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Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory and T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination of anti-Spike specific antibodies. Booster doses increased seroconversion rate and antibody titers in all patient categories, ultimately generating humoral responses similar to those observed in the postinfection cohort. In detail, humoral response with overscale median antibody titers arose in >80% of patients in watch and wait, off-therapy in remission, or under treatment with venetoclax single-agent. Anti-CD20 antibodies and active treatment with BTK inhibitors (BTKi) represent limiting factors of humoral response, still memory mounted in ~40% of cases following booster doses or infection. (Blue) Evaluation of SARS-CoV-2-specific T-cell responses. Number of T-cell functional activation markers documented in each patient. The vast majority of patients, including those seronegative, developed T-cell responses, qualitatively similar between treatment groups or between vaccination alone and infection cases. These data highlight the efficacy of booster doses in eliciting T-cell immunity independently of treatment status and support the use of additional vaccination boosters to stimulate humoral immunity in patients on active CLL-directed treatments.
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COVID-19 , Leucemia Linfocítica Crónica de Células B , Humanos , SARS-CoV-2 , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Vacunas contra la COVID-19 , Anticuerpos , Subunidad alfa del Receptor de Interleucina-2 , Inmunidad Celular , Anticuerpos Antivirales , VacunaciónRESUMEN
AIM: The paper presents the surgical solving of an oesophageal stenosis, using a device of pneumatic dilatation with trans-gastrostomal approach, in a patient with multiple disabling handicaps, secondary severe malnutrition and previously diagnosed with scleroderma. MATERIALS AND METHOD: The patient was admitted with severe cachexia (37 kg, 170 cm), characteristic byzantine face with microstomy, distal phalanges resorption in both superior limbs and complete dysphagia, with limitation of mouth opening.The Barium swallow test revealed distal oesophageal stenosis,with an important dilation of the oesophagus above. RESULTS: A gastrostoma was placed to allow nutrition (Gavriliu procedure), under general anaesthesia with trans-tracheostomal intubation. After 3 years, with her metabolic status improved(59 kg), the patient returned to our clinic asking for a solution for natural feeding. The technical difficulties in solving this case were determined by the limited mouth opening, which made anterograde oro-oesophageal balloon dilatation or bougienage impossible, as well as oro-tracheal intubation.Making use of the presence of the gastrostomal orifice,knowing von Hacker's mechanical dilation procedure and using the metallic Key Med kit with balls offered the possibility of the tactics and strategy of guiding a metallic guidewire introduced via the gastrostoma, then trans-stenotic and pulled out through the oral orifice. A modified Foley catheter (personal procedure) was attached to the initial catheter. The trans-stenotic retrograde traction of the Foley balloon was the pneumatic dilator factor that later allowed easy dilatation with the metallic dilator of the Key Med, to the maximum size. The follow-up showed good results, the patient returned to natural nutrition. CONCLUSIONS: The device of oesophageal pneumatic dilatation allows, using the presented surgical technique, a gentle plasty done under radiological supervision and lowers the frequency of accidents. The dilation permits the following use of Key Med kit. The novelty consists in adapting a well-known technique to a new patented device of pneumatic dilation with bidirectional approach under radiological control, for solving this atypical case.
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Cateterismo/métodos , Estenosis Esofágica/terapia , Gastrostomía , Esclerodermia Sistémica/complicaciones , Adulto , Caquexia/etiología , Cateterismo/instrumentación , Trastornos de Deglución/etiología , Dilatación/métodos , Estenosis Esofágica/complicaciones , Estenosis Esofágica/etiología , Femenino , Humanos , Factores de Riesgo , Resultado del TratamientoRESUMEN
We present the case of a 71-year-old woman diagnosed with chronic lymphocytic leukemia who received multiple chemotherapeutic lines and evolved to acute lymphoblastic leukemia. The patient was Rai stage 0 at the time of the diagnosis and was monitored for almost 9 years. After that, the disease progressed and the patient began chemotherapy (fludarabine/cyclophosphamide combination), obtained complete remission and relapsed one year later after finishing treatment. She received multiple therapeutic regimens, accompanied by multiple infectious complications. After 8 years of evolution since she started chemotherapy, bone marrow aspirate and immunophenotyping revealed acute lymphoblastic leukemia. The occurrence of acute leukemia in CLL is rare and may arise from the same clone; however, most cases appear after patients have received chemotherapy, suggesting that they are therapy-related.
