Improving the diagnosis of myelodysplastic syndrome by red blood cell parameters

Purpose To investigate the value of red blood cell parameters in Myelodysplastic syndrome (MDS) diagnosis and their relations to MDS subtypes and risk groups. Methods The red blood cell parameter [mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW)] levels [203 MDS, 99 aplastic anemia (AA), 145 megaloblastic anemia (MA)] were collected from a single-center retrospective cohort. The cut-off values, area under the receiver operating characteristic curve (ROC) curve (AUC), sensitivity and specificity of the four parameters were calculated from the ROC. Furthermore, Kruskal–Wallis test and Dunn’s Test were performed to determine erythrocyte parameters in different subtypes and prognostic risks MDS. Results There are significant statistic differences in RDW (P < 0.001), MCH (P = 0.036) and MCHC (P < 0.001) (MDS vs AA); RDW (P = 0.009), MCV (P < 0.001), MCH (P < 0.001) and MCHC (P = 0.001) (MDS vs MA); MCV (P = 0.011) and MCH (P = 0.008) (higher-risk MDS vs lower-risk MDS). Between MDS and MA, the area under the receiver operating characteristic curve (ROC) curve (AUC) values of MCV, MCH, MCHC, RDW were 0.846, 0.855, 0.617, and 0.593. Between MDS and AA, the AUC values of MCH, MCHC, RDW were 0.609, 0.671, and 0.662, respectively. Conclusions The red blood cell parameters contribute to the differential diagnosis of MDS, AA and MA and are related to MDS subtypes and risk groups (AU)

A research review of experimental animal models with myelodysplastic syndrome

Myelodysplastic syndrome (MDS) consists of a group of hematologic tumors that are derived from the clonal proliferation of hematopoietic stem cells, featuring abnormal hematopoietic cell development and ineffective hematopoiesis. Animal models are an important scientific research platform that has been widely applied in the research of human diseases, especially tumors. Animal models with MDS can simulate characteristic human genetic variations and tumor phenotypes. They also provide a reliable platform for the exploration of the pathogenesis and diagnostic markers of MDS as well as for a drug efficacy evaluation. This paper reviews the research status of three animal models and a new spontaneous mouse model with MDS (AU)

Impact of risk scores in outcome of patients with myeloid neoplasms after allogeneic stem cell transplant / Impacto de las puntaciones del riesgo en los resultados de los pacientes con neoplasias mieloides tras el trasplante alogénico de células madre

Background:The main causes of failure of allogeneic hematopoietic stem cell transplantation (allo-transplant) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are relapse and transplant-related mortality. Different scores have been designed to predict the prognosis of these patients. The objective of this study was to assess which score or combination has better outcome predictive capacity.Methods:Retrospective analysis of patients with AML and MDS who received a first peripheral blood allo-transplant in a single center, between December 2001 and October 2019. Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), European Group for Blood and Marrow Transplantation (EBMT) and Disease Risk Index (DRI) scores were calculated. For each score and for the HCT-CI/DRI and HCT-CI/EBMT combinations, overall survival (OS), cumulative incidence of relapse (CIR), non-relapse-related mortality (NRM), and graft versus host disease-free relapse-free survival (GRFS) were analyzed.Results:175 patients were evaluated. With a median (range) follow-up of 3.96 (0.32–17.22) years, the 5-year probabilities (95% CI) of OS, CIR, NRM, and GRFS were 36% (28%–44%), 28% (21%–35%), 38% (30%–46%) and 24% (17%–31%), respectively. For OS, only the DRI score selected two groups with statistically significant differences (DRI 0–1: 41% vs. DRI ≥2: 24%; p=0.011). The combination of DRI 0–1 and HCT-CI 0–2 showed OS probabilities of 45% vs. 26% for those with DRI 0–1 and HCT-CI ≥3; p=0.041.Conclusions:In patients with AML and MDS submitted to allo-transplant, the combination of HCT-CI and DRI scores provided the best stratification for OS. (AU)

