Assuntos
Leucocitose/sangue , Monócitos/metabolismo , Síndromes Mielodisplásicas/sangue , Doenças Mieloproliferativas-Mielodisplásicas/sangue , Transtornos Mieloproliferativos/sangue , Neoplasias/sangue , Idoso , Diagnóstico Diferencial , Feminino , Citometria de Fluxo/métodos , Humanos , Leucemia Mielomonocítica Crônica/sangue , Leucemia Mielomonocítica Crônica/diagnóstico , Contagem de Leucócitos , Leucocitose/diagnóstico , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Doenças Mieloproliferativas-Mielodisplásicas/diagnóstico , Transtornos Mieloproliferativos/diagnóstico , Neoplasias/diagnóstico , Estudos Retrospectivos , Sensibilidade e EspecificidadeAssuntos
Tratamento Farmacológico da COVID-19 , Hidroxiureia/administração & dosagem , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Insuficiência Respiratória/tratamento farmacológico , SARS-CoV-2 , COVID-19/sangue , COVID-19/diagnóstico por imagem , Humanos , Leucemia Mielomonocítica Crônica/sangue , Leucemia Mielomonocítica Crônica/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/sangue , Insuficiência Respiratória/diagnóstico por imagemAssuntos
Hepatomegalia/etiologia , Hipoglicemia/etiologia , Leucemia Mielomonocítica Crônica/sangue , Leucemia Mielomonocítica Crônica/complicações , Esplenomegalia/etiologia , Adulto , Hepatomegalia/diagnóstico por imagem , Humanos , Hipoglicemia/sangue , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Leucócitos/citologia , Masculino , Esplenomegalia/diagnóstico por imagem , Tomógrafos ComputadorizadosAssuntos
Autoanticorpos/imunologia , Leucemia Mielomonocítica Crônica/imunologia , Síndromes Mielodisplásicas/imunologia , Autoanticorpos/sangue , Biomarcadores , Humanos , Leucemia Mielomonocítica Crônica/sangue , Leucemia Mielomonocítica Crônica/diagnóstico , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/diagnóstico , PrognósticoRESUMO
Chronic myelomonocytic leukemia (CMML) is a clinically heterogeneous neoplasm in which JAK2 inhibition has demonstrated reductions in inflammatory cytokines and promising clinical activity. We hypothesize that annotation of inflammatory cytokines may uncover mutation-independent cytokine subsets associated with novel CMML prognostic features. A Luminex cytokine profiling assay was utilized to profile cryopreserved peripheral blood plasma from 215 CMML cases from three academic centers, along with center-specific, age-matched plasma controls. Significant differences were observed between CMML patients and healthy controls in 23 out of 45 cytokines including increased cytokine levels in IL-8, IP-10, IL-1RA, TNF-α, IL-6, MCP-1/CCL2, hepatocyte growth factor (HGF), M-CSF, VEGF, IL-4, and IL-2RA. Cytokine associations were identified with clinical and genetic features, and Euclidian cluster analysis identified three distinct cluster groups associated with important clinical and genetic features in CMML. CMML patients with decreased IL-10 expression had a poor overall survival when compared to CMML patients with elevated expression of IL-10 (P = 0.017), even when adjusted for ASXL1 mutation and other prognostic features. Incorporating IL-10 with the Mayo Molecular Model statistically improved the prognostic ability of the model. These established cytokines, such as IL-10, as prognostically relevant and represent the first comprehensive study exploring the clinical implications of the CMML inflammatory state.