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Antineoplásicos Alquilantes/efectos adversos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Neoplasias Primarias Secundarias , Leucemia-Linfoma Linfoblástico de Células Precursoras/inducido químicamente , Anciano , Resultado Fatal , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/complicacionesRESUMEN
Immunophenotyping of B-cell lymphoproliferative disorders is indispensable, especially in disorders with CD19(+) CD5(+) B lymphocytes, where we have to make the distinction between low grade neoplasia, such as chronic lymphocytic leukemia with CD23(+) malignant lymphocytes, and aggressive neoplasia such as mantle cell lymphoma with CD23(-) malignant lymphocytes. We found some cases of CD19(+) CD5(+) lymphoproliferative disorders that do not meet all criteria for diagnosis of chronic lymphocytic leukemia or mantle cell lymphoma. For instance, we found cases with a low or no expression of CD23, asociated with absence of expression of FMC7 and surface immunoglobulins. These cases could be classified as "borderline" CD19(+) CD5(+) B cell lymphoproliferative disorders, with an intermediate neoplasic grade.
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UNLABELLED: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders; they are characterized by ineffective hematopoiesis and a predilection to the development of acute myeloid leukemia (AML). For a rapid evaluation of the outcome in myelodysplastic patients non-cytogenetic prognostic scores can be used. AIM: This study proposed to demonstrate that age and gender are important factors in the outcome of the patients diagnosed with myelodysplastic syndrome. MATERIALS AND METHODS: This study was conducted in the Department of Hematology of the Emergency University Hospital Bucharest during October 2008 and October 2012. RESULTS: Male sex and age higher than 60 years are associated with high risk in the studied cases by using the Spanish prognostic score. According to Goasguen score: male sex and age, patients older than 60 years, present characteristics associated with an intermediate risk. Based on the Dusseldorf score, age over 60 years and female gender were associated with pronounced risk in the examined group. By examining the Bournemouth score in our group, we found that age > 60 years correlated with a higher frequency of risk, but no significant differences regarding the sex of patients were observed. CONCLUSIONS: We concluded that age > 60 years and male gender are important predisposing factors in the survival.
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Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/epidemiología , Síndromes Mielodisplásicos/fisiopatología , Proyectos de Investigación , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Medición de Riesgo , Factores de Riesgo , Rumanía/epidemiología , Factores SexualesRESUMEN
We present the case of a patient who presented cells with different morphologic appearance, lymphoblasts on peripheral blood smear, lymphoblasts on bone marrow aspirate and myloblasts on bone marrow biopsy, and immunophenotyping, leading to different stage diagnosis. The final diagnosis was that of acute myeloid leukemia (LAM0).
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Leucemia Mieloide Aguda/diagnóstico , Adulto , Médula Ósea/patología , Humanos , Leucocitos/patologíaRESUMEN
Leptomeningeal carcinomatosis, also known as carcinomatous meningitis, is defined by spreading of neoplastic cells to the meninges and ventricles, and is a form of cancer dissemination. In this case, a patient with inflammatory bowel disease had developed a neoplastic process that spread to the meninges. A 49-year-old woman developed an abdominal pain, and was diagnosed the same month with Crohn's disease, complicated with intestinal perforation, for which she was hospitalized. Pathological examination revealed acute phase-terminal ileitis. She undergone many hospitalizations during which she was suspected to have celiac disease, inflammatory bowel disease, and tuberculous meningitis, as well as femoral head necrosis after she had been unsuccessfully treated with Prednisone for Crohn's disease. After she developed peripheral bilateral facial paresis, bilateral hypoacusia, hypotonia, tetraparesis and diminished osteotendinous reflexes at the legs, the patient was admitted in our department. Several lumbar punctures were performed but no specific disease could be detected. The MRI performed showed pachymeningeal and leptomeningeal inflammation. Tuberculous meningitis was taken into consideration and the patient was transferred into an Infectious Disease Department where this diagnostic was infirmed. The patient was retransferred into the Department of Neurology where after an episode of hematemesis she had a cardiac arrest and deceased. Inflammatory bowel disease may involve different segments of the intestine, and may be accompanied by a variety of conditions, such as neurologic findings, osteoarticular manifestations and also may be the starting point of a neoplastic process. The patient had an inflammatory bowel condition, which by the time it was appropriately diagnosed as being Crohn's disease, a neoplastic process spread to the meninges, causing multiple cranial nerve palsy, tetraparesis, along other neurological manifestations.