Antecedentes:Las principales causas de fallo del trasplante alogénico de células madre hematopoyéticas (alotrasplante) en pacientes con leucemia mieloide aguda (LMA) y síndromes mielodisplásicos (SMD) son las recaídas y la mortalidad debida al trasplante. Se han diseñado diferentes puntuaciones para predecir el pronóstico de dichos pacientes. El objetivo de este estudio fue evaluar qué puntuación o combinación tiene la mejor capacidad predictiva del resultado.Métodos:Análisis retrospectivo de pacientes con LMA y SMD que recibieron un primer alotrasplante de sangre periférica en un único centro, entre diciembre de 2001 y octubre de 2019. Se calcularon las puntuaciones del Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), del European Group for Blood and Marrow Transplantation (EBMT) y del Disease Risk Index (DRI). Para cada puntuación y para las combinaciones HCT-CI/DRI y HCT-CI/EBMT se analizaron la supervivencia global (SG), la incidencia acumulada de recaídas (CIR), la mortalidad no relativa a las recaídas (NRM) y la supervivencia libre de recaídas y libre de enfermedad de injerto versus huésped (GRFS).Resultados:Se evaluaron 175 pacientes. Con un seguimiento medio (rango) de 3,96 (0,32-17,22) años, las probabilidades a 5años (IC95%) de SG, CIR, NRM y GRFS fueron del 36% (28-44), del 28% (21-35), del 38% (30-46) y del 24% (17-31), respectivamente. Para la SG, solo la puntuación DRI seleccionó dos grupos con diferencias estadísticamente significativas (DRI 0-1: 41% vs. DRI≥2: 24%; p=0,011). La combinación de DRI 0-1 y HCT-CI 0-2 reflejó probabilidades de SG del 45% vs. 26% para los pacientes con DRI 0-1 y HCT-CI≥3 (p=0,041).Conclusiones:En los pacientes con LMA y SMD sometidos a alotrasplante la combinación de las puntuaciones HCT-CI y DRI proporcionó la mejor estratificación para la SG. (AU)

Resultados del trasplante de progenitores hematopoyéticos de donante no emparentado con o sin globulina antitimocítica como profilaxis de la enfermedad del injerto contra receptor en pacientes con leucemia aguda y síndrome mielodisplásico / Outcomes of unrelated donor stem cell transplantation with or without anti-thymocyte globulin used as graft-versus-host disease prophylaxis in patients with acute leukaemia and myelodysplastic syndrome

Fundamento y objetivo: La enfermedad del injerto contra el receptor (EICR) y las infecciones son complicaciones del trasplante alogénico de progenitores hematopoyéticos (alo-TPH). La globulina antitimocítica (ATG) es una estrategia empleada para la profilaxis de la EICR. Este estudio analiza los resultados y la frecuencia de infecciones en función del uso de ATG, después de un alo-TPH de donante no emparentado (DNE) en pacientes con leucemia aguda y síndrome mielodisplásico.Pacientes y métodoEstudio retrospectivo de pacientes que recibieron un alo-TPH de DNE entre diciembre de 2007 y abril de 2019. Se compararon los principales resultados en función del uso de ATG.ResultadosSe incluyó a 66 pacientes. No se encontraron diferencias significativas en el grupo ATG (n=50) frente al no ATG (n=16) en supervivencia global, incidencia acumulada de recaída, mortalidad no debida a recaída o incidencia acumulada de EICR aguda o crónica. Hubo mayor frecuencia de infecciones en el grupo ATG (60 frente a 19%; p=0,004).ConclusionesEn este estudio no se demostró diferencia en los principales resultados del alo-TPH en función del uso de ATG, pero hubo más infecciones en el grupo que recibió ATG. (AU)

Background and purpose: Graft-versus-host disease (GVHD) and infections are complications after allogeneic stem cell transplantation (alloSCT). Anti-thymocyte globulin (ATG) is a strategy used as prophylaxis for GVHD. The study analyses the outcomes and frequency of infections with or without ATG after an unrelated donor alloSCT in patients with acute leukaemia and myelodysplastic syndrome.Patients and methodsRetrospective study of patients receiving an unrelated donor alloSCT between December 2007 and April 2019. The main outcomes were analysed according to use or not of ATG.ResultsSixty-six patients were included. No significant differences were found between the ATG group (n=50) vs. no-ATG group (n=16) in overall survival, cumulative incidence of relapse, cumulative incidence of non-relapse mortality or cumulative incidence of acute GVHD or chronic GVHD. There was a greater frequency of infections in the ATG group (60 vs. 19%, P=.004).ConclusionsIn this study, no differences were shown in the main outcomes of alloSCT based on the use of ATG, although more infections were documented in the ATG group. (AU)

Dermatosis neutrofílica y síndrome mielodisplásico / Neutrophilic dermatosis and myelodysplastic syndrome

No disponible

Síndrome de Sweet mielodisplásico corticodependiente. A propósito de un caso / Corticosteroid-dependent myelodysplastic Sweet's syndrome. Presentation of a case

