RESUMO
The WHO classification provides the best diagnostic approach to myelodysplastic syndromes (MDS). However, biologic and analytic limitations have emerged in the criteria currently adopted to establish the diagnosis and to classify MDS. The provisional category of idiopathic cytopenia of undetermined significance (ICUS) has been proposed to describe patients in whom MDS is possible but not proven. To formulate a diagnosis of ICUS, a thorough diagnostic work-up is required and repeated tests should be performed to reach a conclusive diagnosis. Recent studies provided consistent evidence of age-related hematopoietic clones (clonal hematopoiesis of indeterminate potential; CHIP), driven by mutations of genes that are recurrently mutated in myeloid neoplasms and associated with increase in the risk of hematologic cancer. A subset of mutated genes, mainly involved in epigenetic regulation, are likely initiating lesions driving the expansion of a premalignant clone. However, in a fraction of subjects the detected clone may be a small malignant clone expanding under the drive of the detected and additional undetected mutations. In addition, several experimental evidences suggest the potential relevance of an abnormal bone marrow environment in the selection and evolution of hematopoietic clones in MDS. The spreading of massively parallel sequencing techniques is offering translational opportunities in the clinical approach to myeloid neoplasms. Although several issues remain to be clarified, targeted gene sequencing may be of potential value in the dissection between clonal myelodysplasia, nonclonal cytopenia, and clonal hematopoiesis arising upon aging or in the context of acquired marrow failure.
Assuntos
Neoplasias Hematológicas/diagnóstico , Hematopoese , Síndromes Mielodisplásicas/diagnóstico , Pancitopenia/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Anemia Aplástica/classificação , Anemia Aplástica/diagnóstico , Medula Óssea/patologia , Transformação Celular Neoplásica , Epigênese Genética , Feminino , Neoplasias Hematológicas/classificação , Humanos , Pessoa de Meia-Idade , Mutação , Síndromes Mielodisplásicas/classificação , Pancitopenia/classificação , Prevalência , RiscoAssuntos
Síndromes Mielodisplásicas/diagnóstico , Idoso de 80 Anos ou mais , Anemia Aplástica/classificação , Anemia Aplástica/diagnóstico , Anemia Aplástica/patologia , Azacitidina/análogos & derivados , Azacitidina/uso terapêutico , Medula Óssea/patologia , Exame de Medula Óssea , Proliferação de Células , Transformação Celular Neoplásica/patologia , Decitabina , Diagnóstico Diferencial , Progressão da Doença , Hematopoese/fisiologia , Humanos , Lenalidomida , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patologia , Masculino , Síndromes Mielodisplásicas/classificação , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/patologia , Prognóstico , Talidomida/análogos & derivados , Talidomida/uso terapêuticoAssuntos
Anemia Aplástica/diagnóstico , Síndromes Mielodisplásicas/diagnóstico , Anemia Aplástica/classificação , Doenças da Medula Óssea , Transtornos da Insuficiência da Medula Óssea , Diagnóstico Diferencial , Hemoglobinúria Paroxística/diagnóstico , Humanos , Medicina Interna , Síndromes Mielodisplásicas/classificação , Guias de Prática Clínica como AssuntoRESUMO
Distinguishing hypoplastic myelodysplastic syndrome from aplastic anemia (AA) is challenging. In the present study, Japanese and Chinese pediatric hematologists and pathologists conducted a joint review of bone marrow (BM) smears and trephine biopsies in 100 children with acquired BM failure syndrome, using the criteria proposed in the 2008 edition of the World Health Organization classification of hematopoietic and lymphoid tissues. The final consensus for the diagnoses of 100 children was AA in 29 patients, refractory cytopenia of childhood (RCC) in 58 patients, and refractory cytopenia with multilineage dysplasia (RCMD) in 13 patients. No significant differences between Japanese and Chinese children were found with regards to clinical and laboratory findings, or the distribution of diagnoses. Patients with RCC/RCMD showed milder disease severity and BM hypocellularity than those with AA. To establish the provisional entities for RCC, it is essential to prospectively compare the clinical outcomes between AA and RCC groups in a large number of patients.
