RESUMEN
We search for the presence of somatic mutations in 12 genes related to MDS, MPN, and AML in a Brazilian cohort composed of 609 elderly individuals from a census-based sample.
Asunto(s)
Leucemia Mieloide/genética , Neoplasias/genética , Factores de Edad , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Estudios de Cohortes , Femenino , Hematopoyesis , Humanos , Leucemia Mieloide/sangre , Leucemia Mieloide/epidemiología , Masculino , Persona de Mediana Edad , Mutación , Neoplasias/sangre , Neoplasias/epidemiología , Secuenciación del Exoma/métodosRESUMEN
CONTEXT: The prognosis of severe aplastic anemia has improved since the introduction of bone marrow transplantation and treatment with antithymocyte globulin. In contrast to the success of these protocols, studies with long term follow-up have shown the occurrence of clonal diseases such as paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome and acute leukemia in aplastic anemia. CASE REPORT: We report the first case of a Brazilian patient with aplastic anemia who developed myelodysplastic syndrome and acute myeloid leukemia showing acquired hemoglobin H and increased fetal hemoglobin.
Asunto(s)
Anemia Aplásica/complicaciones , Hemoglobina H , Leucemia Mieloide/etiología , Enfermedad Aguda , Adulto , Anemia Aplásica/sangre , Resultado Fatal , Humanos , Leucemia Mieloide/sangre , Masculino , Síndromes Mielodisplásicos/complicaciones , Factores de TiempoRESUMEN
Using a non-myeloablative, immunosuppressive, fludarabine-based conditioning regimen, we performed allogeneic peripheral blood stem cell transplants totally on an outpatient basis in four patients (two with chronic myelogenous leukemia, one with acute myelogenous leukemia and one with thalassemia major). The median granulocyte recovery time to 0.5 x 109/l was 10 days and the lowest absolute neutrophil count was 0.064 x 109/l; only one patient developed thrombocytopenia below 20 x 109/l. No patient required red blood cell transfusions and one was given a single prophylactic platelet transfusion. All patients are alive at 210-390 (median 285) days and have definite evidence of chimerism; one developed biopsy-proven GVHD on day 50, with a limited cutaneous rash. The procedure is less costly than its counterpart using myeloablative conditioning regimens and may represent another approach in the management of patients requiring an allogeneic stem cell transplant. Bone Marrow Transplantation (2000) 25, 131-133.
Asunto(s)
Atención Ambulatoria , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide/terapia , Acondicionamiento Pretrasplante/métodos , Talasemia beta/terapia , Adolescente , Adulto , Atención Ambulatoria/economía , Transfusión de Componentes Sanguíneos , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/economía , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Leucemia Mieloide/sangre , Leucemia Mieloide/complicaciones , Recuento de Leucocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Tasa de Supervivencia , Trombocitopenia/etiología , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/economía , Resultado del Tratamiento , Vidarabina/efectos adversos , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico , Talasemia beta/sangre , Talasemia beta/complicacionesRESUMEN
BACKGROUND: A recent update of FAB classification has included a myeloid leukemia subtype with a minimal degree of differentiation, that has been denominated LMA-MO. AIM: To report the clinical, morphological and immunophenotypic features of patients with LMA-MO. PATIENTS AND METHODS: Eight patients, out of 368, with acute myeloid leukemia that were studied in the Hematology Laboratory of a public hospital in Santiago, were classified as LMA-MO. RESULTS: Blast cell morphology was undifferentiated or of subtype FAB-L2 lymphoblastic leukemia with medium sized blasts, agranular basophilic cytoplasm, reticular nuclear chromatin and a prominent nucleolus. Cytochemical staining was negative for peroxidase and esterases, immunophenotyping showed the expression of one or more myeloid antigens (CD13, CD33) and was negative for lymphoid antigens. Immunocytochemical expression of myeloperoxidase was positive in the three cases where it was performed. Only one patient achieved complete remission and is free of disease after 36 months of follow up. All other patients died without obtaining remission, six shortly after the onset and one 12 months after. CONCLUSIONS: The diagnosis of LMA-MO is essential considering its dismal prognosis.