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Enfermedad de Crohn/complicaciones , Carcinomatosis Meníngea/complicaciones , Enfermedad de Crohn/patología , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética , Carcinomatosis Meníngea/patología , Persona de Mediana Edad , Polineuropatía Paraneoplásica/complicacionesRESUMEN
Chronic myeloid leukemia (CML) represents about 15% of all leukemia cases. Although the incidence of the disease is rather low, the therapeutic progress of the last decade has dramatically changed the evolution of this disease, whose survival considerably increased and in whom we now speak even about cure. The success of the therapy is strongly connected to the precocity of the diagnosis and molecular targeted therapy that implies a close monitoring of the patient. The specific molecular assay, that developed a lot in the last years, became an important tool in the management of these patients, providing the possibility of efficient changing in therapy. The purpose of our study was to identify the characteristics of our CML patients in terms of clinical and biological behavior. We analyzed 21 patients diagnosed between October 2007 and December 2010 and compared the data with a historical group of patients, also diagnosed in our department between March 2005 and September 2007. We found a better outcome and overall survival in the study group, due to improved diagnosis and monitoring techniques as well as to better access to therapy.
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Benzamidas/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Adulto , Anciano , Análisis Citogenético , Femenino , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Hepatitis B and C viruses' infections are often associated with hematological disorders in evolution, suggesting that these viruses have a tropism for peripheral blood and/or bone marrow cells. AIM: To analyze the hematological parameters and bone marrow findings in a group of patients diagnosed with chronic lymphoproliferative disorders (CLD) and hepatitis viruses B, C, D infections, which were included in the research grant (acronym LIMFO-VIR) between December 2007 and May 2010 in the Hematology Department of the Emergency University Hospital of Bucharest. METHODS AND RESULTS: Patients were diagnosed by using immunopathology according to the WHO criteria. The analyzed group included 42 patients (both sexes), with the mean age of 60,35 years. The most frequent hematologic disease was non-Hodgkin's lymphoma 30/42 (71,42%), followed by chronic lymphocytic leukemia (16,66%) and Hodgkin's lymphoma (7,14%). Hepatitis viruses were distributed: 17/42 (40,47%) patients with HBV, 22/42 (52,38%) with HCV and 3/42 (7,14%) had a double/triple association of viruses. Most of the patients had an indolent type of disease - 27/42 (64,28%), whereas 15/42 (35,71%) had an aggressive one, pattern found both in the HBV and HCV infected groups. An abnormal bone marrow result was revealed in 32/42 (76,19%) patients, 19 (59,37%) of them being HCV infected. Myelodysplasia was found in 6/42(14,28%) patients, the majority being HCV infected, all having an indolent form of CLD. The antiviral therapy did not influence the hematological parameters (no significant differences were found between the groups with/without an antiviral therapy). DISCUSSIONS: Patients with hepatitis virus infections may associate neutropenia and thrombocytopenia; the mechanisms are thought to involve hypersplenism, autoimmune processes and antiviral therapy. We excluded the influence of chemotherapy, as the study was performed before the treatment. In our group, patients whether HBV or HCV infected, presented an isolated cytopenia. The abnormal bone marrow cellularity (increased or decreased) and dysplasia were found especially in the HCV group. There are studies showing no association between myelodysplasia and hepatitis viruses; others found a strong relation of these. One of the mechanisms of myelodysplasia could be a dysregulation of the immune system. Conclusions. Bone marrow/peripheral blood features correlate with the type of viral infection and HCV is more prone to develop additional hematological changes than HBV. The degree of bone marrow involvement by CLDs influences these features. We considered mandatory to perform a bone marrow analysis at the diagnosis of CLDs to stage and to establish if other bone marrow changes were present, a crucial aspect for therapy and outcome of the disease. The association between the hepatitis viruses - myelodysplasia- autoimmunity seems to have a role in the lymphoproliferative disorders etiology. ABBREVIATIONS: CLD - chronic lymphoproliferative disorders; NHL- non-Hodgkin's lymphoma, CLL- chronic lymphocytic leukemia, HL- Hodgkin's lymphoma, MDS - myelodysplastic syndrome, AML - acute myeloid leukemia.