Assuntos
Anemia Aplástica/diagnóstico , Anemia Refratária/diagnóstico , Povo Asiático , Hemoglobinúria Paroxística/diagnóstico , Adolescente , Anemia Aplástica/classificação , Anemia Refratária/classificação , Doenças da Medula Óssea , Transtornos da Insuficiência da Medula Óssea , Criança , Pré-Escolar , China , Diagnóstico Diferencial , Feminino , Hemoglobinúria Paroxística/classificação , Humanos , Lactente , Japão , Masculino , Organização Mundial da SaúdeRESUMO
Hypoplastic BM disorders in children and adolescents comprise a broad spectrum of disorders. Acquired severe aplastic anemia (SAA), refractory cytopenia of childhood (RCC), a subtype of myelodysplastic syndrome (MDS), and inherited BM failure (IBMF) disorders are the main and most difficult hematological differential diagnoses. Whereas IBMF disorders can often be diagnosed by their clinical features and/or underlying genetic aberrations, the morphological distinction between SAA and hypocellular RCC has been controversial. The histopathological pattern of RCC consists of islands of immature erythroid precursors accompanied by sparsely distributed granulocytic cells. Megakaryocytes are significantly decreased or absent and, rarely, micromegakaryocytes are detected on immunohistochemistry. Because fatty tissue between areas of hematopoiesis can mimic SAA, 2 biopsies are recommended to facilitate the detection of representative BM spaces. Recent data indicate that the response to immunosuppressive therapy is inferior in RCC compared with SAA. Furthermore, approaches to allogeneic hematopoietic transplantation differ. Controlled prospective clinical studies in patients with hypoplastic BM failure disorders will require comprehensive guidelines for diagnosing SAA, RCC, and the different IBMF disorders.
Assuntos
Anemia Aplástica/classificação , Síndromes Mielodisplásicas/classificação , Anemia Aplástica/diagnóstico , Anemia Aplástica/patologia , Anemia Aplástica/terapia , Criança , Diagnóstico Diferencial , Doenças Genéticas Inatas/patologia , Humanos , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/terapiaRESUMO
BACKGROUND: Intracerebral hemorrhage (ICH) is an unusual but serious complication of bleeding disorders. ICH is believed to follow thrombocytopenia, alterations in coagulation, and vascular fragility. Information regarding its distribution is nonconclusive, and the mechanism of bleeding is not fully understood. The aim of this study was to examine the clinical and neuroimaging features of ICH in patients with bleeding disorders to predict risk factors for this condition. METHODS: All cases of ICH diagnosed from 1987 to 2004 were retrospectively identified using the centralized database of our institution. Cases were included whenever ICH was caused by a primary hematologic disorder. The clinical characteristics, neuroimages, and outcome were analyzed. RESULTS: A total of 31 patients were identified. ICH was the initial presentation of the bleeding disorder in 9 patients. Overall, 71% had systemic bleeding concurrent to the ICH. All patients had altered mental status. In 45.2% of the patients simultaneous intracranial hemorrhages were found. Eight patients had recurrent ICH. Severe thrombocytopenia (platelet count < 10,000/mm(3)) was present in 41% and very low platelets (=1000/mm(3)) in 3%. Death occurred in 71%. CONCLUSIONS: Multiple ICH is not an unusual presentation in patients with primary bleeding disorders developing brain hemorrhage. Although low platelet counts can be blamed for the bleeding, factors different from thrombocytopenia should be considered as the principal mechanism. The best predictor of cerebral bleeding is the presence of systemic bleeding.
Assuntos
Hemorragia Cerebral/etiologia , Transtornos Hemorrágicos/complicações , Adolescente , Adulto , Idoso , Anemia Aplástica/classificação , Anemia Aplástica/complicações , Anemia Aplástica/epidemiologia , Hemorragia Cerebral/sangue , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/patologia , Feminino , Transtornos Hemorrágicos/sangue , Transtornos Hemorrágicos/diagnóstico , Transtornos Hemorrágicos/epidemiologia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/epidemiologia , Neoplasias/sangue , Neoplasias/complicações , Neoplasias/epidemiologia , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/epidemiologia , Recidiva , Estudos Retrospectivos , Fatores de Risco , Trombocitopenia/sangue , Trombocitopenia/complicações , Trombocitopenia/epidemiologia , Resultado do TratamentoRESUMO
Aplastic anemia (AA) is a disorder characterized by the presence of pancytopenia and a hypocellular bone marrow. Acquired pure red cell aplasia (PRCA), a part of a unique form of AA, is a rare condition of profound anemia characterized by the absence of reticulocytes and the virtual absence of erythroid precursors in the bone marrow. AA can be effectively treated by either stem cell transplantation or immunosuppressive therapy. However, PRCA has so far been treated by several different regimens which are largely empirically selected since so little control data are available. This issue focuses on the current progress in the treatment of acquired AA and PRCA.