Asunto(s)
Leucemia Mieloide/diagnóstico , Enfermedad Aguda , Anciano , Médula Ósea/patología , Femenino , Humanos , Inmunofenotipificación , Lactante , Recién Nacido , Leucemia Mieloide/sangre , Masculino , Persona de Mediana EdadRESUMEN
Low-density lipoprotein (LDL) could be used as a carrier of chemotherapeutic agents to neoplastic cells that overexpress LDL receptors (rLDL), but LDL is difficult to obtain and handle. Recently, it was observed that a protein-free emulsion resembling the lipid portion of LDL (LDE) behave like native LDL when injected into the bloodstream. In this study, the evidence that LDE is taken up by rLDL was expanded by comparing LDL and LDE plasma decay curves in rabbits and by competition experiments with lymphocytes. To verify whether LDE could be removed from the plasma by neoplastic cells with increased rLDL, LDE labeled with 14Ccholesteryl ester was injected into 14 patients with acute myeloid leukemia (AML) and into 7 with acute lymphocytic leukemia (ALL). In AML rLDL expression is increased but in ALL it is normal. LDE plasma fractional clearance rate (FCR, in h-1) was calculated from the remaining radioactivity measured in plasma samples collected during 24 h following injection. LDE FCR was 3-fold greater in AML than in ALL patients 0.192 +/- 0.210 (SD) and 0.066 +/- 0.033 h-1, respectively, P < 0.035. When LDE injection was repeated in 9 AML patients in hematological remission, LDE FCR diminished 66% compared to the pretreatment values (from 0.192 +/- 0.210 to 0.065 +/- 0.038 h-1, P < 0.02), so that it could be estimated that nearly 66% of the emulsion was taken up by AML cells and only 34% by the normal tissues. As expected, LDE FCR was unchanged in 4 patients with ALL in hematological remission (0.069 +/- 0.044 h-1). Gamma camera images obtained 6 h after the injection of 99mTc-label LDE into one patient with ALL showed biodistribution similar to that of LDL. In one AML patient LDE was comparatively more concentrated over the areas corresponding to the bone marrow infiltrated by AML cells. Our results indicate that LDE FCR is increased in a disease known to contain malignant cells that overexpress rLDL, suggesting that LDE is taken up by malignant cells with increased rLDL.
Asunto(s)
Emulsiones/farmacocinética , Leucemia Mieloide/metabolismo , Lipoproteínas LDL/farmacocinética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Enfermedad Aguda , Adolescente , Adulto , Animales , Unión Competitiva , Niño , Portadores de Fármacos/farmacocinética , Femenino , Humanos , Leucemia Mieloide/sangre , Leucemia Mieloide/diagnóstico por imagen , Linfocitos/metabolismo , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico por imagen , Conejos , Cintigrafía , Tecnecio/metabolismoRESUMEN
A 125I-labeled 120-kDa fibronectin fragment (FN120) containing the RGD binding site was employed to assess FN120 receptor levels in control and dimethylsulfoxide (DMSO)-differentiated HL60 cells, as well as in leukemic peripheral and bone marrow blast cells from acute lymphoid (ALL) and myeloid (AML) patients. Fibronectin CS1 fragment receptor alpha 4 (VLA4-alpha) and RGD-dependent alpha 5 integrin subunits (VLA5-alpha) were characterized by specific monoclonal antibodies (MoAb). HL60 cells, induced along the granulocytic pathway with DMSO, displayed low FN120 binding level densities (36,070 +/- 5142 sites/cell (s/c) vs. 19,780 +/- 4564 s/c, P < 0.005), respectively, for untreated and treated cells) together with decreased VLA5-alpha expression. Granulocytes displayed low levels of FN120 receptors (3167 +/- 1165 s/c) with weak VLA5-alpha expression and absence of VLA4-alpha. Normal lymphocytes displayed 17,670 +/- 8,705 s/c FN120 receptors and VLA4-alpha and VLA5-alpha. The mean FN120 binding levels and mean VLA5-alpha expression were lower in peripheral blast cells, both in ALL and AML, than in the bone marrow leukemic cells. VLA4-alpha remained the same irrespective of cell localization. FN120 binding sites and differential expression of VLA4-alpha and VLA5-alpha integrin molecules on hemopoietic cells could be related to lineage characteristics or cell type distribution within hemopoietic tissue.
