RESUMO
We describe the case of a patient with extreme thrombocytosis whose evolution was rapidly fatal. No cause of secondary thrombocytosis was found. There was no sign of myelofibrosis but the megakaryocytes were small and dysplastic. The patient presented a calreticulin (CALR) variant in exon 3 (C105S), as well as concomitant mutations of ASXL1, U2AF1, and EZH2. This variant of CALR has never been described before, and after sorting, all identified mutations were found in myeloid cells but not in lymphoid cells. Therefore, the diagnosis of a frontier case of myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) was made. A treatment with hydroxycarbamide was started because of a high risk of thrombosis. Upon worsening of the hematological status two new mutations appeared, SETBP1 and ETV6, and the CALR mutation was still detectable, as well as the three other mutations found in the chronic stage. Our results show that this variant could contribute to MDS/MPN pathogenesis in that patient.
Assuntos
Doenças Mieloproliferativas-Mielodisplásicas , Transtornos Mieloproliferativos , Mielofibrose Primária , Trombocitose , Humanos , Calreticulina/genética , Calreticulina/metabolismo , Trombocitose/diagnóstico , Mutação , Mielofibrose Primária/genética , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Éxons , Transtornos Mieloproliferativos/genética , Janus Quinase 2/genéticaRESUMO
Myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is a rare hematologic malignancy belonging to the category of myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes. While certain clinical features, including anemia and thrombocytosis, are common to both the MDS and MPN disease components, the biologic consequences of the spliceosome mutation SF3B1 results in notable clinical exceptions. Importantly, both overall and leukemia free survival are shorter for MDS/MPN-RS-T when compared to essential thrombocythemia (ET). In the case of MDS/MPN-RS-T, thrombotic risk is not associated with the presence of JAK2V617F, nor history of prior thrombosis, but is associated with the presence of the mutated spliceosome gene SF3B1. In this review, we highlight the biology, pathology, risk stratification, and treatment approach to MDS/MPN-RS-T. In particular, we focus on clinical management concepts, which are largely borrowed from MDS and MPN, including the use of cytoreduction, bone marrow stimulating agents, and the role of allogeneic stem cell transplantation. We end by highlighting unmet needs and future research priorities in MDS/MPN-RS-T.
Assuntos
Anemia Sideroblástica , Neoplasias Hematológicas , Doenças Mieloproliferativas-Mielodisplásicas , Transtornos Mieloproliferativos , Trombocitose , Anemia Sideroblástica/genética , Anemia Sideroblástica/patologia , Anemia Sideroblástica/terapia , Neoplasias Hematológicas/complicações , Humanos , Mutação , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Doenças Mieloproliferativas-Mielodisplásicas/genética , Doenças Mieloproliferativas-Mielodisplásicas/terapia , Transtornos Mieloproliferativos/complicações , Fatores de Processamento de RNA/genética , Síndrome , Trombocitose/genética , Trombocitose/terapiaAssuntos
Janus Quinase 2/genética , Doenças Mieloproliferativas-Mielodisplásicas/patologia , Fosfoproteínas/genética , Fatores de Processamento de RNA/genética , Trombocitose/patologia , Idoso , Feminino , Humanos , Mutação , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Doenças Mieloproliferativas-Mielodisplásicas/genética , Trombocitose/complicações , Trombocitose/genéticaRESUMO
OBJECTIVES: GCA is a large vessel vasculitis for which triggering factors remain unknown. Clonal haematopoiesis (CH) was associated with atherosclerosis through the induction of inflammation in myeloid cells, and data suggest that CH expansion and inflammation may support each other to induce a pro-inflammatory loop. Our objective was to describe the impact of JAK2p.V617F-mutated myeloproliferative neoplasms (MPNs) on GCA and to screen MPN-free patients for CH mutations. METHODS: We performed a retrospective case-control study comparing the characteristics of 21 GCA patients with MPN and 42 age- and gender-matched GCA patients without MPN. Also, 18 GCA patients were screened for CH through next-generation sequencing (NGS). RESULTS: The most frequent associated MPN was essential thrombocythaemia (ET; n = 11). Compared with controls, GCA patients with MPN had less-frequent cephalic symptoms (71.4 vs 97.6%; P = 0.004) and higher platelet counts at baseline [485 × 109/l (interquartile range 346-586) vs 346 (296-418); P = 0.02]. There was no difference between groups for other clinical features. Overall survival was significantly shorter in patients with MPN compared with controls [hazard ratio 8.2 (95% CI 1.2, 56.6); P = 0.03]. Finally, screening for CH using NGS in 15 GCA patients without MPN revealed CH in 33%. CONCLUSION: GCA patients with MPN display higher platelet counts and shorter overall survival than controls. This association is not fortuitous, given the possible pathophysiological relationship between the two diseases. CH was found in one-third of GCA patients, which may be higher than the expected prevalence for a similar age, and should be confirmed in a larger cohort.