Fundamento y objetivo: El síndrome de Sweet o dermatosis neutrofílica febril aguda es una enfermedad inflamatoria infrecuente de fisiopatología desconocida, aunque las evidencias clínicas y bioquímicas sugieren que las citocinas tienen un papel importante en su etiopatogenia. Se distinguen 5 grupos etiológicos: idiopático, parainflamatorio, secundario a fármacos, asociado a embarazo y paraneoplásico. Este último grupo representa el 20% de los casos, asociados el 85% de ellos a neoplasias hematológicas y el 15% a tumores sólidos. Paciente: Se presenta el caso de un paciente afecto de síndrome de Sweet con afectación dermatológica atípica, asociado a un síndrome mielodisplásico y también a un síndrome de Cushing iatrogénico secundario a altas dosis de corticoides cuya evolución fue desfavorable. Resultados: Positividad de los reactantes de fase aguda (RFA) durante los brotes, destacando la elevación precoz de la interleucina 6 (IL-6) seguida del seroamiloide A (SAA) y proteína C reactiva (PCR), encontrándose diferencias estadísticamente significativas (p<0,05) entre la PCR y el SAA. Conclusiones: Un síndrome de Sweet en un varón con múltiples recaídas y localización dermatológica no clásica, cuando se asocia a alteraciones hematológicas, con un incremento de los RFA y elevación precoz de la IL-6 debe orientar el diagnóstico clínico hacia un origen paraneoplásico y hematológico

Background and objective: Sweet's syndrome or acute febrile neutrophilic dermatosis is a rare inflammatory disease of unknown pathophysiology, although clinical and biochemical evidence suggests that cytokines play an important role in its aetiopathogenesis. It is classified into five groups: idiopathic, para-inflammatory, secondary to drugs, associated with pregnancy, and para-neoplastic in 20% of cases, with 85% of these linked to haematological disorders, and 15% to solid tumours. Patient: A report is presented on a patient with Sweet's Syndrome with atypical dermatological involvement, associated with myelodysplastic syndrome, and iatrogenic Cushing's syndrome secondary to high-doses of corticosteroids, with an unfavorable outcome. Results: Acute phase reactants (APR) were increased during the outbreaks, with the early elevation of interleukin 6 (IL6) being highlighted, followed by serum amyloid A (SAA) and C-reactive protein (CRP), with statistically significant differences (P<.05) between CRP and SAA. Conclusions: A Sweet's syndrome in a male with multiple relapses and a non-classical dermatological location, associated haematological abnormalities, and an increase in APR with early elevation of IL6, should lead to a clinical diagnosis of paraneoplastic and haematological origin

Necrosis retiniana como manifestación de aspergilosis invasiva en un paciente tratado con ruxolitinib / Invasive aspergillosis manifesting as retinal necrosis in a patient treated with ruxolitinib

Varón de 30 años de edad con leucemia mieloblástica aguda y síndrome mielodisplásico secundario que desarrolló una enfermedad injerto contra huésped. El paciente fue tratado con ruxolitinib, un inhibidor de la Janus quinasa. A los 3 meses de haber iniciado el tratamiento se produjo una necrosis retiniana por Aspergillus, sin respuesta al tratamiento. El tratamiento con inhibidores de la Janus quinasa favorecería un aumento en la incidencia de infecciones oportunistas. El uso de estos fármacos podría dar lugar a una menor eficacia de los tratamientos empleados

A 30 year-old man with acute myeloblastic leukaemia and secondary myelodysplastic syndrome developed graft-versus-host disease. The patient was treated with ruxolitinib. After being treated for 3 months with ruxolitinib, an inhibitor of Janus kinase, he developed Aspergillus retinal necrosis resistant to common treatment. Treatment with Janus kinase inhibitors may lead to an increased incidence of opportunistic infections. Janus kinase inhibitor administration may result in poor treatment efficacy

Agentes estimuladores de la eritropoyetina: revisión bibliográfica de los usos e indicaciones en enfermedad avanzada oncológica y no oncológica en el anciano / Erythropoiesis stimulating agents: Literature review of uses and indications in advanced oncological and non-oncological disease in the elderly