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Médula Ósea/metabolismo , Virus de Hepatitis/patogenicidad , Trastornos Linfoproliferativos/sangre , Trastornos Linfoproliferativos/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/virología , Femenino , Hepatitis Viral Humana/complicaciones , Hepatitis Viral Humana/diagnóstico , Humanos , Trastornos Linfoproliferativos/virología , Masculino , Persona de Mediana EdadRESUMEN
Imatinib mesilate (IM) is the first line therapy for chronic myeloid leukemia (CML) patients in chronic phase. Although it offers a complete cytogenetic response (CCyR) in a majority of patients, there still are some rare cases in which a sudden blast crisis (SBC) evolves. The mechanism of this unexpected event is not yet completely understood. We present the case of a female patient who developed a SBC while being under IM therapy. We do not know for sure which is the role of IM in this event, but current available data suggest that this drug may have a permissive effect on the evolution of some aggressive subclones in the context of restored normal cell population.
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Crisis Blástica , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Benzamidas , Femenino , Humanos , Mesilato de Imatinib , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
We present the case of a 53 years old woman diagnosed with splenic marginal zone lymphomas with plasmacytic differentiation (after a lymph node biopsy), who, complained of mild asthenia, weight loss (about 10 kg in 9 months), spatial disorientation during the last period. The clinical examination revealed slight pallor, normal cardiovascular and respiratory examination; painful cervical, about 5cm in diameter and also non-painful inguinal lymphadenopathies, increased consistency, freely movable, about 2 cm in diameter. The patient presented enlarged liver (lower limit at 3 cm below the ribs) and spleen (inferior pole at the ombilicus). The laboratory tests showed leucocytosis with lymphocytosis-a clonal population of lymphocytes- CD19+, CD20low+, CD22+, CD5low+, CD24+, CD200low+, CD79B+, CD43-, FMC7+/-, CD10+/-, CD34-, BCL2+, TdT-, CD34-, CD10-, CD3-. We suggested the diagnosis of mantle cell lymphoma, blastoid variant and performed a bone marrow biopsy . The bone marrow biopsy excluded the diagnosis of mantel cell lymphoma, based on the absence of cycline D1. The histopathological appearance and the immunohistochemical tests (CD20+, CD79a+, CD5low+, TdT-, CD34-cycline D1-) suggested a blastoid variant of small lymphocytic lymphoma.
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Leucemia Linfocítica Crónica de Células B/diagnóstico , Médula Ósea/patología , Diagnóstico Diferencial , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Leucemia Linfocítica Crónica de Células B/clasificación , Linfoma de Células B de la Zona Marginal/diagnóstico , Persona de Mediana EdadRESUMEN
Background: The diagnosis and management of the patients with chronic lymphoproliferative diseases have become dependent on immunological criteria. Flow cytometry immunophenotyping is used for rapid and specific diagnosis but there are cases when we are not facing a typical immunophenotype, so there is a constant need to find new markers and new combinations of markers that would allow the improvement and the development of our diagnosis. Aim: Our aim was to evaluate CD 200 expression in different B-cell chronic lymphoproliferative disorders. CD200 is a membrane glycoprotein belonging to the immunoglobulin superfamily and the over-expression of CD200 has been reported in a number of malignancies, including CLL, as well as on cancer stem cells. Methods: We analyzed the CD200 expression in 122 patients diagnosed with chronic lymphoproliferative disorders (100 patients with CLL, 10 patients with splenic marginal zone lymphoma (SMZL), 10 patients with MCL and 2 patients with hairy cell leukemia), in the Department of Hematology of the University Emergency Hospital, Bucharest. We performed immunophenotypical analysis of peripheral blood and bone marrow aspiration on BD FACS Calibur flowcytometer. Results: CD200 was brightly expressed in all 100 CLL patients (100%). In SMZL patients, CD200 was dim positive (40%-60%), in patients with HCL. CD200 was also bright positive (96% and 97%) and in patients with MCL CD200 was negative (1-10%); CD 200 was significantly higher in CLL patients compared with other B-cell chronic lymphoproliferative disorders. We found 14 patients with CD19, CD5 positive population and CD23- , but with high expression of CD 200. Cyclin D1 was negative on bone marrow biopsy in 13/14 of these patients. (1/14 patients were without bone marrow involvement); Conclusions: CD200 has a great impact in diagnosing B- chronic lymphoproliferative disorders, especially when we want to determine the origin of a CD19, CD5 positive population and distinguish between CLL and MCL. CD 23 is a reliable marker in those cases, but, as we showed, CD23 might have a lower specificity than CD200 for CLL. We added CD200 in our panels in order to diagnose chronic lymphoproliferative disorders, not to replace CD 23, but to improve and save time in our diagnostic process. The high expression of CD200 in CLL and HCL could open the option for new- targeted therapy (anti-CD200).