Assuntos
Hematopoiese Clonal , Arterite de Células Gigantes/etiologia , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Hematopoiese Clonal/genética , Feminino , Arterite de Células Gigantes/genética , Arterite de Células Gigantes/mortalidade , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Janus Quinase 2/genética , Masculino , Doenças Mieloproliferativas-Mielodisplásicas/genética , Doenças Mieloproliferativas-Mielodisplásicas/mortalidade , Contagem de Plaquetas , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is characterized by anemia, ring sideroblast erythroid precursors, and persistent thrombocytosis. Case reports suggest lenalidomide may be effective in treating MDS/MPN-RS-T. We evaluated a large series of patients with MDS/MPN-RS-T to compare hematological improvement (HI) response rates among different drug therapies including lenalidomide. We identified 167 patients with MDS/MPN-RS-T. Among the patients tested, 84% had SF3B1 mutations and 43% had JAK2 V617F mutations. The median OS for the cohort was 81 months. Overall, 76 patients (46%) received erythropoiesis-stimulating agents (ESAs), 47 patients (28%) received lenalidomide, and 45 patients (27%) received hypomethylating agents (HMAs). The HI rates were 58%, 53%, and 24%, respectively. The median duration of treatment was 11 months for lenalidomide compared to 6 months for HMAs. Rates of HI improvement were higher in patients with MDS/MPN-RS-T treated with ESAs or lenalidomide, in comparison to those treated with HMAs.
Assuntos
Anemia Sideroblástica , Doenças Mieloproliferativas-Mielodisplásicas , Neoplasias , Trombocitose , Anemia Sideroblástica/diagnóstico , Anemia Sideroblástica/tratamento farmacológico , Anemia Sideroblástica/etiologia , Humanos , Mutação , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Doenças Mieloproliferativas-Mielodisplásicas/diagnóstico , Doenças Mieloproliferativas-Mielodisplásicas/tratamento farmacológico , Trombocitose/tratamento farmacológico , Trombocitose/genética , Resultado do TratamentoRESUMO
Myeloproliferative neoplasms (MPN) are a heterogeneous group of hematological disorders presenting with an increased proliferation in one or several hematological cell lines. Renal manifestations of MPN have not been fully characterized so far. To morphologically assess the potential renal involvement in MPN patients, we analyzed histomorphological findings of a post-mortem cohort (n = 57) with a disease history of Philadelphia-negative MPN including polycythaemia vera, primary myelofibrosis, essential thrombocythemia, or chronic myelomonocytic leukemia (CMML). Seven (12.2%) patients presented with a pattern of diffuse glomerulosclerosis not attributable to diabetic or hypertensive nephropathy. Weak C4d staining suggestive for chronic thrombotic microangiopathy (TMA) was observed in 4/7 cases. Glomerulonephritis was excluded by light microscopy and immunohistochemistry. Patients with a pattern of diffuse glomerulosclerosis did not differ from the rest of the cohort regarding MPN subtype, disease duration, age, or sex. No significant proteinuria had been observed before death. Further findings attributed to MPNs were extramedullary hematopoiesis (n = 5; 8.8%) and tumor involvement in advanced disease (n = 4; 7.0%). Other common findings included arteriolosclerosis (n = 18; 31.6%) and signs of shock (n = 8; 14.0%). To our knowledge, this study is so far the largest investigating renal findings in MPN patients. There may be a causal relationship between idiopathic diffuse glomerular sclerosis and MPN, although its clinical significance and pathophysiology remain uncertain with TMA probably being relevant in a subgroup of cases. Our findings demonstrate the spectrum of renal findings in MPN from early to terminal disease of which hematologists should be aware of in daily clinical practice.