El objetivo de este artículo es revisar las posibles indicaciones y controversias sobre los usos más frecuentes de los agentes estimuladores de la eritropoyetina (AEE) en el tratamiento de la anemia de los pacientes ancianos, con enfermedad oncológica y no oncológica avanzada. Para ello, hemos realizado una revisión sistemática en Pubmed, de artículos publicados desde 1985 hasta septiembre del 2016. Hemos realizado también la revisión de las principales guías de consenso españolas, europeas y americanas, en relación con el manejo de la anemia relacionada con las enfermedades reseñadas en el artículo. Hemos encontrado que existen barreras para su uso en pacientes ancianos con enfermedad avanzada, sobre todo por la falta de uniformidad y consenso en las recomendaciones, y por la ausencia de ensayos prospectivos a gran escala para explorar la eficacia de los AEE en esta población. Parece haber consenso en la utilización en los pacientes con enfermedad renal crónica avanzada, en pacientes con tumores no mieloides, en tratamiento con quimiterapia con intención no curativa, y en pacientes con síndrome mielodisplásico, todavía respondedores, para espaciar el soporte transfusional. En el resto, debe individualizarse, ya que el riesgo de mortalidad y morbilidad cardiovascular está claramente aumentado. No debe ser la solución para tratar la anemia, en casos de urgencia o de necesidad transfusional a corto plazo, muchas veces presentes en este paciente

The aim of this article is to review possible indications and controversies about the most frequent uses of ESAs in the treatment of anaemia in elderly patients with oncological and non-oncological diseases. Using PubMed a systematic review was carried out on articles published from 1985 to September 2016, as well as a review of the main Spanish, European, and American consensus guidelines on each of the following diseases in which could pose the treatment of anaemia associated with ESA. A review was also carried out on the main Spanish, European and American consensus guidelines regarding the management of anaemia related to the diseases outlined in this article. It was found that there are limitations of its use in elderly patients with advanced disease, mainly due to the lack of uniformity and consensus in the recommendations, and the absence of large-scale prospective trials to determine the effectiveness of ESA in this population. There seems to be consensus in the use in patients with advanced chronic kidney disease, individualised in patients with non-myeloid cancer on treatment without curative intent, and in patients with myelodysplastic syndrome, still responders to space transfusional support. In the remainder, it should be individualised, since the risk of mortality and cardioembolic morbidity is clearly increased. It should not be the solution to treat anaemia, in cases of urgency or short-term transfusional need, which are often present in these patients

Rentabilidad diagnóstica de la resonancia magnética lumbosacra solicitada desde las consultas de urología pediátrica / Diagnostic yield of lumbosacral magnetic resonance imaging requested by paediatric urology consultations

Objetivos: En series históricas, la rentabilidad diagnóstica de la resonancia magnética lumbosacra para descartar disrafismo espinal oculto (o mielodisplasia oculta), solicitada desde urología pediátrica oscila entre el 2 y 15%. El objetivo del estudio es definir nuestra rentabilidad en niños con síntomas miccionales, y definir variables que aumenten la posibilidad de encontrar disrafismo espinal oculto. Pacientes y métodos: Selección de pacientes con disfunciones miccionales a los que se solicitó resonancia magnética desde las consultas de urología pediátrica, por persistencia de síntomas tras tratamiento, disfunción de vaciado, o por otros hallazgos clínicos o urodinámicos. Se analizaron variables clínicas (ITU, fugas diurnas, enuresis, disfunción de vaciado, urgencia, ecografía renal, radiografía lumbosacra, antecedentes de retención aguda de orina, estigmas cutáneos, mialgias) y urodinámicas (hiperactividad o arreflexia, micción disfuncional, patrón interrumpido, valor de acomodación y flujo máximo). Análisis univariante con SPSS 20.0 Resultados: Analizamos a 21 pacientes en el periodo 2011-2015. Mediana de edad: 6 años (3-10). Tres pacientes (14,3%) presentaron disrafismo espinal oculto: un lipoma raquídeo, un filum lipomatoso y un síndrome de regresión caudal con estenosis de canal. Las variables con diferencia estadísticamente significativa fueron las mialgias y el antecedente de retención aguda de orina (66,7 vs. 5,6%; p = 0,04; OR = 34; IC95%: 1,5-781 para ambas variables). Conclusiones: La rentabilidad diagnóstica de la resonancia magnética solicitada a niños con disfunciones miccionales sin estigmas cutáneos ni alteraciones neuroortopédicas es baja, aunque no desdeñable. En este grupo, los pacientes con antecedentes de retención aguda de orina y/dolor muscular (dolor, «calambres») pueden presentar una rentabilidad diagnóstica o valor predictivo positivo mayor