Assuntos
Anemia Aplástica , Aplasia Pura de Série Vermelha , Corticosteroides/administração & dosagem , Anemia Aplástica/classificação , Anemia Aplástica/diagnóstico , Anemia Aplástica/terapia , Soro Antilinfocitário/administração & dosagem , Transplante de Medula Óssea , Ciclofosfamida/administração & dosagem , Ciclosporina/administração & dosagem , Quimioterapia Combinada , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Imunossupressores/administração & dosagem , Troca Plasmática , Aplasia Pura de Série Vermelha/classificação , Aplasia Pura de Série Vermelha/diagnóstico , Aplasia Pura de Série Vermelha/terapia , Índice de Gravidade de DoençaAssuntos
Criança , Humanos , Anemia Aplástica/etiologia , Anemia Aplástica/terapia , Imunossupressores/uso terapêutico , Anemia Aplástica/classificação , Transplante de Medula Óssea , Benzeno/efeitos adversos , Ciclofosfamida/uso terapêutico , Cloranfenicol/efeitos adversos , Herpesvirus Humano 4 , Prognóstico , Vírus de Hepatite/patogenicidadeRESUMO
OBJECTIVE: To explore the relationship between CD8+ T-cell CD28 molecular expression in peripheral blood and TCM type in patients with chronic aplastic anemia (CAA). METHODS: Using flow cytometry to detect the CD28 expression in 45 in-patients or out-patients and 24 healthy subjects for control. And the relation with TCM type was analyzed from the immunological aspect. RESULTS: (1) The levels of CD8, CD28, CD8+ CD28+ expression and CD8+ CD28+/CD8+ CD28- were all higher in the CAA patients than those in the healthy subjects (P < 0.05 or P < 0.01). (2) The levels of CD28, CD8+ CD28+ expression and CD8+ CD28+/CD8+ CD28- were all higher in the CAA patients of Shen-Yin deficiency type than those in the CAA patients of Shen-Yang deficiency type (P < 0.05 or P < 0.01). CONCLUSION: (1) The abnormal high expression of peripheral blood co-stimulatory molecules CD28 suggested CD28 disorder may play an important role in immuno-pathogenesis of CAA. (2) The levels of peripheral CD28, CD8+ CD28+ expression and CD8+ CD28+/CD8+ CD28- can be taken as an objective indexes for TCM typing of CAA, which was disordered more severe in patients of Shen-Yin deficiency type than in those of Shen-Yang deficiency type.
Assuntos
Anemia Aplástica/diagnóstico , Antígenos CD28/biossíntese , Linfócitos T CD8-Positivos/imunologia , Medicina Tradicional Chinesa , Adulto , Anemia Aplástica/classificação , Anemia Aplástica/imunologia , Doença Crônica , Diagnóstico Diferencial , Humanos , Nefropatias/imunologia , Masculino , Deficiência da Energia Yang/imunologia , Deficiência da Energia Yin/imunologiaAssuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea , Imunossupressores/uso terapêutico , Adulto , Anabolizantes/uso terapêutico , Anemia Aplástica/classificação , Anemia Aplástica/diagnóstico , Soro Antilinfocitário/uso terapêutico , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Medicina Baseada em Evidências , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Japão , Metenolona/uso terapêutico , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de DoençaRESUMO
Anaemia is not a disease in itself. It is a sign of a single or multiple diseases. Anaemia is said to exist when the haemoglobin concentration is below normal for the age and sex of an individual. The synthesis and normal circulatory level of haemoglobin in any given individual depend on factors such as an adequate supply of haemopoietic nutrients, normal functioning of bone marrow, and proper utilization of haemoglobin. Based on these factors anemia can be broadly grouped into three categories: 1. Anaemia due to lack of haemopoietic nutrients (nutritional anemia) 2. Anaemia due to bone marrow dysfunction (aplastic anaemia) 3. Anaemia due to excessive breakdown of red blood cells (haemolytic anaemia) (AU)
Assuntos
Humanos , Anemias Nutricionais/complicações , Anemia Megaloblástica/classificação , Anemia Megaloblástica/diagnóstico , Anemia Megaloblástica/prevenção & controle , Anemia Aplástica/classificação , Anemia Aplástica/etiologia , Anemia Aplástica/diagnóstico , Anemia Aplástica/tratamento farmacológico , Hemólise/efeitos dos fármacos , Anemia Hemolítica/complicações , Anemia Hemolítica/diagnóstico , Anemia Hemolítica/etiologia , Hemoglobinúria Paroxística/diagnóstico , Talassemia/diagnóstico , Talassemia/etiologiaRESUMO
The main cause of aplastic anaemia remains elusive. Germline mutations in the gene encoding the RNA component of telomerase (hTR) have been seen in the autosomal dominant form of dyskeratosis congenita--an inherited syndrome characterised by aplastic anaemia. By screening the hTR gene, we identified mutations in two of 17 patients with idiopathic aplastic anaemia, three of 27 patients with constitutional aplastic anaemia, but in none of 214 normal controls (p<0.0001). Furthermore, patients with hTR mutations had significantly shorter telomeres than age-matched controls (p=0.027). These data indicate that, in a subset of patients with aplastic anaemia, the disorder might be associated with a genetic lesion in the telomere maintenance pathway.
