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Defining the transcriptomic identity of malignant cells is challenging in the absence of surface markers that distinguish cancer clones from one another, or from admixed non-neoplastic cells. To address this challenge, here we developed Genotyping of Transcriptomes (GoT), a method to integrate genotyping with high-throughput droplet-based single-cell RNA sequencing. We apply GoT to profile 38,290 CD34+ cells from patients with CALR-mutated myeloproliferative neoplasms to study how somatic mutations corrupt the complex process of human haematopoiesis. High-resolution mapping of malignant versus normal haematopoietic progenitors revealed an increasing fitness advantage with myeloid differentiation of cells with mutated CALR. We identified the unfolded protein response as a predominant outcome of CALR mutations, with a considerable dependency on cell identity, as well as upregulation of the NF-κB pathway specifically in uncommitted stem cells. We further extended the GoT toolkit to genotype multiple targets and loci that are distant from transcript ends. Together, these findings reveal that the transcriptional output of somatic mutations in myeloproliferative neoplasms is dependent on the native cell identity.
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Genotipo , Mutación , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/patología , Neoplasias/genética , Neoplasias/patología , Transcriptoma/genética , Animales , Antígenos CD34/metabolismo , Calreticulina/genética , Línea Celular , Proliferación Celular , Células Clonales/clasificación , Células Clonales/metabolismo , Células Clonales/patología , Endorribonucleasas/metabolismo , Hematopoyesis/genética , Células Madre Hematopoyéticas/clasificación , Células Madre Hematopoyéticas/metabolismo , Células Madre Hematopoyéticas/patología , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Ratones , Modelos Moleculares , Trastornos Mieloproliferativos/clasificación , FN-kappa B/metabolismo , Neoplasias/clasificación , Células Madre Neoplásicas/citología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Mielofibrosis Primaria/genética , Mielofibrosis Primaria/patología , Proteínas Serina-Treonina Quinasas/metabolismo , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , Respuesta de Proteína Desplegada/genéticaRESUMEN
Primary myelofibrosis (PMF) is the most aggressive of the myeloproliferative neoplasms and patients require greater attention and likely require earlier therapeutic intervention. Currently approved treatment options are limited in their selective suppression of clonal proliferation resulting from driver- and coexisting gene mutations. Janus kinase inhibitors are approved for symptomatic patients with higher-risk PMF. Additionally, most ongoing clinical studies focus on patients with higher-risk disease and/or high rates of transfusion dependency. Optimal treatment of early/lower-risk PMF remains to be identified and needs randomized clinical trial evaluations. Pegylated interferon alfa is recommended for symptomatic lower-risk PMF patients based on phase 2 non-randomized studies and expert opinion. Ropeginterferon alfa-2b (ropeg) is a new-generation pegylated interferon-based therapy with favorable pharmacokinetics and safety profiles, requiring less frequent injections than prior formulations. This randomized, double-blind, placebo-controlled phase 3 trial will assess its efficacy and safety in patients with "early/lower-risk PMF", defined as pre-fibrotic PMF or PMF at low or intermediate-1 risk according to Dynamic International Prognostic Scoring System-plus. Co-primary endpoints include clinically relevant complete hematologic response and symptom endpoint. Secondary endpoints include progression- or event-free survival, molecular response in driver or relevant coexisting gene mutations, bone marrow response, and safety. Disease progression and events are defined based on the International Working Group criteria and well-published reports. 150 eligible patients will be randomized in a 2:1 ratio to receive either ropeg or placebo. Blinded sample size re-estimation is designed. Ropeg will be administered subcutaneously with a tolerable, higher starting-dose regimen. The study will provide important data for the treatment of early/lower-risk PMF for which an anti-clonal, disease-modifying agent is highly needed.
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Erythropoietin (EPO) provides the major survival signal to maturing erythroid precursors (EPs) and is essential for terminal erythropoiesis. Nonetheless, progenitor cells can irreversibly commit to an erythroid fate well before EPO acts, risking inefficiency if these progenitors are unneeded to maintain red blood cell (RBC) counts. We identified a new modular organization of erythropoiesis and, for the first time, demonstrate that the pre-EPO module is coupled to late EPO-dependent erythropoiesis by megakaryocyte (Mk) signals. Disrupting megakaryocytic transforming growth factor ß1 (Tgfb1) disorganized hematopoiesis by expanding the pre-EPO pool of progenitor cells and consequently triggering significant apoptosis of EPO-dependent EPs. Similarly, pharmacologic blockade of TGFß signaling in normal mice boosted the pre-EPO module, leading to apoptosis of EPO-sensitive EPs. Subsequent treatment with low-dose EPO triggered robust RBC production in both models. This work reveals modular regulation of erythropoiesis and offers a new strategy for overcoming chronic anemias.
