RESUMEN
Karyotype complexity has major prognostic value in many malignancies. There is no consensus on the definition of a complex karyotype, and the prognostic impact of karyotype complexity differs from one disease to another. Due to the importance of the complex karyotype in the prognosis and treatment of several hematological diseases, the Francophone Group of Hematological Cytogenetics (Groupe Francophone de Cytogénétique Hématologique, GFCH) has developed an up-to-date, practical document for helping cytogeneticists to assess complex karyotypes in these hematological disorders. The evaluation of karyotype complexity is challenging, and it would be useful to have a consensus method for counting the number of chromosomal abnormalities (CAs). Although it is not possible to establish a single prognostic threshold for the number of CAs in all malignancies, a specific consensus prognostic cut-off must be defined for each individual disease. In order to standardize current cytogenetic practices and apply a single denomination, we suggest defining a low complex karyotype as having 3 CAs, an intermediate complex karyotype as having 4 CAs, and a highly complex karyotype as having 5 or more CAs.
Asunto(s)
Neoplasias Hematológicas , Hematología , Aberraciones Cromosómicas , Análisis Citogenético/métodos , Citogenética , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Humanos , Cariotipo , Pronóstico , Sociedades MédicasRESUMEN
Immunosuppressive treatment is a disease-modifying therapy for lower-risk myelodysplastic syndromes (MDS). However, IST is relatively rarely used and long-term outcomes of patients are seldom reported. We retrospectively studied outcomes of 20 patients with lower-risk non del 5q MDS with transfusion dependency, with horse or rabbit antithymocyte globulin⯱â¯ciclosporine A, and frontline eltrombopag in two of them. IPSS-R was low, intermediate and high in 30%, 55% and 10% of the patients, respectively. Fifty-five percent of the patients had hypocellular bone marrow (BM). Baseline mutations were detected in 31.5% of the patients and were more frequent in patients with normo/hypercellular MDS than in patients with hypocellular MDS. Transfusion independence rate for both red blood cells (RBC) and platelets was achieved in 45% of patients. RBC transfusion duration ≤6 months, B-cell counts >0.2â¯G/L and, marginally, BM blasts ≤2% were associated with higher transfusion independence rate. Age and cellularity did not influence the response rate. Median transfusion independence duration was 53 months. Cumulative incidence of progression to a more aggressive myeloid disease was 0 in patients without baseline mutations and 33% in patients with baseline mutations (Pâ¯=â¯.008). Median progression-free and overall survival after treatment onset and median overall survival after loss of transfusion independence were 45.5 months, 68 months and not reached, respectively. In conclusion, antithymocyte globulin⯱â¯ciclosporine A results in durable responses in MDS, irrespective of age, in patients with lower-risk disease without B-cell lymphopenia and treated early in the course of the disease.
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Suero Antilinfocítico/uso terapéutico , Ciclosporina/uso terapéutico , Inmunosupresores/uso terapéutico , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/genética , Anciano , Análisis Mutacional de ADN , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
A retrospective cytogenetic study of acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS) was conducted by the Groupe Francophone de Cytogénétique Hématologique (GFCH) to evaluate the structural abnormalities of chromosome 5 associated with other chromosomal abnormalities, in particular of chromosome 7, in these pathologies. In all, 110 cases of AML/MDS were recruited based on the presence of chromosome 5 abnormalities under conventional cytogenetics and supplemented by a systematic fluorescence in situ hybridization study of chromosomes 5 and 7. The abnormalities of the long arm of chromosome 5 (5q) were deletions of various sizes and sometimes cryptic. The 5q abnormalities were associated with translocations in 54% of cases and were simple deletions in 46%. In 68% of cases, 5q deletions were associated with chromosome 7 abnormalities, and 90% of these presented a complex karyotype. Of the 110 patients, 28 had a hematopoietic disorder secondary to chemotherapy, radiotherapy, or both. Among 82 patients with de novo AML/MDS, 63 were older than 60 years. Chromosomal abnormalities often associated hypodiploidy and chromosome 5 and 7 abnormalities in complex karyotypes, features resembling those of secondary hemopathies. Systematic investigation of the exposure to mutagens and oncogenes is thus essential to specify the factors potentially involved in MDS/AML with 5q abnormalities.
Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos Par 5 , Cromosomas Humanos Par 7 , Leucemia Mieloide/genética , Síndromes Mielodisplásicos/genética , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Deleción Cromosómica , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Neoplasias Inducidas por Radiación , Translocación GenéticaRESUMEN
The human AML1 gene (also named CBFA2 or RUNX1), located in the 21q22 chromosomal band, encodes for one of the two subunits forming a heterodimeric transcription factor, the human core binding factor (CBF). AML1 protein contains a highly evolutionary conserved domain of 128 amino acids called runt domain, responsible for both heterodimerization with the beta subunit of CBF and for DNA binding. AML1 is normally expressed in all hematopoietic lineages and acts to regulate the expression of various genes specific to hematopoiesis playing a pivotal role in myeloid differentiation. AML1 is one of the genes most frequently deregulated in leukemia through different mechanisms including translocation, mutation and amplification. Translocations lead to the formation of fusion genes encoding for chimerical proteins such as AML1-ETO which induces leukemogenesis. Recently, new mechanisms of AML1 deregulation by point mutations or amplification have been reported. To our knowledge, 51 patients (among 805 studied) with AML1 point mutations have been described. Forty of them have acute myeloid leukemia (AML) most often M0 AML. In this subtype of AML, the frequency of AML1 mutation is significantly higher; 21.5% of patients mutated (34/158). Mutations have also been found with lower frequency in other FAB subtype AML (6 cases), in myeloproliferative disorders (6 cases), in myelodysplastic syndrome (3 cases) and rarely in acute lymphoblastic leukemia (1 case). AML1 gene amplification has been found essentially in childhood ALL (12 cases) and more rarely in myeloid malignancies (4 cases). Here, we reviewed all these cases of AML1 point mutations and amplification and focused on the mechanisms of AML1 deregulation induced by these alterations.
Asunto(s)
Proteínas de Unión al ADN/genética , Leucemia Mieloide/genética , Mutación , Síndromes Mielodisplásicos/genética , Proteínas Proto-Oncogénicas , Factores de Transcripción/genética , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Cromosomas Humanos Par 21 , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Proteínas de Unión al ADN/metabolismo , Femenino , Amplificación de Genes , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Proteína 1 Compañera de Translocación de RUNX1 , Factores de Transcripción/metabolismo , Translocación GenéticaRESUMEN
Imatinib mesylate (Gleevec), an inhibitor of the BCR-ABL tyrosine kinase, was introduced recently into the therapy of chronic myeloid leukemia (CML). Several cases of emergence of clonal chromosomal abnormalities after therapy with imatinib have been reported, but their incidence, etiology and prognosis remain to be clarified. We report here a large series of 34 CML patients treated with imatinib who developed Philadelphia (Ph)-negative clones. Among 1001 patients with Ph-positive CML treated with imatinib, 34 (3.4%) developed clonal chromosomal abnormalities in Ph-negative cells. Three patients were treated with imatinib up-front. The most common cytogenetic abnormalities were trisomy 8 and monosomy 7 in twelve and seven patients, respectively. In 15 patients, fluorescent in situ hybridization with specific probes was performed in materials archived before the initiation of imatinib. The Ph-negative clone was related to previous therapy in three patients, and represented a minor pre-existing clone that expanded after the eradication of Ph-positive cells with imatinib in two others. However, in 11 patients, the new clonal chromosomal abnormalities were not detected and imatinib may have had a direct effect. No myelodysplasia was found in our cohort. With a median follow-up of 24 months, one patient showed CML acceleration and two relapsed.
