as risk factors for VTs in 186 consecutively diagnosed Finnish adult ALL patients treated with a national pediatric-inspired treatment protocol ALL2000. In the risk factor analyses for VTs we found a distinction of the characteristics of the patients acquiring CVT from those with other kinds of VTs or without thrombosis. In contrast to previous studies we were also able to compare the effects of asparaginase in relation to CVT occurrence. Notably, more than half of the CVTs were diagnosed prior the administration of asparaginase which accentuates the role of other risk factors on the pathophysiology of CVT compared to truncal or central venous line (CVL) VTs in adult ALL patients.
Asunto(s)
Asparaginasa/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Trombosis de la Vena/epidemiología , Adolescente , Adulto , Anciano , Susceptibilidad a Enfermedades , Femenino , Finlandia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Infections greatly influence the outcome of acute myeloid leukemia (AML) patients receiving intensive treatment. The aim of this study was to establish the incidence, microbial etiology, risk factors and prognosis of bloodstream infections (BSIs) in patients with AML and compare the results with the previous treatment protocol (AML-92). METHODS: Registery data were gathered prospectively from 357 patients aged 16-65 years recruited on the AML-2003 treatment protocol between November 2003 and November 2011 during different treatment cycles. RESULTS: Blood culture data were available on 977 treatment episodes, in which there were 503 BSIs (51%). The overall incidence rate (IR) for BSIs (per 1000 hospital days) was 16.7. Twenty patients (5.6%) died due to an infection and 16 of them (80%) had a BSI. The most commonly detected microbes (polymicrobial episodes included) in blood cultures were coagulase-negative staphylococci (CoNS, 24.7%), viridans group streptococci (VGS, 19.1%), enterococci (13.9%) and Enterobacteriacae group (25.9%). The etiology of BSIs varied greatly from treatment cycle to cycle. CONCLUSIONS: Enterococcal BSIs have increased compared to our previous treatment protocol, and they represent significant pathogens in blood cultures. Infection-related mortality has decreased despite the increase in the IR of BSIs. Enterococci seem to be an increasingly prominent pathogen underlying BSIs in the AML patients, especially during induction therapy (20%).
Asunto(s)
Bacteriemia/epidemiología , Bacteriemia/etiología , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Anciano , Bacteriemia/microbiología , Bacteriemia/terapia , Bacterias/aislamiento & purificación , Cultivo de Sangre , Femenino , Finlandia/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Adulto JovenRESUMEN
The baseline national invasive pneumococcal disease (IPD) incidence rate, serotype distribution and serotype coverage of pneumococcal vaccines were evaluated in patients with Hodgkin's and non-Hodgkin's lymphomas, myeloma and leukaemia within 1 year after haematological diagnosis during 1995-2002, before introduction of pneumococcal conjugate vaccines. Pneumococcal serotype distribution among these patients was different from serotypes causing IPD in the general population. The serotype coverages of PCV13 and PPSV23 were 57% and 64%, respectively, lower than in the general population. This reflects a higher predisposition to IPD in vaccinated patients with haematological malignancies and possibly less benefit of herd immunity gained with the wide use of pneumococcal conjugate vaccines in the general population. This data will be useful as a baseline for determining the future role of adult PCV vaccination in these patient groups.