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The hemorrhagic and thrombotic diathesis represents a frequent complication in myelodysplastic syndromes (MDS) and in acute leukemias. They are correlated with the number of the platelets, but also with their qualitative disorders, such as membrane glycoprotein changes. The latter are revealed by many platelet studies including flow-cytometry and comprise modified activation, secretion and aggregation patterns.
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Trastornos de las Plaquetas Sanguíneas , Plaquetas , Leucemia/complicaciones , Síndromes Mielodisplásicos/complicaciones , Enfermedad Aguda , Trastornos de las Plaquetas Sanguíneas/sangre , Trastornos de las Plaquetas Sanguíneas/etiología , Trastornos de las Plaquetas Sanguíneas/patología , Plaquetas/metabolismo , Plaquetas/patología , Citometría de Flujo , Humanos , Leucemia/sangre , Síndromes Mielodisplásicos/sangre , Agregación Plaquetaria , Recuento de Plaquetas , Pruebas de Función Plaquetaria , Glicoproteínas de Membrana Plaquetaria/clasificación , Glicoproteínas de Membrana Plaquetaria/metabolismoRESUMEN
BACKGROUND: Patients with Myeloproliferative Neoplasms-(MPN) have a high risk of thrombotic complications. Portal vein thrombosis is a severe complication, which in many cases, appears at the onset of the disease; the risk factors are related to the presence of qualitatively altered thrombocytes and leucocytes, leading to their activation and appearance of leukocytes-platelet-aggregates; anomalies of portal vein endothelial cells are also implicated. The presence of JAK2V617F mutation increases the risk for splahnic thrombosis. METHODS AND RESULTS: We present three patients with portal vein thrombosis and Budd Chiari syndrome, who were further diagnosed with MPN-the thrombosis was the onset event of the disease. CONCLUSION: Patients were diagnosed with thrombosis of the portal vein before being diagnosed with MPN. Splenectomy was not associated with risk of thrombosis for the two cases in which it was performed; for one case, splenectomy was a therapeutic method to resolve portal hypertension. All patients had homozygous JAK2 mutation, which is associated in recent studies with increased risk of portal, mesenteric thrombosis. The high number of platelet was difficult to control for all patients. Bone marrow biopsy and determination of JAK status are valuable investigations for patients who have splenoportal thrombosis, with no apparent identifiable cause.