Assuntos
Nefropatias/etiologia , Rim/patologia , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade , Doenças Mieloproliferativas-Mielodisplásicas/diagnóstico , Doenças Mieloproliferativas-Mielodisplásicas/mortalidade , Doenças Mieloproliferativas-Mielodisplásicas/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
Secondary thrombocytosis is a frequent secondary finding in childhood infection and inflammation. Primary hereditary thrombocytosis may be caused by germline mutations within the genes encoding key regulators of thrombopoiesis, i.e., thrombopoietin (THPO) and its receptor c-MPL (MPL) or the receptor's effector kinase Januskinase2 (JAK2). Furthermore, somatic mutations in JAK2, MPL, and in the gene-encoding calreticulin (CALR) have been described to act as driver mutations within the so-called Philadelphia-negative myeloproliferative neoplasms (MPNs), namely essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). Increasing knowledge on the molecular mechanisms and on the clinical complications of these diseases is reflected by the WHO diagnostic criteria and European LeukemiaNet (ELN) recommendations on the management of adult MPN. However, data on childhood thrombocytosis are rare, and no consensus guidelines for pediatric thrombocytosis exist. Current literature has highlighted differences in the epidemiology and molecular pathogenesis of childhood thrombocytosis as compared to adults. Furthermore, age-dependent complications and pharmacological specificities suggest that recommendations tailored to the pediatric population are necessary in clinical practice. Here we summarize literature on classification, diagnostics, and clinical management of childhood thrombocytosis.
Assuntos
Trombocitose , Adolescente , Adulto , Idade de Início , Algoritmos , Anticoagulantes/uso terapêutico , Calreticulina/genética , Criança , Gerenciamento Clínico , Feminino , Mutação em Linhagem Germinativa , Humanos , Hidroxiureia/uso terapêutico , Interferon-alfa/uso terapêutico , Janus Quinase 2/genética , Masculino , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Contagem de Plaquetas , Quinazolinas/uso terapêutico , Receptores de Trombopoetina/genética , Índice de Gravidade de Doença , Trombocitemia Essencial/classificação , Trombocitemia Essencial/genética , Trombocitose/classificação , Trombocitose/diagnóstico , Trombocitose/etiologia , Trombocitose/terapia , Trombofilia/tratamento farmacológico , Trombofilia/etiologiaAssuntos
Eritroblastos/patologia , Janus Quinase 2/genética , Leucemia Mieloide Aguda/patologia , Mutação , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Mielofibrose Primária/patologia , Trombocitose/complicações , Calreticulina/genética , Humanos , Leucemia Mieloide Aguda/etiologia , Masculino , Pessoa de Meia-Idade , Doenças Mieloproliferativas-Mielodisplásicas/genética , Fosfoproteínas/genética , Mielofibrose Primária/etiologia , Prognóstico , Fatores de Processamento de RNA/genética , Trombocitose/genéticaRESUMO
AIMS: Renal changes in patients with myeloproliferative neoplasms (MPNs) or myelodysplastic syndrome (MDS)/MPNs have been addressed by few, respectively no, reports. The aim of this study was to focus on a systematic evaluation of renal biopsies in patients with MPNs or MDS/MPNs. METHODS AND RESULTS: The cohort comprised 29 patients (23 men) aged 67 ± 11 years (mean ± standard deviation), diagnosed with chronic myeloid leukaemia (n = 5), polycythaemia vera (n = 9), primary myelofibrosis (n = 5), essential thrombocythaemia (n = 2), or