Assuntos
Anemia Aplástica/genética , Reação em Cadeia da Polimerase/métodos , RNA/genética , Telomerase/genética , Adolescente , Adulto , Anemia Aplástica/classificação , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação/genética , RNA/isolamento & purificação , Telomerase/isolamento & purificaçãoRESUMO
In most human cells, the average length of telomere repeats at the ends of chromosomes provides indirect information about their mitotic history. To study the turnover of stem cells in patients with bone marrow failure syndromes, the telomere length in peripheral blood granulocytes and lymphocytes from patients with aplastic anemia (AA, n = 56) and hemolytic paroxysmal nocturnal hemoglobinuria (n = 6) was analyzed relative to age-matched controls by means of fluorescence in situ hybridization and flow cytometry. The telomere lengths in granulocytes from patients with AA were found to be significantly shorter than those in age-adjusted controls (P =.001). However, surprisingly, telomere length in granulocytes from AA patients who had recovered after immunosuppressive therapy did not differ significantly from controls, whereas untreated patients and nonresponders with persistent severe pancytopenia showed marked and significant telomere shortening. These results support extensive proliferation of hematopoietic stem cells in subgroups of AA patients. Because normal individuals show significant variation in telomere length, individual measurements in blood cells from AA patients may be of limited value. Whether sequential telomere length measurements can be used as a prognostic tool in this group of disorders remains to be clarified. (Blood. 2001;97:895-900)
Assuntos
Anemia Aplástica/patologia , Granulócitos/ultraestrutura , Hemoglobinúria Paroxística/patologia , Telômero/ultraestrutura , Adolescente , Adulto , Idoso , Envelhecimento/genética , Anemia Aplástica/classificação , Anemia Aplástica/tratamento farmacológico , Anemia Aplástica/genética , Criança , Pré-Escolar , Resistência a Medicamentos , Feminino , Citometria de Fluxo , Granulócitos/classificação , Hemoglobinúria Paroxística/genética , Humanos , Imunossupressores/uso terapêutico , Hibridização in Situ Fluorescente , Lactente , Masculino , Pessoa de Meia-IdadeAssuntos
Doenças Hematológicas , Anemia Aplástica/classificação , Anemia Aplástica/congênito , Anemia Aplástica/fisiopatologia , Anemia Aplástica/terapia , Criança , Eritroblastos , Eritropoese , Doenças Hematológicas/congênito , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/fisiopatologia , Doenças Hematológicas/terapia , Hematopoese , Humanos , Lactente , Neutropenia/diagnóstico , Neutropenia/terapiaRESUMO
The authors evaluated results of treatment of 106 children with acquired aplastic anemia. The patients were divided into 3 groups depending on the severity of their disease. Thirty-nine patients were classified as very severe, 30 as severe and 37 as non-severe according to the modified Camitta criteria. Among them, 47 children were treated with oxymetholone and prednisolone. In this group 32 died. Antilymphocyte globulin (ALG) was given to 48 patients and 20 received cyclosporin A (CsA). The results obtained by these two methods are nearly the same and 5 year survival was 61% and 59% respectively. Bone marrow was transplanted in only one child, who is still in complete remission. Statistical analysis showed a steady increase in incidence of aplastic anemia in the years 1987-1989, which might coincide with the Czarnobyl explosion. However, further research is required to prove this point.