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Células Precursoras Eritroides/citología , Eritropoyesis/fisiología , Megacariocitos/citología , Factor de Crecimiento Transformador beta1/fisiología , Animales , Apoptosis/efectos de los fármacos , Médula Ósea/patología , Células Precursoras Eritroides/metabolismo , Eritropoyetina/farmacología , Técnicas de Inactivación de Genes , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Inmunofenotipificación , Células Progenitoras de Megacariocitos y Eritrocitos/citología , Células Progenitoras de Megacariocitos y Eritrocitos/metabolismo , Megacariocitos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Quimera por Radiación , Proteínas Recombinantes/farmacología , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/farmacologíaAsunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19 , Dexametasona , Neoplasias Hematológicas , Sistema de Registros , SARS-CoV-2 , Humanos , Dexametasona/uso terapéutico , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/tratamiento farmacológico , COVID-19/mortalidad , COVID-19/complicaciones , Masculino , Femenino , Anciano , Persona de Mediana Edad , SARS-CoV-2/aislamiento & purificación , Adulto , Anciano de 80 o más AñosRESUMEN
Patients with primary or secondary antiphospholipid syndrome (APS) have an increased risk of recurrent venous, arterial thrombosis and pregnancy complications. Therefore, determining thrombotic risk is important when individualizing antithrombotic therapy in patients with APS. To identify thrombotic risk factors in a cohort of APS patients. We conducted a retrospective review of APS patients who received care at a Hematology clinic of a university medical center from 2004 to 2017. Demographics, clinical features, antithrombotic therapy and thrombotic outcomes were collected. Time to event analysis identified clinical risk factors for thrombosis. The time varying effects of antithrombotic treatments on thrombosis outcome were analyzed. We identified 84 subjects with APS with a median age at diagnosis of 40.7 years [interquartile range [IQR] 33.5-57.6]. The majority were female (n = 63, 75%) and White (n = 45, 54%). Twenty-eight (33%) patients had concomitant autoimmune disease (AID) and of these, 15 (54%) had systemic lupus erythematosus. A thrombotic event occurred in 15 (18%) patients during a median follow-up of 48 months. A significantly higher rate of thrombotic events was observed in APS patients with AID compared to those without AID (hazard ratio (HR) 4.93, 95% CI 1.7-14.3, p = 0.04), and in black patients compared to whites (HR 5.94, 95% CI 1.1-32.1, p = 0.039). Patients on therapeutic anticoagulation regardless of type (warfarin, low molecular weight heparin or direct oral anticoagulants) were significantly less likely to have a recurrent thrombotic event compared to those on prophylactic anticoagulation (HR 0.11, 95% confidence interval [CI] 0.031-0.395, p = 0.001). However the numbers are too small to draw conclusions. Our study suggests that APS patients with concomitant AID and of Black race are at increased risk of recurrent thrombotic events.
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Síndrome Antifosfolípido/complicaciones , Factores de Riesgo , Trombosis/etiología , Adulto , Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/tratamiento farmacológico , Enfermedades Autoinmunes/complicaciones , Población Negra , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medicina de Precisión/métodos , Recurrencia , Estudios Retrospectivos , Trombosis/etnologíaRESUMEN
Background: Bone metastases are common in hepatocellular carcinoma (HCC), but their incidence, morbidity, and mortality are not well defined. Methods: The Memorial Sloan Kettering Cancer Center database was queried for all patients with HCC and metastases seen from 2002 to 2014. The prevalence of bone metastasis was determined and cumulative incidence function was used to estimate the probability of developing a bone metastasis. Regression models were created to identify risk factors for osseous metastasis. The frequency of skeletal-related events (SREs), defined as pathologic fracture, spinal cord compression, need for radiation therapy to bone, and/or surgical resection of bone, was determined and cumulative incidence function was used to estimate the probability of SRE development. Regression models were created to identify SRE risk factors. Correlation of clinicopathologic parameters, including bone metastases and SREs, with overall survival was analyzed using Kaplan-Meier methodology. Results: A total of 459 patients with HCC and extrahepatic metastases were identified; 151 patients (32.9%) had or developed bone metastases: 128 (27.9%) as a primary site and 23 (4.6%) as a secondary site of extrahepatic disease. Among the 331 patients without bone metastasis at presentation, the yearly incidence of bone metastasis was 6.4% (95% CI, 3.6%-9.2%). Hepatitis B virus (HBV) infection increased the chance of developing a bone metastasis (P=.02). The cumulative incidence of SREs was 50% at 6 months. Univariate analysis showed that patients with HBV-related HCC had a significantly higher incidence of SREs (P=.02). Sorafenib and bisphosphonates each protected against SREs. The presence of SREs was independently associated with a worse overall survival (hazard ratio, 2.13; 95% CI, 1.52-2.97; P<.01) in the multivariable model. Conclusions: Patients with AJCC stage IV HCC and bone metastases that are clinically evident on routine radiography or on clinical examination at presentation are apt to develop frequent, morbid, and mortal SREs, whereas those without evident bone metastasis at presentation are unlikely to develop these complications.