Assuntos
Biomarcadores Tumorais/genética , Citocinas/sangue , Mediadores da Inflamação/sangue , Leucemia Mielomonocítica Crônica/patologia , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Leucemia Mielomonocítica Crônica/sangue , Leucemia Mielomonocítica Crônica/classificação , Leucemia Mielomonocítica Crônica/genética , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
The impact of bone marrow fibrosis grade on the prognosis of patients with chronic myelomonocytic leukemia (CMML) remains controversial. Therefore, we examined the records of 82 patients diagnosed with CMML at our institution and summarized baseline characteristics and molecular profiles by subgroups of absent or mild (grades 0/1) and moderate (grade 2) fibrosis. Cox proportional hazards models were constructed to assess the prognostic significance of fibrosis grade. Grade 2 fibrosis was identified in 63 patients (76.8%), grade 1 in 16 patients (19.5%), and grade 0 in 3 patients (3.7%). Grade 2 fibrosis was associated with reduced hemoglobin levels (median 9.75 vs 11.0 g/dL in grade 0/1; p = 0.04) and increased percentages of ringed sideroblasts (7.5 vs 0%; p = 0.008). In multivariable analysis, grade 2 fibrosis was an independent predictor of poor overall survival (OS; 95% CI 1.32-6.35; HR 2.90; p = 0.008), but not event-free survival (EFS; 95% CI 0.62-2.67; HR 1.28; p = 0.50). Absolute neutrophil count (ANC) was found to impact OS (95% CI 1.01-1.09; HR 1.05; p = 0.009), while both ANC (95% CI 1.00-1.07; HR 1.04; p = 0.04) and peripheral blood blast percentage (95% CI 1.02-1.32; HR 1.16; p = 0.02) impacted EFS. These results implicate fibrosis grade is an important indicator of prognosis, with high-grade fibrosis predicting inferior survival. Given the prevalence of marrow fibrosis in CMML, fibrosis grading should be incorporated into prognostic assessment and therapeutic decision-making.
Assuntos
Medula Óssea/patologia , Leucemia Mielomonocítica Crônica/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Intervalo Livre de Doença , Feminino , Fibrose , Humanos , Estimativa de Kaplan-Meier , Leucemia Mielomonocítica Crônica/sangue , Leucemia Mielomonocítica Crônica/genética , Leucemia Mielomonocítica Crônica/mortalidade , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Mutação , Neutrófilos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaAssuntos
Sistema Nervoso Central/patologia , Leucemia Mielomonocítica Crônica/terapia , Antimetabólitos Antineoplásicos/uso terapêutico , Citarabina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia Mielomonocítica Crônica/sangue , Leucemia Mielomonocítica Crônica/líquido cefalorraquidiano , Leucocitose/sangue , Leucocitose/líquido cefalorraquidiano , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Monócitos/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Accumulation of classical monocytes CD14++ CD16- (also called MO1) ≥ 94% can accurately distinguish chronic myelomonocytic leukemia (CMML) from reactive monocytosis. The HematoFlow™ solution, able to quantify CD16 negative monocytes, could be a useful tool to manage monocytosis which remains a common issue in routine laboratories. METHODS: Classical monocytes were quantified from 153 whole blood samples collected on EDTA using both flow cytometry methods, either MO1 percentage determination by the multiparameter assay previously published and regarded here as the reference method, or CD16 negative monocyte percentage determination by the means of HematoFlow™. RESULTS: Both methods of classical monocyte percentage determination were highly and significantly correlated (r = 0.87, P < 0.0001). The HematoFlow™ solution leant toward an overestimation of the genuine classical monocyte percentages obtained by the reference method. Percentages of CD16 negative monocytes provided by HematoFlow were higher than 94% for all the 73 patients displaying classical monocytes MO1 found ≥94% by the reference method, indicating a sensitivity of 100%. Furthermore, the calculation of CD16 negative monocyte percentage can be easily computerized and integrated to the middleware. CONCLUSIONS: We propose a new application of the Hematoflow™ solution that can be used as a flag system for monocytosis management and CMML detection. © 2017 International Clinical Cytometry Society.