Asunto(s)
Médula Ósea/patología , Leucemia Mieloide/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Receptores de Fibronectina/biosíntesis , Adolescente , Secuencia de Aminoácidos , Diferenciación Celular/fisiología , Niño , Preescolar , Humanos , Lactante , Datos de Secuencia MolecularRESUMEN
A microemulsion of lipid composition resembling low-density lipoprotein (LDL), but devoid of apolipoproteins and labeled with [14C]-cholesteryl oleate was injected into 16 healthy subjects and into 15 patients with acute myeloid leukemia (AML). Removal from plasma of the lipid label was higher in the leukemic group compared to healthy subjects in terms of fractional clearance rate (0.185 +/- 0.205 and 0.080 +/- 0.030 h-1, respectively, P < 0.03). When the emulsion was again injected into 10 of the AML patients after complete hematological remission, the fractional clearance rate of cholesteryl ester was reduced to one third of the value observed prior to treatment (0.061 +/- 0.038 h-1) and was not different from that obtained for the healthy subjects. Also, in untreated AML patients, serum LDL-cholesterol levels inversely correlated with the values of fractional clearance rate of the microemulsion. This correlation was no longer observed after treatment. These data suggest that the LDL-like microemulsion was selectively taken up by the neoplastic cells presumably by interaction with LDL receptors. Therefore, microemulsions may function as potential carriers for anticancer drugs that are targeted to tumor cells for patients with acute myeloid leukemia. Unlike native LDL, microemulsions are suitable for utilization in routine clinical practice.
Asunto(s)
Emulsiones Grasas Intravenosas/uso terapéutico , Leucemia Mieloide/sangre , Lípidos/sangre , Lipoproteínas LDL/sangre , Enfermedad Aguda , Radioisótopos de Carbono , Ésteres del Colesterol , Evaluación de Medicamentos , Emulsiones Grasas Intravenosas/farmacocinética , Femenino , Humanos , Leucemia Mieloide/tratamiento farmacológico , Lipoproteínas LDL/efectos de los fármacos , Masculino , Tasa de Depuración Metabólica , Factores de Tiempo , Triglicéridos/sangreRESUMEN
A microemulsion of lipid composition resembling low-density lipoprotein (LDL), but devoid of apolipoproteins and labeled with [14C]-cholesteryl oleate was injected into 16 healthy subjects and into 15 patients with acute myeloid leukemia (AML). Removal from plasma of the lipid label was higher in the leukemic group compared to healthy subjects in terms of fractional clearance rate (0.185 +/- 0.205 and 0.080 +/- 0.030 h-1, respectively, P < 0.03). When the emulsion was again injected into 10 of the AML patients after complete hematological remission, the fractional clearance rate of cholesteryl ester was reduced to one third of the value observed prior to treatment (0.061 +/- 0.038 h-1) and was not different from that obtained for the healthy subjects. Also, in untreated AML patients, serum LDL-cholesterol levels inversely correlated with the values of fractional clearance rate of the microemulsion. This correlation was no longer observed after treatment. These data suggest that the LDL-like microemulsion was selectively taken up by the neoplastic cells presumably by interaction with LDL receptors. Therefore, microemulsions may function as potential carriers for anticancer drugs that are targeted to tumor cells for patients with acute myeloid leukemia. Unlike native LDL, microemulsions are suitable for utilization in routine clinical practice
Asunto(s)
Humanos , Masculino , Femenino , Emulsiones Grasas Intravenosas/uso terapéutico , Leucemia Mieloide/sangre , Lípidos/sangre , Lipoproteínas LDL/sangre , Enfermedad Aguda , Radioisótopos de Carbono , Ésteres del Colesterol , Evaluación de Medicamentos , Emulsiones Grasas Intravenosas/farmacocinética , Leucemia Mieloide/tratamiento farmacológico , Lipoproteínas LDL/efectos de los fármacos , Tasa de Depuración Metabólica , Factores de Tiempo , Triglicéridos/sangreRESUMEN