Asunto(s)
Aberraciones Cromosómicas , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/genética , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/patología , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Adulto , Anciano , Aneuploidia , Benzamidas , Cromosomas Humanos Par 7 , Cromosomas Humanos Par 8 , Células Clonales/patología , Femenino , Humanos , Mesilato de Imatinib , Incidencia , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
Systemic mastocytosis is characterized by abnormal mast cell proliferation in different organs. The 2001 consensus classification distinguishes in separate categories indolent systemic mastocytosis, systemic mastocytosis with concomitant blood disease, aggressive systemic mastocytosis and mast cell leukemia. Clinical manifestations are caused by tissue infiltration by proliferating mastocytes and by release of mediators. The principal organs affected are the skin, bones, digestive tract, liver, spleen and lymph nodes. Diagnosis of mastocytosis is based on appropriate stains (Giemsa, toluidine blue) and immunophenotype features (tryptase, CD117, also known as c-KIT and stem cell factor receptor). Serum tryptase levels reflect the total mast cell burden. Treatment must prevent release of mast cell mediators (histamine antagonists, cromolyn sodium, corticosteroids, or leukotriene-receptor inhibitors), limit bone involvement (bisphosphonates) and reduce the number of circulating mast cells (interferon, cladribine, or tyrosine kinase inhibitors). Enhanced understanding of the pathogenic mechanisms (mutation of c-kit and platelet-derived growth factor receptor alpha has led to the development of targeted treatments, including new inhibitors of tyrosine kinase and of nuclear factor Kappa B.
Asunto(s)
Mastocitosis Sistémica , Benzamidas , Biomarcadores , Huesos/patología , Diferenciación Celular , División Celular , Cladribina/uso terapéutico , Difosfonatos/uso terapéutico , Rubor/etiología , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Liberación de Histamina/efectos de los fármacos , Mesilato de Imatinib , Interferón-alfa/uso terapéutico , Antagonistas de Leucotrieno/uso terapéutico , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/tratamiento farmacológico , Mastocitosis Sistémica/etiología , Mastocitosis Sistémica/patología , Mastocitosis Sistémica/fisiopatología , Proteínas de Fusión Oncogénica , Piperazinas/uso terapéutico , Pronóstico , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/fisiología , Pirimidinas/uso terapéutico , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/fisiología , Serina Endopeptidasas/sangre , Factor de Células Madre/fisiología , Taquicardia/etiología , Triptasas , Factores de Escisión y Poliadenilación de ARNm/genética , Factores de Escisión y Poliadenilación de ARNm/fisiologíaRESUMEN
Mouse red blood cells (RBC) can be fractionated according to their size by counterflow centrifugation. The mean corpuscular hemoglobin content and the enzyme activities (ASAT, LDH, PK and acetylcholinesterase) increase when the mean corpuscular volume (MCV) rises. However, the in-vivo survival of size-separated RBC is similar whatever their MCV is; thus, counterflow centrifugation is not a suitable procedure to achieve an age fractionation of mouse RBC. Moreover, RBC subpopulations collected by counterflow centrifugation are different from those obtained when RBC are fractionated according to their density.
Asunto(s)
Envejecimiento Eritrocítico , Eritrocitos/citología , Animales , Índices de Eritrocitos , Masculino , Ratones , Valores de ReferenciaRESUMEN
To investigate the role of polyclonal stimulation and antigen driven selection in the pathogenesis of acquired immunodeficiency syndrome (AIDS) related lymphomas, we studied the variable region nucleotide sequence of heavy (VH) and light (VL) chains expressed by 3 Burkitt lymphomas (BL) associated with HIV infection. Two cases expressed the VH3-30P1 gene with 88.6% and 86.7% homology when compared to their germinal counterpart, whereas the VH4-18 was rearranged in the third one (89% identity). All these genes displayed high numbers of mutations (27, 22, 28 respectively), predominating in CDR regions. The encoded light chain genes determined for cases 1 and 2 expressed the same V kappa I-018 gene. These results indicate that: 1) Although, it is difficult to address the issue of VH usage based on the limited number of cases studied, Burkitt's lymphoma associated with AIDS may use a restricted repertoire of Ig genes. 2) Mutations and/or replacements predominated in CDR regions, which might suggest the occurrence of an antigen driven selection process, at least in some AIDS associated lymphomas. However, the high ratio of mutations observed in framework (FW) regions also favors the possibility that the antigen selection process is associated with polyclonal B cell stimulation.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/inmunología , Linfoma de Burkitt/inmunología , Genes de Inmunoglobulinas , Región Variable de Inmunoglobulina/genética , Linfoma Relacionado con SIDA/inmunología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Secuencia de Aminoácidos , Secuencia de Bases , Linfoma de Burkitt/complicaciones , Cartilla de ADN/química , ADN Viral/genética , Reordenamiento Génico de Linfocito B , Herpesvirus Humano 4/genética , Humanos , Datos de Secuencia Molecular , Mutación PuntualRESUMEN