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Síndrome de Budd-Chiari/etiología , Trastornos Mieloproliferativos/complicaciones , Vena Porta , Adulto , Humanos , Janus Quinasa 2/genética , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/genéticaRESUMEN
Chronic myeloproliferative disorders (CMD) and Myelodisplastic Syndromes (MDS) represents a group of clonal pluripotent stem-cell pathologies. During their natural history, the clinical picture reveals both thrombosis and hemorrhage. The thrombosis could affect the microvessels, and also the large vessels, including even less usual territories (suprahepatic veins, porta vein, pulmonary vein). There are many factors contributing to thrombosis in myeloproliferative chronic disorders--the associated comorbidities, the numeric alterations of blood elements and also the disorders of the platelet's function. Thus, there were described quantitative and qualitative anomalies of platelet's receptors: GP Ib, GP IIb/IIIa, GP IV, GP VI, thrombopoietin receptor of the platelet cMPL, the increase of platelet activation; the increase of P selectin and thrombospondin and the increase on GP IIb/IIIa expression--they were all correlated with thrombosis. An important role has been attributed to JAK2 mutation, which affects the platelet receptor for thrombopoietin cMPL. Regarding the hemorrhage in chronic myeloproliferative syndrome, it is favored by many disorders in platelet's function, such as: the decrease of von Willebrand factor's receptor of the platelet, which leads to acquired Bernard Soulier syndrome; quantitative and qualitative disorders of dense granules of the platelet, decrease of the secretion and platelet aggregation after epinephrine, ADP and collagen stimulation. It was also described the acquired von Willebrand syndrome, most frequently type 2.
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Trastornos de las Plaquetas Sanguíneas/complicaciones , Plaquetas/metabolismo , Síndromes Mielodisplásicos/complicaciones , Trastornos Mieloproliferativos/complicaciones , Síndrome de Bernard-Soulier/etiología , Trastornos de las Plaquetas Sanguíneas/sangre , Trastornos de las Plaquetas Sanguíneas/fisiopatología , Antígenos CD36/sangre , Hemorragia/etiología , Humanos , Interleucinas/sangre , Janus Quinasa 2/sangre , Mutación , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/fisiopatología , Trastornos Mieloproliferativos/sangre , Trastornos Mieloproliferativos/fisiopatología , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Trombosis/etiología , Enfermedades de von Willebrand/etiologíaRESUMEN
We present the case of a patient with a double transformation during the evolution of chronic hematopoietic malignancy - JAK2 positive chronic myeloproliferative neoplasm; the first transformation had occurred previous to the presentation in our Department, but the second transformation was observed in evolution and it was into a rapidly evolving disease, followed by survival of less than one month. We underline the very poor prognosis -- overall survival of 2.5 years from initial presentation -- a much reduced survival for a chronic myeloproliferative neoplasm, probably due also to multiple associated pathology. Also, the other interesting element of the case is related to the dysfunctional platelets -- hemorrhagic complication at increased platelet count, respectively thrombosis at platelet count under 20000/mmc.
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Transformación Celular Neoplásica , Leucemia Mieloide Aguda/diagnóstico , Policitemia Vera/diagnóstico , Mielofibrosis Primaria/diagnóstico , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Biomarcadores/sangre , Enfermedad Crónica , Resultado Fatal , Humanos , Janus Quinasa 2/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/enzimología , Leucemia Mieloide Aguda/genética , Masculino , Mutación , Recuento de Plaquetas , Policitemia Vera/tratamiento farmacológico , Policitemia Vera/enzimología , Policitemia Vera/genética , Mielofibrosis Primaria/tratamiento farmacológico , Mielofibrosis Primaria/enzimología , Mielofibrosis Primaria/genética , Pronóstico , Embolia Pulmonar/diagnóstico , Factores de Riesgo , Esplenomegalia , Trombocitosis/diagnóstico , Tromboembolia Venosa/diagnósticoRESUMEN