Several platelet function abnormalities have been described in the myeloproliferative syndromes. We have measured the intraplatelet vWF:Ag and fibrinogen (FI) in the platelet lysates by Laurell technique in 11 patients with polycythemia vera (PV), 10 with essential thrombocythemia (ET), 14 with chronic myelocytic leukaemia (CML) and 3 with myelofibrosis (MF) and these results were correlated with platelet function abnormalities. Decreased intraplatelet levels of vWF:Ag and FI were found in all the patients with ET and MF, in 8 out of 11 PV and 3 out of 14 CML. A statistical significant correlation was observed between the intraplatelet levels of vWF:Ag and FI in the control group and in CML and PV, but no correlation was found in ET and MF. No correlation was observed between the plasmatic and the intraplatelet levels of vWF:Ag and FI in any group. Evidences of platelet activation (spontaneous platelet aggregation or circulating platelet aggregates) were observed in 40% of the cases with ET and PV, and all these cases had low intraplatelet levels of both antigens. None of the cases with MF had evidences of platelet activation and 2 out of 14 patients with CML had platelet activation. The deficiency of the dense bodies was less frequent than the depletion of the alpha granules (5 out of 11 PV, 4 out of 10 ET, 6 out of 14 CML and 2 out of 3 MF). The low intraplatelet contents of vWF: Ag and FI, more frequently observed in ET and PV, may be the result of platelet activation and in vivo release, but megakaryocyte dysfunction is more likely in myelofibrosis.
Asunto(s)
Antígenos/análisis , Plaquetas/fisiología , Fibrinógeno/análisis , Trastornos Mieloproliferativos/sangre , Factor de von Willebrand/inmunología , Plaquetas/inmunología , Humanos , Leucemia Mieloide/sangre , Trastornos Mieloproliferativos/inmunología , Policitemia Vera/sangre , Mielofibrosis Primaria/sangre , Valores de Referencia , Trombocitemia Esencial/sangreRESUMEN
El crecimiento in vitro de unidades formadoras de colonias granulomonocíticas (UFC-GM) en sangre periférica (SP) y médula ósea (MO) humana requiere de fractores estimuladores denominados actividad estimuladora de colonias (AEC). El ensayo de Pike & Robinson emplea como fuente de AEC capa alimentadora (CA) compuesta por leucocitos de SP inmovilizados en agar. No obstante que este ensayo de bicapa presenta desventajas técnicas es ampliamente utilizado. Los sobrenadantes tisulares y celulares con actividad biológica para la UFC-GM, también conocidos como medios condicionados (MC), eliminan lsos incovenientes teécnicos de la estimulación con CA. En el presente trabajo se prepararon dos MC, uno de CA (MC-CA) y otro de leucocitos estimulados con fitohemaglutinina (MC-LEF). La AEC de ambos MC se comparó con la producida por la CA. Las tres AEC, evaluadas por el número de racimos (agregados celulares con 3 a 39 células) y de colonias (agregados celulares con -> 40 células) presentes en el cultivo, se probaron en células obtenidas de SP de 17 individuos sanos, y en células de SP (17 muestras) y MO (12 muestras) de enfermos con leucemias mieloides. Se encontró que el MC-CA indujo un número significativamente menor de agregados celulares tanto en muestras de sujetos normales como de enfermos leucémicos al compararlo con el ensayo de CA. En muestras de pacientes con leucemia, el crecimiento clonal mediado por el MC-LEF fue similar al encontrado con CA. En cambio, la adición de MC-LEF a muestras de sujetos sanos dio como resultado un número promedio de colonias significativamente menor al observado con CA. Estos resultados indican que el MC-CA es una fuente inapropiada de AEC para muestras provenientes de sujetos normales y de pacientes leucémicos, mientras que la AEC derivada del MC-LEF mantiene adecuadamente el crecimiento de UFC-GM en muestras de enfermos con leucemia, pero no en muestras de personas normales. Basados en estos hallazgos y en los incovenientes técnicos del ensayo de Pike & Robinson, se concluye que el MC-LEF permite una mejor evaluación de la granulomonopoyesis in vitro en pacientes con leucemias mieloides