INTRODUCTION: Acquired C1 inhibitor deficiency is sometimes associated with lymphoproliferative disorders. EXEGESIS: We report four cases of acquired C1 inhibitor deficiency in association with lymphoproliferative disorders. Three of them were asymptomatic; one was associated with abdominal pain. Four women (median age, 66 years) presented either two non-Hodgkin lymphoma or two chronic lymphocytic leukaemia. C1 inhibitor deficiency was detected fortuitous (n = 1) or during investigation of arthralgia (n = 2), or Gougerot-Sjogren syndrome (n = 1). The deficit was acquired in all cases type I. Auto-immune disorders were associated with: Gougerot-Sjogren syndrome (n = 1), cryoglobulinemia (n = 2), IgM lambda monoclonal gammopathy (n = 1), Coombs positive test (n = 2), IgG anti-cardiolipine antibodies (n = 1). C1 inhibitor deficiency was not modified after lymphoproliferative disorders treatment (radiotherapy, splenic ablation) in two cases but patients were not in complete remission. C1 inhibitor raised normal level in one case, after five chemotherapy regimens, but decreased complement level and C4 split persist. CONCLUSION: Acquired C1 inhibitor deficiency associated with lymphoproliferative disorders is sometimes asymptomatic. Diagnosis could be delay in spite of clinical manifestations. Deficit correction is not constant after lymphoproliferative disorders treatment.
Asunto(s)
Proteínas Inactivadoras del Complemento 1/deficiencia , Leucemia Linfocítica Crónica de Células B/inmunología , Linfoma no Hodgkin/inmunología , Trastornos Linfoproliferativos/inmunología , Anciano , Angioedema/inmunología , Anticuerpos Anticardiolipina/inmunología , Crioglobulinemia/inmunología , Femenino , Humanos , Trastornos Linfoproliferativos/diagnóstico , Persona de Mediana Edad , Síndrome de Sjögren/inmunologíaRESUMEN
BACKGROUND: Pica is an eating disorder characterized by the irrepressible and elective craving for food and non-food substances. Pagophagia is a particular form characterized by an ingestion of ice, often associated with iron deficiency. We report a case of intense and prolonged pagophagia. We also analyse literature about the nature of the link between pica and iron deficiency. CASE REPORT: A forty-two year old woman was admitted for severe anaemia secondary to iron deficiency possibly related to chronic gynaecological bleeding. A diet investigation revealed a pagophagia of about eighty ice cubes per day developing over five years. Iron supplement corrected the anaemia and the pagophagia disappeared in less than fifteen days without recurrence in the following year. CONCLUSION: The disappearance of pagophagia after the correction of iron deficiency supports the theory that pagophagia could well be a symptom of iron deficiency.
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Anemia Ferropénica/complicaciones , Pica/etiología , Adulto , Anemia Ferropénica/terapia , Femenino , Humanos , Hielo , Hierro/uso terapéuticoRESUMEN
OBJECTIVES: To ascertain the attitude of hospital physicians in the Paris area concerning pica and its relation to iron deficiency and to compare findings with data in the literature. METHODS: An anonymous questionnaire was sent to 174 department heads of specialty units caring for iron deficiency patients: internal medicine (n = 56), hepatogastroenterology (n = 39), hematology (n = 13), gynecology and obstetrics (n = 34), pediatrics (n = 32). RESULTS: The overall response rate was 40.2%. Ninety-seven percent of all the physicians found pica in less than 10% of patients with iron deficiency, and 95.6% considered geophagia as the most frequent pica. For 58.5% of the adult medicine practitioners, pica was regarded only as a cause of iron deficiency, but for 64.7% of the pediatricians, pica was both a cause and a symptom of iron deficiency was not sought in a systemic way in 88.6% of the physicians when a cause of iron deficiency was known. CONCLUSION: In the majority of the cases, the attitude of hospital physicians concerning pica is in disagreement with published data, suggesting either epidemiological characteristics specific to the Paris area, or unawareness of the phenomenon.