BACKGROUND: Chronic lymphoproliferative disorders (CLD) are frequently found in patients with hepatitis viral infections, which can lead to changes in pathogenesis. Hepatitis viruses are hepatotrope viruses, potentially lymphotrope and also potentially oncogenic (hepatocellular carcinoma) viruses. HBV and HCV are involved in autoimmune disorders and in the ethiopathogeny of chronic lymphoproliferative disorders. AIM: Detection of immunophenotype changes of malignant lymphocytes in CLD--especially CLL--associated with hepatitis viral infections. MATERIALS AND METHODS: Bone marrow aspirate, peripheral blood samples on EDTA were available for analysis from 58 patients from a follow-up schedule of the Department of Hematology SUUB from March 2008 until June 2009. The patients were diagnosed with chronic lymphoproliferative disorders associated with hepatitis virus B/C/D infections. A group of 28 consecutive unselected patients with CLL who met the diagnostic criteria of the National Cancer Institute-Working Group (NCI NCIWG), and associated hepatitis viral infection (v-CLL) were studied for the expression of several immunophenotypical markers, in comparison to CLL patients without viral infection (control group). Immunophenotyping analysis was performed on a FACS Calibur flowcytometer with a large panel according to EGIL/WHO recommendations. The diagnosis was completed after the histological and immunochemical analysis from tumoral lesions. RESULTS: Demographics characteristics--male/female ratio 1/2, average age 64 years. Disease type: 90% B-CLD, 5% T-CLD, 5% Hodgkin's disease. The viral infections: 58.53% HCV, 34.41% HBV, 2.43% HBV+HDV, 2.43% HCV+HDV, 2.43% HBV+HCV+HDV. We found in CLL with viral coinfection (v-CLL) cases an elevated expression of B-cell markers--CD19 (Md95/92), CD20 (Md 90/39), CD79b (Md58/31), CD23 (Md67/37). Poor prognosis markers have a higher expression in v-CLL: CD38 (Md49/24), Bcl2 (Md 46/5), cyclin D19 (Md 11/0.5). No change in ZAP-70 expression was observed: Md 59.5/59.1. DISCUSSIONS: Hepatitis viruses could be involved in the pathogenesis of CLD, but as a trigger for a more aggressive outcome. Higher expression of B-cell markers CD19, CD20 in CLL with viral infection suggests a change to atypical CLL, sustained by elevated expression of known poor prognosis markers bcl-2, cyclin D1 and CD38. Lack of ZAP-70 expression could be explained by a strong correlation with a basic unmutated IgVH status, not related to the viral infection. We found a higher frequency of HCV infection in patients with CLD and especially in CLL patients, which were analyzed extensively for immunophenotypical changes. In the present study, we demonstrated that this CD5+ B cell population with clonal expansion, defining CLL patients, has a different immunophenotype, probably related to the hepatitis viral infection.
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Hepatitis/complicaciones , Hepatitis/inmunología , Inmunofenotipificación , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/inmunología , Linfocitos/inmunología , Antígenos de Neoplasias/inmunología , Biomarcadores de Tumor/inmunología , Femenino , Hepatitis/epidemiología , Hepatitis/virología , Humanos , Incidencia , Leucemia Linfocítica Crónica de Células B/epidemiología , Leucemia Linfocítica Crónica de Células B/virología , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
The European LeukemiaNet (ELN), workpackage 10 (WP10) was designed to deal with diagnosis matters using morphology and immunophenotyping. This group aimed at establishing a consensus on the required reagents for proper immunophenotyping of acute leukemia and lymphoproliferative disorders. Animated discussions within WP10, together with the application of the Delphi method of proposals circulation, quickly led to post-consensual immunophenotyping panels for disorders on the ELN website. In this report, we established a comprehensive description of these panels, both mandatory and complementary, for both types of clinical conditions. The reason for using each marker, sustained by relevant literature information, is provided in detail. With the constant development of immunophenotyping techniques in flow cytometry and related software, this work aims at providing useful guidelines to perform the most pertinent exploration at diagnosis and for follow-up, with the best cost benefit in diseases, the treatment of which has a strong impact on health systems.
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Leucemia/diagnóstico , Trastornos Linfoproliferativos/diagnóstico , Enfermedad Aguda , Humanos , Inmunofenotipificación , Leucemia/inmunología , Trastornos Linfoproliferativos/inmunologíaRESUMEN
Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder in which the diagnosis is confirmed by detection of a genetic marker: Philadelphia (Ph) chromosome in almost 90% of cases. Some of Ph1 negative patients, nevertheless, test positive for the abnormal gene, or the abnormal protein associated with this chromosome, when more sensitive studies, such as PCR or FISH are used and nowadays the diagnosis of CML is based, not only on cytogenetic, but also on molecular analysis. The better understanding of the CML biology provided by the latest researches requires a deeper knowledge about the epidemiologic data in each geographic area, so the compiling of a National and/or European Registry for CML patients, that represents one of the aims of this study, became a stringent matter in our days; it can offer valuable data concerning the real incidence of this disease in Romania and can provide the basics for establishing long-term budgetary strategies.