Asunto(s)
Humanos , Factores Estimulantes de Colonias/sangre , Granulocitos , Técnicas In Vitro , Monocitos , Leucemia Mieloide/sangreRESUMEN
We studied splenic function in children with cancer by quantitation of pitted, or pocked, erythrocytes (pocked RBC count), that is, the percentage of erythrocytes containing one or more membrane-bound vesicles, as determined by phase interference microscopy. The mean pocked RBC count in 93 normal children and adults was 0.49% (range 0% to 2.0%), with only 2.4% of normal subjects having values greater than 1.5%. Mean pocked RBC count in 28 children after splenectomy was 37% (range 3.2% to 81%). Among 181 children with cancer (525 specimens), the mean pocked RBC count was 1.06% (range 0% to 12.6%). Fifty-nine (32%) patients had one or more values greater than 1.5%, and 25 (13.8%) children had measurements greater than 3.0%, a level previously suggested to have clinical significance. Elevated pocked RBC counts (greater than 1.5%) occurred in more than one third of children with Wilms tumor and acute lymphoblastic leukemia, and in both patients with juvenile chronic myelogenous leukemia. Elevations in pocked RBC counts were not related to specific chemotherapy regimens or to disease activity. Mild splenic reticuloendothelial hypofunction occurs in many children with cancer and may contribute to the risk of infection in these patients.
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Leucemia Linfoide/fisiopatología , Sistema Mononuclear Fagocítico/fisiopatología , Neoplasias/fisiopatología , Bazo/fisiopatología , Enfermedad Aguda , Adolescente , Adulto , Niño , Preescolar , Recuento de Eritrocitos , Inclusiones Eritrocíticas/patología , Membrana Eritrocítica/patología , Humanos , Lactante , Leucemia Linfoide/sangre , Leucemia Mieloide/sangre , Neoplasias/sangre , Tumor de Wilms/sangreAsunto(s)
Leucemia Mieloide/sangre , Neutrófilos/fisiología , Animales , Movimiento Celular , HumanosAsunto(s)
Alopurinol/efectos adversos , Anemia Aplásica/inducido químicamente , Azatioprina/efectos adversos , Trasplante de Riñón , Adulto , Anemia Aplásica/terapia , Transfusión Sanguínea , Interacciones Farmacológicas , Humanos , Fallo Renal Crónico/cirugía , Leucemia Mieloide/sangre , Leucocitos , Masculino , Trasplante HomólogoRESUMEN
Peripheral blood from a child with adult-type (Philadelphia chromosome positive) chronic granulocytic leukemia was found to contain large numbers of cells capable of colony formation in tissue culture. The majority of the colonies contained granulocytic cells. The source of these granulocytic colonies was found in a population of myeloblasts, promyelocytes, and myelocytes which could be separated from the more mature granulocytic cells of the peripheral blood by sedimentation of the buffy coat on Ficoll-Hypaque. The predominance of granulocytic colonies is in contrast to our observations previously made on the peripheral blood of children with "juvenile" type(Ph1 chromosome negative)CGL in which large numbers of exclusively monocytic colonies were produced in tissue culture. These current studies, when interpreted in light of relevant clinical data, suggest that the "juvenile" and "adult" types of CGL represent two very different forms of chronic leukemia in childhood. The Ph1 chromosome negative form may be classified as a monocytic leukemia with a granulocytic component but the Ph1 chromosome positive adult form, even when it occurs in a child, appears to be a true granulocytic leukemia.