chronic myelomonocytic leukaemia (n = 4), as well as MPNs or MDS/MPNs not otherwise specified (n = 4). Patients manifested with proteinuria (93%), partially in the nephrotic range (46%), haematuria (72%), and impaired kidney function (93%). The most prominent histological findings included double-contoured glomerular basement membranes (71%), acute endothelial damage (68%), intracapillary platelet aggregation (62%), mesangiolysis (21%), thrombotic microangiopathy (24%), segmental glomerulosclerosis (66%), mesangial hypercellularity and sclerosis, extramedullary haematopoiesis (17%), and also IgA nephropathy (21%) and glomerulonephritis (GN) with features of infection-related GN (21%). MPN and MDS/MPN patients showed significantly more chronic changes than age-matched and sex-matched controls, including global and segmental glomerulosclerosis, mesangial sclerosis, and hypercellularity, whereas the extent of arteriosclerosis was comparable. CONCLUSIONS: MPN and MDS/MPN patients show glomerular scarring that exceeds age-related phenomena. Ongoing endothelial damage, growth factors released by platelets and deposition of immune complexes are probably the causative mechanisms. Early recognition of renal failure heralded by proteinuria and haematuria, and consequent control of risk factors for kidney failure, should be recommended for MPN and MDS/MPN patients.
Assuntos
Nefropatias/etiologia , Doenças Mieloproliferativas-Mielodisplásicas , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Glomerulonefrite/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Transtornos Mieloproliferativos/complicações , Neoplasias/complicações , Fatores de Risco , Microangiopatias Trombóticas/etiologiaAssuntos
Vasos Sanguíneos/metabolismo , Sobrecarga de Ferro/patologia , Ferro/metabolismo , Metais Pesados/metabolismo , Idoso de 80 Anos ou mais , Anemia Sideroblástica/etiologia , Anemia Sideroblástica/patologia , Anemia Sideroblástica/terapia , Arteriosclerose/etiologia , Arteriosclerose/metabolismo , Arteriosclerose/patologia , Biópsia , Transfusão de Sangue , Vasos Sanguíneos/patologia , Medula Óssea/metabolismo , Medula Óssea/patologia , Deferasirox/uso terapêutico , Feminino , Humanos , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Doenças Mieloproliferativas-Mielodisplásicas/patologia , Doenças Mieloproliferativas-Mielodisplásicas/terapia , Trombocitose/etiologia , Trombocitose/patologia , Trombocitose/terapia , Reação Transfusional/complicações , Reação Transfusional/tratamento farmacológico , Reação Transfusional/patologia , Falha de TratamentoRESUMO
Objective: Myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is a new disease entity in the 2016 WHO classification, characterized by anemia, thrombocytosis and bone marrow ring sideroblasts. We herein reported a case of MDS/MPN-RS-T and discuss its clinical characteristics. Methods: A 69-year-old woman presented to our hospital with recurrent dizziness and fatigue. Hematologic investigations, bone marrow analysis and genomic DNA sequencing studies were performed. Results: Peripheral blood testing showed normocytes anemia and thrombocytosis, and bone marrow analysis revealed hypercellular with clusters of megakaryocytes and 95% ring sideroblasts (RS). She had a normal karyotype and was found to have SF3B1 mutations. Decitabine therapy produced a clinical response and disease remission in this patient. Conclusions: Our report provides a definite conceptual framework for a better understanding of the characteristics of MDS/MPN-RS-T.