Assuntos
Citometria de Fluxo , Leucemia Mielomonocítica Crônica/diagnóstico , Humanos , Leucemia Mielomonocítica Crônica/sangue , Sensibilidade e Especificidade , SoluçõesRESUMO
RATIONALE: Thrombocytopenia in chronic myelomonocytic leukemia (CMML) is usually attributed to impaired marrow production resulting from cytotoxic drug use or CMML itself ("CMML-induced thrombocytopenia"). In very rare cases, immune thrombocytopenia (ITP) can be a complication of CMML ("CMML-associated ITP"). However, treatment of severe thrombocytopenia in patients with CMML is still a challenge. PATIENT CONCERNS: Case 1 was a 61-year-old female patient admitted to our hospital because of skin petechiae and purpura for 6 days. She had increased monocyte cell count (1.82â×â10/L), markedly decreased platelet count (2â×â10/L), hypercellularity of the megakaryocyte lineage with many immature megakaryocytes, and ZRSR2(zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2) mutation. She failed to the treatment of corticosteroids, intravenous immunoglobulin (IVIg), TPO (thrombopoietin), and cyclosporin A (CsA). Case 2 was a 72-year-old female patient with thrombocytosis and monocytosis for 4 years, and thrombocytopenia for 6 months. After 10 courses of decitabine therapy, she had a persistent severe thrombocytopenia and decreased number of megakaryocytes, TET2 (tet methylcytosine dioxygenase 2) and SRSF2 (serine and arginine rich splicing factor 2) mutations were detected. She was dependent on platelet transfusion. DIAGNOSES: Case 1 was diagnosed as CMML-associated ITP, and case 2 as CMML with decitabine therapy-induced thrombocytopenia. INTERVENTIONS: Both patients were treated with eltrombopag. OUTCOMES: In both patients, the platelet counts returned to the normal within 1 week after eltrombopag therapy. The platelet count in case 1 patient remained stable at 141-200â×â10/L for 20 months with stopping therapy for 3 months. In case 2 patient, eltrombopag was stopped 1 month later. Her platelet count decreased to 41â×â10/L, but was stable at â¼30â×â10/L for 3 months with platelet transfusion independency for 12 months. Both patients had no adverse effects with eltrombopag. LESSONS: CMML-associated ITP is very rare and easily misdiagnosed. To the best of our knowledge, case 1 is the first reported case of the successful treatment of CMML-associated ITP with eltrombopag. Both CMML-associated ITP and decitabine therapy-induced thrombocytopenia in these 2 patients were highly sensitive and safe to eltrombopag therapy.
Assuntos
Azacitidina/análogos & derivados , Benzoatos/administração & dosagem , Hidrazinas/administração & dosagem , Leucemia Mielomonocítica Crônica , Púrpura Trombocitopênica Idiopática , Pirazóis/administração & dosagem , Trombocitopenia , Trombopoetina/agonistas , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Azacitidina/efeitos adversos , Proteínas de Ligação a DNA/genética , Decitabina , Dioxigenases , Monitoramento de Medicamentos , Feminino , Fármacos Hematológicos/administração & dosagem , Humanos , Leucemia Mielomonocítica Crônica/sangue , Leucemia Mielomonocítica Crônica/complicações , Leucemia Mielomonocítica Crônica/diagnóstico , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Pessoa de Meia-Idade , Mutação , Proteínas Nucleares/genética , Contagem de Plaquetas/métodos , Proteínas Proto-Oncogênicas/genética , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/etiologia , Púrpura Trombocitopênica Idiopática/fisiopatologia , Ribonucleoproteínas/genética , Fatores de Processamento de Serina-Arginina/genética , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Trombocitopenia/tratamento farmacológico , Trombocitopenia/fisiopatologia , Resultado do TratamentoAssuntos
Aberrações Cromossômicas , Citoplasma/ultraestrutura , Amplificação de Genes , Genes myc/genética , Corpos de Inclusão/ultraestrutura , Leucemia Mielomonocítica Crônica/genética , Leucemia Mielomonocítica Crônica/patologia , Idoso de 80 Anos ou mais , Células da Medula Óssea/patologia , Células da Medula Óssea/ultraestrutura , Humanos , Cariótipo , Leucemia Mielomonocítica Crônica/sangue , MasculinoAssuntos
Leucemia Mielomonocítica Crônica/patologia , Contagem de Leucócitos , Monócitos/patologia , Síndromes Mielodisplásicas/classificação , Corticosteroides/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/farmacologia , Medula Óssea/patologia , Progressão da Doença , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Inflamação/sangue , Inflamação/tratamento farmacológico , Leucemia Mielomonocítica Crônica/sangue , Masculino , Pessoa de Meia-Idade , Monócitos/classificação , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/patologia , Risco , Adulto JovemRESUMO
Chronic Myelomonocytic Leukemia is a chronic myeloid neoplasm occurring mostly in the elderly with overlapping features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) characterized by chronic monocytosis. Recent progresses in the molecular and cellular pathogenesis of CMML have stirred a renewed interest in this clinically heterogeneous disorder. Here, we review the recent progresses in the biology of CMML and how it affects its current and future clinical management.