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Neoplasias Óseas/epidemiología , Neoplasias Óseas/secundario , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Anciano , Carcinoma Hepatocelular/etiología , Femenino , Humanos , Incidencia , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Morbilidad , Mortalidad , PronósticoAsunto(s)
Proteínas de Unión al ADN/genética , Proteína 7 que Contiene Repeticiones F-Box-WD/genética , Leucemia Linfocítica Crónica de Células B/mortalidad , Complejo Mediador/genética , Proteínas de Neoplasias/genética , Proteínas de Unión al ARN/genética , Receptor Notch1/genética , Transducción de Señal/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cromosomas Humanos Par 12 , Proteínas de Unión al ADN/fisiología , Proteína 7 que Contiene Repeticiones F-Box-WD/fisiología , Estudios de Seguimiento , Humanos , Inmunoterapia , Estimación de Kaplan-Meier , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/genética , Complejo Mediador/fisiología , Proteínas de Neoplasias/fisiología , Pronóstico , Supervivencia sin Progresión , Proteínas de Unión al ARN/fisiología , Receptor Notch1/fisiología , Tiempo de Tratamiento , Resultado del Tratamiento , Trisomía , Espera VigilanteRESUMEN
ABSTRACT: Cytoreductive therapy is not routinely recommended for younger patients with polycythemia vera (PV) due to concern that treatment toxicity may outweigh therapeutic benefits. However, no systematic data support this approach. To support objective risk/benefit assessment of cytoreductive drugs in patients with PV aged <60 years (PV<60), this systematic review and meta-analysis was conducted to evaluate toxicity and disease-related complications in PV<60 treated with interferon alfa (rIFN-α) or hydroxyurea (HU). A search of PubMed, Scopus, Web of Science and Embase identified 693 unique studies with relevant keywords, of which 14 met inclusion criteria and were selected for analysis. The weighted average age of patients treated with rIFN-α was 48 years (n = 744 patients; 12 studies) and for HU was 56 years (n = 1397; 8 studies). The weighted average duration of treatment for either drug was 4.5 years. Using a Bayesian hierarchical model, the pooled annual rate of discontinuation due to toxicity was 5.2% for patients receiving rIFN-α (n = 587; 95% confidence interval [CI], 2.2-8.2) and 3.6% for HU (n = 1097; CI, 1-6.2). The average complete hematologic response for rIFN-α and HU was 62% and 52%, respectively. Patients experienced thrombotic events at a pooled annual rate of 0.79% and 1.26%; secondary myelofibrosis at 1.06% and 1.62%; acute myeloid leukemia at 0.14% and 0.26%; and death at 0.87% and 2.65%, respectively. No treatment-related deaths were reported. With acceptable rates of nonfatal toxicity, cytoreductive treatment, particularly with disease-modifying rIFN-α, may benefit PV<60. Future randomized trials prioritizing inclusion of PV<60 are needed to establish a long-term benefit of early cytoreductive treatment in these patients.