Assuntos
Medula Óssea/patologia , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Trombocitose/complicações , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Medula Óssea/efeitos dos fármacos , Decitabina/uso terapêutico , Feminino , Humanos , Doenças Mieloproliferativas-Mielodisplásicas/tratamento farmacológico , Doenças Mieloproliferativas-Mielodisplásicas/genética , Doenças Mieloproliferativas-Mielodisplásicas/patologia , Trombocitose/tratamento farmacológico , Trombocitose/genética , Trombocitose/patologiaRESUMO
INTRODUCTION: Myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasms (MDS/MPN) can be associated with giant cell arteritis (GCA). In this nationwide study by the "French Network of dysimmune disorders associated with hemopathies" (MINHEMON) the objective was to evaluate characteristics, treatment and outcome of GCA MDS-MDS/MPN. PATIENTS AND METHODS: Retrospective analysis of patients that presented a MDS or MDS/MPN associated with GCA. Treatment efficiency, relapse-free and overall survival of GCA MDS-MDS/MPN were compared to GCA alone. RESULTS: Twenty-one patients with GCA MDS-MDS/MPN were included with median age 76 [42-92], M/F ratio 2.5, 8 MDS with multilineage dysplasia (38%), 4 chronic myelomonocytic leukemia (19%), at low or intermediate risk according to IPPS and IPSS-R. The prevalence of headaches, jaw claudication and anterior ischemic optic neuropathy was significantly lower in patients with GCA MDS-MDS/MPN compared to idiopathic GCA (14.3%, 0% and 0% versus 30%, 25%, and 25%, respectively; p < .05). Other clinical and histology findings were similar. All GCA patients received steroid therapy as first-line treatment. Complete or partial response was observed in 14 GCA MDS-MDS/MPN patients (66.7%), of whom 6 (28.6%) received combined immunosuppressive therapies (versus 10% of idiopathic GCA; p = .07). Relapse incidence was similar in the two groups. Steroid dependence was more frequent among GCA MDS-MDS/MPN patients (12 (57%) versus 18 (22.5%); p < .05). Relapse-free and steroid-free survivals were significantly decreased in GCA MDS-MDS/MPN patients (log rank 0.002 and 0.049 respectively), but not overall survival. CONCLUSION: Characteristics of GCA MDS-MDS/MPN seem different than idiopathic GCA, with a distinct clinical phenotype and poorer outcome with a higher risk of steroid dependence and relapse.
Assuntos
Arterite de Células Gigantes/complicações , Síndromes Mielodisplásicas/complicações , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/patologia , Doenças Mieloproliferativas-Mielodisplásicas/tratamento farmacológico , Doenças Mieloproliferativas-Mielodisplásicas/patologia , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A 59-year-old white man with known myeloproliferative neoplasm (MPN) and myelodysplastic syndrome (MDS) presented with worsening leucocytosis and thrombocytosis in the setting of a presumed infection. The patient had been diagnosed 2 years earlier with an MPN/MDS overlap syndrome, based on characteristic mutations in JAK2, IDH1 and SRSF2. During his current evaluation, he was noted to have new microcytosis, with a mean corpuscular volume of ~70 fL down from his baseline of ~90 fL. His laboratory workup showed normal iron studies, normal haemoglobin electrophoresis, and no evidence of haemoglobin H or mutations in his ATRX coding region. Without any identifiable cause of his new microcytosis, he was given a presumptive diagnosis of acquired thalassemia in the setting of his unusual MPN/MDS overlap syndrome.
Assuntos
Esclerose Lateral Amiotrófica , Leucocitose/diagnóstico , Doenças Mieloproliferativas-Mielodisplásicas/diagnóstico , Policitemia Vera/diagnóstico , Contagem de Células Sanguíneas , Evolução Fatal , Humanos , Leucocitose/sangue , Leucocitose/complicações , Masculino , Pessoa de Meia-Idade , Doenças Mieloproliferativas-Mielodisplásicas/sangue , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Policitemia Vera/sangue , Policitemia Vera/complicaçõesRESUMO
Myelodysplastic/myeloproliferative neoplasm (MDS/MPN) with ring sideroblasts and thrombocytosis (MDS/MPN with RS-T), which exhibits both an increased number of marrow ring sideroblasts and thrombocytosis, is a rare disorder classified as one of the newly established forms of MDS/MPN in the WHO 2016 classification. A 77-year-old female with marked thrombocytosis of 1,024×109/L was tentatively diagnosed with essential thrombocythemia in 2011, and the thrombocytosis was controlled using hydroxycarbamide and low-dose busulfan. In 2016, the leukocyte count increased to a peak value of 68.8×109/L (86.6% mature neutrophils) during platelet-reduction therapy. Bone marrow aspirate exhibited hypercellularity with ring sideroblasts comprising 41.5% erythroblasts without excess myeloblasts. Cytogenetic examination demonstrated the JAK2 V617F mutation and chromosomal abnormality of 46,XX,del(20)(q1?). Furthermore, dysplastic features of erythroid and granuloid precursors, as well as many large atypical megakaryocytes, were observed. Further genetic examinations revealed the SF3B1 K700E mutation, but not amplification of the JAK2 gene or pathogenic mutations in the 13 other genes examined. A diagnosis of MDS/MPN with RS-T was established and hyperleukocytosis was controlled using a higher dose of hydroxycarbamide. Although the patient maintained a stable disease state, she became RBC transfusion-dependent. Hyperleukocytosis, regardless of chemotherapy, is rare and may be novel in this disorder.