Assuntos
Leucemia Mielomonocítica Crônica , Síndromes Mielodisplásicas , Humanos , Leucemia Mielomonocítica Crônica/sangue , Leucemia Mielomonocítica Crônica/genética , Leucemia Mielomonocítica Crônica/terapia , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/terapiaAssuntos
Proteínas de Fusão bcr-abl , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mielomonocítica Crônica , Feminino , Proteínas de Fusão bcr-abl/sangue , Proteínas de Fusão bcr-abl/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mielomonocítica Crônica/sangue , Leucemia Mielomonocítica Crônica/diagnóstico , Leucemia Mielomonocítica Crônica/genética , Leucemia Mielomonocítica Crônica/patologia , Pessoa de Meia-IdadeAssuntos
Leucemia Mielomonocítica Crônica , Monócitos , Síndromes Mielodisplásicas , Feminino , Proteínas Ligadas por GPI/sangue , Proteínas Ligadas por GPI/imunologia , Humanos , Leucemia Mielomonocítica Crônica/sangue , Leucemia Mielomonocítica Crônica/imunologia , Leucemia Mielomonocítica Crônica/patologia , Receptores de Lipopolissacarídeos/sangue , Receptores de Lipopolissacarídeos/imunologia , Masculino , Monócitos/imunologia , Monócitos/metabolismo , Monócitos/patologia , Monocinas/sangue , Monocinas/imunologia , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/imunologia , Síndromes Mielodisplásicas/patologia , Receptores de IgG/sangue , Receptores de IgG/imunologiaRESUMO
The relationship between primary hematologic disease and rheumatologic manifestations is well known, especially acute lymphocytic leukemia, lymphomas, plasma cell dyscrasias and myelodysplastic syndrome (MDS). Currently, more has been described about autoimmune manifestations in chronic myelomonocytic leukemia (CMML). Many different clinical scenarios may lead a patient with MDS/CMML initially to seek a rheumatological unit. Autoimmune features such as polymyalgia rheumatic symptoms, myositis, neutrophilic dermatosis, cutaneous vasculitis and positive antinuclear antibodies (ANA) are some examples of clinical presentation of MDS/CMML. Moreover, peripheral cytopenias are a common initial presentation both for systemic lupus erythematous (SLE) and MDS/CMML. The aim of this study was to describe a case of an elderly woman with thrombocytopenia and positivity of antibodies to anti-extractable nuclear antigens (anti-ENA) as initial manifestation of CMML mimicking SLE, and to present some clues that encourage the clinician to perform a bone marrow study in such a clinical scenario.
Assuntos
Anticorpos Antinucleares/sangue , Leucemia Mielomonocítica Crônica/sangue , Lúpus Eritematoso Sistêmico/sangue , Trombocitopenia/sangue , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Biomarcadores/sangue , Exame de Medula Óssea , Diagnóstico Diferencial , Feminino , Hemólise , Humanos , Leucemia Mielomonocítica Crônica/diagnóstico , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Leucemia Mielomonocítica Crônica/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Valor Preditivo dos Testes , Trombocitopenia/diagnóstico , Trombocitopenia/imunologiaAssuntos
Rearranjo Gênico , Leucemia Mielomonocítica Crônica/genética , Monócitos , Transtornos Mieloproliferativos/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Intervalo Livre de Doença , Registros Eletrônicos de Saúde , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/uso terapêutico , Leucemia Mielomonocítica Crônica/sangue , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Transtornos Mieloproliferativos/sangue , Transtornos Mieloproliferativos/tratamento farmacológico , Resultado do TratamentoRESUMO
We report on a familial Mediterranean fever (FMF) patient homozygous for p.M694V in the MEFV gene who developed chronic myelomonocytic leukemia (CMML) leading to an uncontrolled and fatal inflammatory syndrome. Plasma levels of IL-6 and IL-18 were found to be very high, as compared to healthy controls and CMML-free FMF patients.Our study unveils the interplay between two different disorders involving the same target cells, suggesting that in myelodysplasia with inflammatory manifestations, mutations in genes causing autoinflammatory syndromes, like MEFV, can be present and thus could be sought. Early chemotherapy with interleukin inhibitors could be proposed in such unusual situations.