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Actitud del Personal de Salud , Deficiencias de Hierro , Pica/etiología , Adulto , Encuestas de Atención de la Salud , Médicos Hospitalarios , Humanos , Medicina , Paris , EspecializaciónRESUMEN
INTRODUCTION: Diagnostic features of myelodysplastic syndromes (MDS) are often polymorphic and nonspecific including anemia in most cases. Standard parameters provided by an automated analyzer seldom bring any argument for this diagnosis. The aim of this study was to investigate whether some structural parameters, not routinely provided by Sysmex™ XE 2100 analyzer, could help diagnose MDS in a simple way, adapted to routine practice. METHODS: Blood samples from 184 MDS fully annotated cases and 3545 normal blood count controls were performed with XE 2100 Sysmex™ analyzer. Quantitative and structural parameters were considered. RESULTS: We found that the structural neutrophil parameter, NEUT-X, converted into a semi-quantitative parameter, the granularity index (GI), could be used as a flag for MDS in front of anemia. Negative GI and anemia were able to make otherwise unrecognized MDS stand out in routine practice, increasing the number of slides addressed to review from 67% to 96%, without leading to a large excess of unfounded slide review among non-MDS. CONCLUSION: Including the GI index in the routine parameters provided by the Sysmex analyzer could be of major help for nonspecialized routine laboratories in detecting MDS.
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Síndromes Mielodisplásicos/sangre , Neutrófilos/citología , Autoanálisis , Humanos , Recuento de Leucocitos , Síndromes Mielodisplásicos/diagnósticoRESUMEN
The molecular mechanisms responsible for the evolution from the preleukemic entities of low-risk myelodysplastic syndrome (MDS) to the less favorable forms of high-risk MDS, as well as those enabling transformation to acute myeloid leukemia (AML), are still incompletely understood. Abundant evidence from solid tumors demonstrates that preneoplastic lesions activate signaling pathways of a DNA damage response (DDR), which functions as an 'anticancer barrier' hindering tumorigenesis. Testing the hypothesis that subgroups of MDS and AML differ with respect to DDR, we first assessed markers of DDR (phosphorylation of ATM, Chk-1, Chk-2 and H2AX) in cell lines representing different entities of MDS (P39, MOLM-13) and AML (MV4-11, KG-1) before and after gamma-irradiation. Although gamma-irradiation induced apoptosis and G(2)/M arrest and a concomitant increase in the phosphorylation of ATM, Chk-1 and H2AX in MDS-derived cell lines, this radiation response was attenuated in the AML-derived cell lines. It is noteworthy that KG-1, but not P39 cells exhibit signs of an endogenous activation of the DDR. Similarly, we found that the frequency of P-ATM(+) cells detectable in bone marrow (BM) biopsies increased in samples from patients with AML as compared with high-risk MDS samples and significantly correlated with the percentage of BM blasts. In contrast, the frequency of gamma-H2AX(+) cells was heterogeneous in all subgroups of AML and MDS. Whereas intermediate-1 MDS samples contained as little P-Chk-1 and P-Chk-2 as healthy controls, staining for both checkpoint kinases increased in intermediate-2 and high-risk MDS, yet declined to near-to-background levels in AML samples. Thus the activation of Chk-1 and Chk-2 behaves in accord with the paradigm established for solid tumors, whereas ATM is activated during and beyond transformation. In conclusion, we demonstrate the heterogeneity of the DDR response in MDS and AML and provide evidence for its selective suppression in AML because of the uncoupling between activated ATM and inactive checkpoint kinases.