Assuntos
Anemia Sideroblástica , Leucocitose/etiologia , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Trombocitose , Idoso , Transfusão de Eritrócitos , Feminino , Humanos , Leucocitose/genética , MutaçãoRESUMO
INTRODUCTION: Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is a rare disease in the 2016 revised World Health Organization (WHO) classification. Diagnostic criteria include the following: persistent thrombocytosis (>450 × 109 /L) with clustering of atypical megakaryocytes, refractory anemia, dyserythropoiesis with ring sideroblasts, and the presence of the spliceosome factor 3b subunit (SF3B1) mutation. It is unclear if anemia should be a required criterion for this diagnosis as cases which show all other features of MDS/MPN-RS-T but without anemia exist. METHODS: We searched for borderline cases of MDS/MPN-RS-T in which refractory anemia was absent at diagnosis in two major academic institutes. RESULTS: Three cases without anemia were identified. These cases all showed other classic morphologic and clinical features of MDS/MPN-RS-T, including thrombocytosis, atypical megakaryocytes with clustering, and characteristic SF3B1 and JAK2 V617F mutations. CONCLUSION: Given these findings, the requirement of refractory anemia as a diagnostic criterion for MDS/MPN-RS-T should be re-evaluated. Removal of refractory anemia as a diagnostic criterion would incorporate current borderline cases and extend the spectrum of this disorder.
Assuntos
Anemia Sideroblástica/sangue , Doenças Mieloproliferativas-Mielodisplásicas/sangue , Doenças Mieloproliferativas-Mielodisplásicas/diagnóstico , Trombocitose/sangue , Idoso de 80 Anos ou mais , Anemia Sideroblástica/etiologia , Biomarcadores , Biópsia , Medula Óssea/patologia , Células da Medula Óssea/patologia , Análise Citogenética , Feminino , Citometria de Fluxo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Mutação , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Doenças Mieloproliferativas-Mielodisplásicas/etiologia , Fosfoproteínas/genética , Fatores de Processamento de RNA/genética , Análise de Sequência de DNA , Trombocitose/etiologiaRESUMO
Patients with cancer are at high risk for tuberculosis (TB). This study combined the Israeli databases of cancer and TB and examined the development of TB among all newly diagnosed cancer cases from 1993 to 2013. Patients were classified into groups according to their different malignancies. Among 495,335 cancer patients, 335 developed TB following cancer diagnosis. The cumulative incidence of TB following cancer diagnosis was highest among MDS/MPN (148.8/100,000 patients) and lymphoma (154.1/100,000 patients) (p = .023). The HR of TB following cancer among hematologic patients was 2.51 (p < .001), relative to patients with in situ carcinomas/skin cancer and highest among MDS/MPN and lymphoma patients (2.74, p = .012 and 2.70, p < .001, respectively). Among lymphoma patients, a significant increased HR was found only among NHL patients (2.72, p < .001). The limitations include lack of information regarding risk factors for TB and of anti-cancer treatments. In conclusion, these data may encourage a heightened awareness for TB among patients with a background of lymphoma and MDS/MPN.