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Policitemia Vera , Humanos , Policitemia Vera/tratamiento farmacológico , Policitemia Vera/complicaciones , Resultado del Tratamiento , Interferón-alfa/uso terapéutico , Interferón-alfa/efectos adversos , Hidroxiurea/uso terapéutico , Hidroxiurea/efectos adversos , Adulto , Persona de Mediana Edad , Procedimientos Quirúrgicos de Citorreducción , Factores de EdadRESUMEN
INTRODUCTION: Significant advances have been made in the diagnosis and management of patients with polycythemia vera (PV) over the past two decades, but a few important issues remain, either overlooked or controversial. AREAS COVERED: We discuss making an accurate diagnosis of PV with careful interpretation of hematocrit values, red cell count, and red cell mass when available, and bone marrow histomorphology to distinguish PV from other JAK2V617F myeloproliferative neoplasms (MPNs). We cover aspects of initial PV treatment with phlebotomy (PHL), its drawbacks in the long term, and alternative strategies. We comprehensively discuss cytoreductive therapy using interferon-alpha or hydroxyurea, with emphasis on patient selection, treatment goals, clinical endpoints, biomarkers and, most importantly, event-free and overall survival. EXPERT OPINION: A bone marrow biopsy in PV is essential for diagnosis and baseline histomorphology. Both hematocrit and red cell counts should be controlled with both phlebotomy (PHL) and cytoreductive agents. PHL alone is often inadequate in the long term, and cytoreduction is needed for most. Interferon is our preferred first-line agent due to improved survival outcomes. Short-term biomarkers predictive of long-term outcomes are needed to guide optimal therapy and development of new treatments.
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Trastornos Mieloproliferativos , Policitemia Vera , Humanos , Policitemia Vera/terapia , Policitemia Vera/tratamiento farmacológico , Hidroxiurea/uso terapéutico , Trastornos Mieloproliferativos/diagnóstico , Janus Quinasa 2/genética , Médula Ósea/patología , Interferón-alfa/uso terapéuticoRESUMEN
Background: Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) typically incur high rates of infections and both drugs and comorbidities may modulate infection risk. Objectives: The present study aims to assess the effect of immunosuppressive agents on clinical outcomes of MPN patients affected by the coronavirus disease 2019 (COVID-19). Design: This is an observational study. Methods: We specifically searched and analyzed MPN patients collected by EPICOVIDEHA online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020. Results: Overall, 398 patients with MPN were observed for a median of 76 days [interquartile range (IQR): 19-197] after detection of SARS-CoV2 infection. Median age was 69 years (IQR: 58-77) and 183 individuals (46%) had myelofibrosis (MF). Overall, 121 patients (30%) of the whole cohort received immunosuppressive therapies including steroids, immunomodulatory drugs, or JAK inhibitors. Hospitalization and consecutive admission to intensive care unit was required in 216 (54%) and 53 patients (13%), respectively. Risk factors for hospital admission were identified by multivariable logistic regression and include exposure to immunosuppressive therapies [odds ratio (OR): 2.186; 95% confidence interval (CI): 1.357-3.519], age ⩾70 years, and comorbidities. The fatality rate was 22% overall and the risk of death was independently increased by age ⩾70 years [hazard ratio (HR): 2.191; 95% CI: 1.363-3.521], previous comorbidities, and exposure to immunosuppressive therapies before the infection (HR: 2.143; 95% CI: 1.363-3.521). Conclusion: COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals. Plain language summary: EPICOVIDEHA registry reports inferior outcomes of COVID-19 in patients with Philadelphia-negative chronic myeloproliferative neoplasms receiving immunosuppressive therapies. Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) incur high rates of infections during the course of their disease.The present study was aimed at assessing which patient characteristics predicted a worse outcome of SARS-COV-2 infection in individuals with MPN.To pursue this objective, the researchers analyzed the data collected by EPICOVIDEHA, an international online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020.The database provided clinical data of 398 patients with MPN incurring COVID-19:Patients were mostly elderly (median age was 69 years);Forty-six percent of them were affected by myelofibrosis, which is the most severe MPN;Moreover, 32% were receiving immunosuppressive therapies (JAK inhibitors, such as ruxolitinib, steroids, or immunomodulatory IMID drugs, such as thalidomide) before COVID-19.Hospitalization was required in 54% of the patients, and the risk of being hospitalized for severe COVID-19 was independently predicted byOlder age;Comorbidities;Exposure to immunosuppressive therapies.Overall, 22% of MPN patients deceased soon after COVID-19 and the risk of death was independently increased over twofold byOlder age;Comorbidities;Exposure to immunosuppressive therapies before the infection.In conclusion, COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents, including JAK inhibitors, or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals.
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OBJECTIVES: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. METHODS: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. RESULTS: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. CONCLUSION: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.
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COVID-19 , Neoplasias Hematológicas , Linfopenia , Anciano , Humanos , Masculino , Anciano de 80 o más Años , Femenino , Vacunación , Inmunización , Neoplasias Hematológicas/complicacionesRESUMEN
Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs.