Asunto(s)
Daño del ADN , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicos/genética , Proteínas de la Ataxia Telangiectasia Mutada , Biopsia , Médula Ósea/patología , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Quinasa de Punto de Control 2 , Daño del ADN/efectos de la radiación , Proteínas de Unión al ADN/metabolismo , Células Precursoras de Granulocitos/efectos de los fármacos , Células Precursoras de Granulocitos/metabolismo , Células Precursoras de Granulocitos/patología , Células Precursoras de Granulocitos/efectos de la radiación , Histonas/metabolismo , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Síndromes Mielodisplásicos/metabolismo , Síndromes Mielodisplásicos/patología , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Fármacos Sensibilizantes a Radiaciones/farmacología , Proteínas Supresoras de Tumor/metabolismoRESUMEN
A series of 38 patients with acute myeloblastic leukemia (AML) with 49 or more chromosomes and without structural abnormalities was selected within the Groupe Francophone de Cytogénétique Hématologique (GFCH) to better define their characteristics. The median age of the patients was 65 years, and all FAB subtypes were represented. Although all chromosomes were gained, some seems to prevail: chromosome 8 (68%), 21 (47%), 19 (37%), and 13 and 14 (34% each). Since MLL rearrangement leads patients in a group with an unfavorable prognosis, search for cryptic rearrangements of MLL was performed in 34 patients and showed abnormalities in 5 (15%). When we applied the most frequent definition of complex karyotypes (three or more abnormalities), all patients with high hyperdiploid AML fall in the unfavorable category. Among the 18 patients without MLL rearrangement receiving an induction therapy, 16 (89%) reached CR and 6 (33%) were still alive after a 31-month median follow-up (14-61 months). Although this study was retrospective, these results suggest that high hyperdiploid AML without chromosome rearrangement seems to be a subgroup of uncommon AML (less than 1%), and may be better classified in the intermediate prognostic group.
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Aberraciones Cromosómicas , Cromosomas Humanos/genética , Leucemia Mieloide/genética , Ploidias , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Reordenamiento Génico , N-Metiltransferasa de Histona-Lisina , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Leucemia Mieloide/tratamiento farmacológico , Leucemia Mieloide/epidemiología , Masculino , Persona de Mediana Edad , Proteína de la Leucemia Mieloide-Linfoide/genética , Pronóstico , Estudios Prospectivos , Estudios RetrospectivosAsunto(s)
Antimetabolitos/uso terapéutico , Azacitidina/uso terapéutico , Cromosomas Humanos Par 5/genética , Cromosomas Humanos Par 7/genética , Monosomía , Síndromes Mielodisplásicos/genética , Deleción Cromosómica , Ensayos de Uso Compasivo , Estudios de Seguimiento , Humanos , Hibridación Fluorescente in Situ , Estimación de Kaplan-Meier , Cariotipificación , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Resultado del TratamientoAsunto(s)
Antineoplásicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Talidomida/análogos & derivados , Acondicionamiento Pretrasplante/métodos , Anciano , Cromosomas Humanos Par 5/genética , Femenino , Eliminación de Gen , Humanos , Lenalidomida , Leucemia Mieloide Aguda/genética , Inducción de Remisión , Talidomida/uso terapéutico , Quimera por Trasplante , Trasplante HomólogoRESUMEN
The classical concept of plasma cell leukaemia (PCL) is reviewed. This disease invariably concerns myeloma, either in its terminal phase (secondary PCL) or particularly rapid and aggressive (primary PCL). A more precise definition of primary PCL would be given by the term leukaemic myelomatosis. Characterization of the membrane antigen CD 56, responsible for the cytoadhesion of malignant plasmocytes in the bone marrow, today offers a convincing pathogenic hypothesis to elucidate this affection which would now appear to be no more than a variant form of myeloma. Acute immunoblastic-plasmoblastic leukaemia and mature cell leukaemic lymphoma would seem to be pathologically related to PCL. Finally, the problems posed by the "enigmatic" plasmacytoid monocyte are discussed.
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Leucemia de Células Plasmáticas/sangre , Mieloma Múltiple/sangre , Antígenos CD/sangre , Antígenos de Neoplasias/sangre , Humanos , Leucemia de Células Plasmáticas/inmunología , Leucemia de Células Plasmáticas/patología , Mieloma Múltiple/inmunologíaRESUMEN
D-dimer assay was performed on 145 cerebrospinal fluid (CSF) samples from patients with or without neoplastic diseases. Levels of D-dimers were significantly higher in carcinoma and lymphoid malignancies with clinical or biological evidence of central nervous system (CNS) involvement than in diseases without such complications. In one patient, serial determinations of D-dimers were well correlated with the appearance and disappearance of CNS involvement. Although this test is not specific for neoplastic affections, our data suggest that the measurement of D-dimers in CSF may be useful in the diagnosis of CNS involvement of neoplastic cells and in monitoring intrathecal therapy in patients with lymphoma, acute lymphoblastic leukaemia or carcinoma. In this study, the D-dimer assay was also positive in some non neoplastic diseases, but failed to differentiate subarachnoid haemorrhage from traumatic lumbar puncture.