Assuntos
Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/epidemiologia , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Doenças Mieloproliferativas-Mielodisplásicas/epidemiologia , Tuberculose/epidemiologia , Tuberculose/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Doenças Mieloproliferativas-Mielodisplásicas/diagnóstico , Vigilância da População , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Análise de Sobrevida , Tuberculose/diagnóstico , Adulto JovemRESUMO
OBJECTIVE: We report cases of myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) with trisomy 8 associated with inflammatory and autoimmune diseases (IADs). METHOD: Data for 21 patients with trisomy 8-MDS/MPN and IADs were analyzed and compared to 103 patients with trisomy 8-MDS/MPN without IADs. RESULTS: The median age of MDS/MPN patients with IADs was 67 [59-80]. The IADs were Behçet's-like disease in 11 (52%) patients, inflammatory arthritis in 4 (19%) and Sjögren's syndrome, autoimmune hemolytic anemia, aseptic abscess, periarteritis nodosa, Sweet's syndrome and unclassified vasculitis in one patient each. Overall, 17/21 (81%) patients with IADs received treatment (88% with steroids), with complete and partial response in 7/17 (35%) and 8/17 (47%), respectively. The effect of MDS treatment on IADs could be assessed in seven patients receiving azacytidine: five achieved remission and two partial response. As compared with the 103 trisomy 8-MDS/MPN cases without IADs, those with IADs were more often non-European (P = 0.005) and had poor karyotype (P < 0.001). We found no difference in overall survival or acute myeloid leukemia progression between trisomy 8-associated MDS/MPN with and without IADs. CONCLUSION: The spectrum of IADs associated with trisomy 8-positive MDS/MPN is dominated by Behçet's-like disease. Steroid therapy is effective, but mostly sparing therapies are necessary. Azacytidine could be an effective alternative.
Assuntos
Inflamação/etiologia , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/genética , Trissomia/genética , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/etiologia , Estudos de Casos e Controles , Cromossomos Humanos Par 8/genética , Progressão da Doença , Feminino , Seguimentos , França , Humanos , Inflamação/diagnóstico , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/mortalidade , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Doenças Mieloproliferativas-Mielodisplásicas/diagnóstico , Doenças Mieloproliferativas-Mielodisplásicas/genética , Doenças Mieloproliferativas-Mielodisplásicas/mortalidade , PrognósticoRESUMO
We report the 11 cases of +8-MDS/MPN associated with Behcet's-like syndrome and compare them with Behcet's disease and Crohn's disease, pool with literature cases for analysis. Data for patients with +8-MDS/MPN and Behçet's-like syndrome were collected from MINHEMON. Eleven patients had Behcet's-like syndrome and +8-MDS/MPN (median age 75 years [IQR 65-87]; M/F ratio 0.8). MDS and Behcet's-like syndrome were diagnosed at the same time (7/11, 64%). By comparison with 63 patients with idiopathic Behcet's disease without associated MDS, those with Behcet's-like syndrome and +8-MDS/MPN were older (median 75 vs 48 years; p = .0003) and had less pseudofolliculitis (11% vs 62%; p = .0045) and ocular impairment (0% vs 52%; p = .0008), but more frequent gastrointestinal involvement (60% vs 13%; p = .0005). By comparison with Crohn's disease, 39 patients with Behcet's-like syndrome and +8-MDS/MPN were significantly older (median 72 [53-78] vs 36 [27-45] years; p = .0002) and more frequently had oral aphtosis (97% vs 5%, p < .0001), skin features (50% vs 10%, p = .0005) and arthralgia (63% vs 20%, p = .03). Median survival did not differ between patients with Behcet's-like syndrome and +8-MDS/MPN and those with +8-MDS/MPN (n = 103) (47 vs 34 months, p = .61). AML-free survival did not differ between patients with MDS/MPN with and without Behcet's-like syndrome (p = .29). MDS/MPN with trisomy 8 can be associated with particular phenotype of ulcerative digestive disease resembling Behcet's or Crohn's disease and should be considered a single disease.