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Interferon-alpha (rIFNα) is the only disease-modifying treatment for polycythemia vera (PV), but whether or not it prolongs survival is unknown. This large single center retrospective study of 470 PV patients compares the myelofibrosis-free survival (MFS) and overall survival (OS) with rIFNα to two other primary treatments, hydroxyurea (HU) and phlebotomy-only (PHL-O). The median age at diagnosis was 54 years (range 20-94) and the median follow-up was 10 years (range 0-45). Two hundred and twenty-nine patients were women (49%) and 208 were high-risk (44%). The primary treatment was rIFNα in 93 (20%), HU in 189 (40%), PHL-O in 133 (28%) and other cytoreductive drugs in 55 (12%). The treatment groups differed by ELN risk score (p < 0.001). In low-risk patients, 20-year MFS for rIFNα, HU, and PHL-O was 84%, 65% and 55% respectively (p < 0.001) and 20-year OS was 100%, 85% and 80% respectively (p = 0.44). In high-risk patients, 20-year MFS for rIFNα, HU, and PHL-O was 89%, 41% and 36% respectively (p = 0.19) and 20-year OS was 66%, 40%, 14% respectively (p = 0.016). In multivariable analysis, longer time on rIFNα was associated with a lower risk of myelofibrosis (HR: 0.91, p < 0.001) and lower mortality (HR: 0.94, p = 0.012). In conclusion, this study supports treatment of PV with rIFNα to prevent myelofibrosis and potentially prolong survival.
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Antivirales/uso terapéutico , Interferón-alfa/uso terapéutico , Policitemia Vera/mortalidad , Mielofibrosis Primaria/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Policitemia Vera/tratamiento farmacológico , Policitemia Vera/patología , Mielofibrosis Primaria/prevención & control , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
Sideroblastic anemia (SA) consists of a group of inherited and acquired anemias of ineffective erythropoiesis characterized by the accumulation of ring sideroblasts in the bone marrow due to disrupted heme biosynthesis. Congenital sideroblastic anemia (CSA) is rare and has three modes of inheritance: X-linked (XLSA), autosomal recessive (ARCSA), and maternal. Acquired SA is more common and can be a result of myelodysplastic syndromes (MDS) or other, generally reversible causes. The diagnostic approach to SA includes a work-up for reversible causes and genetic testing for CSA based on clinical suspicion, family history and genetic pedigree. The treatment of SA depends on the underlying etiology but remains primarily supportive with vitamin B6 supplementation for select cases of XLSA, thiamine for thiamine-responsive megaloblastic anemia subtype, red blood cell transfusions for symptomatic patients and iron chelation therapy for iron overload. The management of anemia in MDS subtypes with ring sideroblasts remains unique and includes the recently approved erythroid maturation agent, Luspatercept. Although there is currently no curative therapy for CSA, anecdotal reports of hematopoietic stem cell transplant demonstrate remissions in selective, non-syndromic cases. This review summarizes the genetics, pathophysiology, diagnosis and treatment of SA for general practitioners and clinical hematologists.
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Progresión de la Enfermedad , Trombosis , Humanos , Trombosis/etiología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Pronóstico , AdultoAsunto(s)
Esperanza de Vida , Policitemia Vera/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Policitemia Vera/patología , Policitemia Vera/terapia , Pronóstico , Tasa de Supervivencia , Adulto JovenRESUMEN
Hepatocellular carcinoma (HCC) is often diagnosed on the basis of high quality imaging without a biopsy in the cirrhotic liver. This is a case of a 64-year-old Caucasian man with no history of liver disease or cirrhosis that presented with fatigue, weight loss, and abdominal distension and was found to have a large, isolated liver mass with arterial enhancement and portal venous washout on triple-phase computed tomography (CT) suspicious for HCC. The patient was initially referred for a surgical evaluation. Meanwhile, he developed fevers, pancytopenia, and worsening back pain, and a subsequent spinal MRI revealed a heterogeneous bone marrow signal suspicious for metastatic disease. A bone marrow biopsy that followed was diffusely necrotic. A core biopsy of the patient's liver mass was then performed and was diagnostic of acute monocytic-monoblastic leukemia. Findings from peripheral flow cytometry and a repeat bone marrow biopsy were also consistent with this diagnosis, and induction chemotherapy with cytarabine and idarubicin was initiated. This case describes a rare presentation of myeloid sarcoma (MS) as an isolated, hypervascular liver mass that mimics HCC in its radiographic appearance. Due to the broad differential for a liver mass, a confirmatory biopsy should routinely be considered prior to surgical intervention.