Objectives: In the historical series, the diagnostic yield of lumbosacral magnetic resonance imaging to rule out occult spinal dysraphism (or occult myelodysplasia), requested by paediatric urology, ranged from 2% to 15%. The aim of this study was to define our cost-effectiveness in children with urinary symptoms and to define endpoints that increase the possibility of finding occult spinal dysraphism. Patients and methods: A screening was conducted on patients with urinary dysfunction for whom an magnetic resonance imaging was requested by the paediatric urology clinic, for persistent symptoms after treatment, voiding dysfunction or other clinical or urodynamic findings. We analysed clinical (UTI, daytime leaks, enuresis, voiding dysfunction, urgency, renal ultrasonography, lumbosacral radiography, history of acute urine retention, skin stigma and myalgia) and urodynamic endpoints (hyperactivity or areflexia, voiding dysfunction, interrupted pattern, accommodation value and maximum flow). A univariate analysis was conducted with SPSS 20.0. Results: We analysed 21 patients during the period 2011-2015. The median age was 6 years (3-10). Three patients (14.3%) had occult spinal dysraphism: one spinal lipoma, one filum lipomatosus and one caudal regression syndrome with channel stenosis. The endpoints with statistically significant differences were the myalgias and the history of acute urine retention (66.7% vs. 5.6%, P = .04; OR = 34; 95%CI: 1.5-781 for both endpoints). Conclusions: The diagnostic yield of magnetic resonance imaging requested for children with urinary dysfunctions without skin stigma or neuro-orthopaedic abnormalities is low, although nonnegligible. In this group, the patients with a history of acute urine retention and muscle pain (pain, «cramps») can experience a greater diagnostic yield or positive predictive value

Aplicabilidad y coste-efectividad de la administración de azacitidina en régimen domiciliario / Feasibility and cost-effectiveness of at home azacitidine administration

No disponible

MicroRNAs as prognostic biomarker and relapse indicator in leukemia

Despite significant progress in the treatment of different types of leukemia, relapse remains a challenging clinical problem that is observed in a number of patients who are often resistant to chemotherapy and exhibit multi-drug resistance. Identification of new functional biomarkers, including microRNAs, is essential to determine prognosis and relapse at the time of diagnosis. The aim of this study was to detect the specific microRNAs involved in predicting relapse or progression in acute and chronic leukemias, as well as their relationship with overall survival (OS) and relapse-free survival (RFS). The relevant literature was identified through a PubMed and Scholar search (2008-2016) of English-language papers using the terms Leukemia, microRNAs, survival and relapse. Different leukemia types and subtypes show specific microRNA expression profile and different changes, which can be useful in the differentiation between leukemias and evaluation of relapse at the time of diagnosis. Altered microRNA expression profiles can turn these molecules into oncogenes or tumor suppressors, which affect the expression of relapse-related genes. Therefore, monitoring of specific microRNA expression profiles from diagnosis and during follow-up of patients can contribute to the assessment of outcome and determination of relapse and prognosis of leukemic patients (AU)

No disponible

Dermatitis granulomatosa como manifestación cutánea de trastornos hematológicos: primer caso asociado a policitemia vera y un nuevo caso asociado a mielodisplasia / Granulomatous Dermatitis as a Cutaneous Manifestation of Hematologic Disorders: The First Case Associated With Polycythemia Vera and a New Case Associated With Myelodysplasia

Las dermatitis de patrón granulomatoso se han relacionado con trastornos hematológicos, entre ellos los síndromes mielodisplásicos. En este artículo se describe el primer caso de dermatitis granulomatosa asociado a policitemia vera, en forma de grandes nódulos eritematosos simulando paniculitis, y el séptimo caso asociado a mielodisplasia, con placas eritematosas en cara y cuello que recordaban a una dermatosis neutrofílica. Consideramos de especial interés para el dermatólogo conocer esta dermatosis como manifestación no específica de diferentes trastornos hematológicos, y sugerimos la realización de un estudio complementario (hemograma) en el caso de que la clínica cutánea sea el comienzo. Del mismo modo, proponemos el término más amplio de dermatitis granulomatosas para denominarlas, puesto que, si bien las formas intersticiales son más numerosas en la literatura, también se han publicado casos más nodulares, y la importancia de su diagnóstico no radica en el subtipo sino en su relación con un trastorno subyacente

Granulomatous dermatitis has been associated with hematologic disorders, including the myelodysplastic syndromes. We describe the first case of granulomatous dermatitis associated with polycythemia vera, presenting as large erythematous nodules mimicking panniculitis. We also present the seventh case associated with myelodysplasia, with erythematous plaques on the face and neck, similar to a neutrophilic dermatosis. We consider it particularly interesting for dermatologists to be aware of this dermatosis as a nonspecific manifestation of various hematologic disorders. We suggest performing additional tests (complete blood count) to exclude the possibility that the skin manifestations are the initial sign of hematologic disease. Furthermore, we propose using the broader term, granulomatous dermatitis, to refer to these disorders as, although there are more reports of interstitial forms, cases with a more nodular presentation have also been published, and the importance of the diagnosis derives not from the subtype but from the relationship with an underlying disease