RESUMEN
INTRODUCTION: Hyperkalemia is common in medicine and requires rapid management. Besides the easily evoked causes such as renal failure, adrenal insufficiency, cell lysis or iatrogenic causes, false or pseudo-hyperkalemia should not be forgotten. OBSERVATIONS: Three patients (1 man, 2 women, aged 78, 84, 88) were managed for thrombocytosis (between 1306 and 2404 G/L) and non-symptomatic hyperkalemia (between 6.1 and 7.7mmol/L) are reported. Kalemia on blood collected in heparin tube was normal (4.4-4.6mmol/L). Therefore, no specific treatment for this pseudohyperkalemia was required. CONCLUSION: The combination of thrombocytosis and non-symptomatic hyperkalemia should suggest the diagnosis of pseudohyperkalemia and should prompt for a control of kalemia on blood collected in heparin tube. The recognition of this diagnosis is important in order to avoid unnecessary and potentially deleterious treatment of hyperkalemia.
Asunto(s)
Hiperpotasemia , Trombocitosis , Femenino , Heparina , Humanos , Hiperpotasemia/diagnóstico , Hiperpotasemia/terapia , Masculino , Potasio , Trombocitosis/diagnóstico , Trombocitosis/terapiaRESUMEN
Chronic lymphoid leukemia (CLL) is characterized by the accumulation of functionally defective CD5-positive B lymphocytes. The clinical course of CLL is highly variable, ranging from a long-lasting indolent disease to an unpredictable and rapidly progressing leukemia requiring treatment. It is thus important to identify novel factors that reflect disease progression or contribute to its assessment. Here, we report on a novel STAT3-mediated pathway that characterizes CLL B cells-extended viability and oxidative stress control. We observed that leukemic but not normal B cells from CLL patients exhibit constitutive activation of an atypical form of the STAT3 signaling factor, phosphorylated on serine 727 (Ser(727)) in the absence of detectable canonical tyrosine 705 (Tyr705)-dependent activation in vivo. The Ser(727)-phosphorylated STAT3 molecule (pSTAT3Ser(727)) is localized to the mitochondria and associates with complex I of the respiratory chain. This pSer(727) modification is further controlled by glutathione-dependent antioxidant pathway(s) that mediate stromal protection of the leukemic B cells and regulate their viability. Importantly, pSTAT3Ser(727), but neither Tyr705-phosphorylated STAT3 nor total STAT3, levels correlate with prolonged in vivo CLL B cells survival. Furthermore, STAT3 activity contributes to the resistance to apoptosis of CLL, but not normal B cells, in vitro. These data reveal that mitochondrial (Mt) pSTAT3Ser(727) overactivity is part of the antioxidant defense pathway of CLL B cells that regulates their viability. Mt pSTAT3Ser(727) appears to be a newly identified cell-protective signal involved in CLL cells survival. Targeting pSTAT3Ser(727) could be a promising new therapeutic approach.
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Leucemia Linfocítica Crónica de Células B/metabolismo , Mitocondrias/metabolismo , Factor de Transcripción STAT3/química , Factor de Transcripción STAT3/metabolismo , Serina/metabolismo , Apoptosis , Linfocitos B/citología , Linfocitos B/metabolismo , Supervivencia Celular , Humanos , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/fisiopatología , Mitocondrias/química , Mitocondrias/genética , Fosforilación , Factor de Transcripción STAT3/genética , Serina/genética , Transducción de SeñalAsunto(s)
Anemia Macrocítica/diagnóstico , Artralgia/etiología , Síndromes Mielodisplásicos/tratamiento farmacológico , Polimialgia Reumática/diagnóstico , Anciano de 80 o más Años , Anemia Macrocítica/tratamiento farmacológico , Deleción Cromosómica , Cromosomas Humanos Par 5 , Femenino , Humanos , Síndromes Mielodisplásicos/diagnóstico , Polimialgia Reumática/tratamiento farmacológico , Pérdida de PesoRESUMEN
A study was conducted to compare the efficiency and toxicity of two peripheral blood stem cell (PBSC) mobilization procedures for newly diagnosed patients with multiple myeloma. Patients from group 1 (n=51) were treated by high-dose cyclophosphamide (HD-CY) plus G-CSF (5 microg/kg/day), and the second group (n=31) by VAD regimen plus G-CSF administration (10 microg/kg/day). Successful mobilization, defined by a minimal count of 2.5 x 10(6) CD34(+) cells/kg collected, was achieved in 96 and 90% of patients in groups 1 and 2, respectively (P=0.15). The mean peripheral blood CD34(+) cells concentration and the mean CD34(+) cells/kg collected were higher in group 2 than in the group 1 (P=0.05). The mean number of leukaphereses necessary to collect a count of 2.5 x 10(6) CD34(+) cells/kg was reduced in group 2 compared to group 1. Adverse events, blood products consumption and time spent in the hospital were significantly greater after HD-CY. In conclusion, VAD plus a G-CSF dose of 10 microg/kg administration seems preferential to HD-CY plus a G-CSF dose of 5 microg/kg for PBSC collection because of equivalent or better efficiency in stem cell mobilization, strong favorable toxicity profile and reduced cost.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Mieloma Múltiple/terapia , Antígenos CD34/biosíntesis , Separación Celular , Ciclofosfamida/metabolismo , Dexametasona/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Citometría de Flujo , Factor Estimulante de Colonias de Granulocitos/metabolismo , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/metabolismo , Células Madre/citología , Factores de Tiempo , Resultado del Tratamiento , Vincristina/uso terapéuticoRESUMEN
We describe a case of acute myocardial ischemia following carmustine treatment during the BEAM regimen. Despite this, full completion of the autologous peripheral stem-cell transplant was possible.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carmustina/efectos adversos , Isquemia Miocárdica/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carmustina/administración & dosificación , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Femenino , Humanos , Linfadenopatía Inmunoblástica/complicaciones , Linfadenopatía Inmunoblástica/terapia , Melfalán/administración & dosificación , Persona de Mediana Edad , Trasplante de Células Madre de Sangre Periférica , Trasplante AutólogoRESUMEN
We report here a very unusual patient with Polycythemia vera treated with Pipobroman who developed severe aplastic anemia following administration of the drug. Six months later, because of lack of response, cyclosporine therapy was given there was rapid and complete hematological recovery, highly suggestive of an immune-mediated mechanism, in this case.
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Anemia Aplásica/inducido químicamente , Anemia Aplásica/tratamiento farmacológico , Antineoplásicos Alquilantes/efectos adversos , Ciclosporina/uso terapéutico , Inmunosupresores/uso terapéutico , Pipobromán/efectos adversos , Policitemia Vera/tratamiento farmacológico , Antineoplásicos Alquilantes/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Pipobromán/uso terapéuticoRESUMEN
B lineage-derived malignant proliferation is a well recognized complication of HIV infection. Acute myeloid leukemias have been reported but no complete review of these cases has been performed. The Medline database was reviewed for the years 1980-1997. Eighteen cases of AML have been reported. When previously known, HIV infection was present for 40 months. In 7 patients HIV infection and AML were diagnosed simultaneously. According to the FAB classification, 5 cases were M2, 8 M4, 5 M5. Extramedullary localizations (skin, testis, spleen) were noticed in 10 patients. Non-treated patients had a survival of 2.7 weeks versus 9.8 months in patients treated with chemotherapy. Pathophysiologic studies were performed in 3 cases: reverse transcriptase activity and p24 antigen were noted in tumoral cultured cells in 1 case; absence of viral particules in culture in another one; absence of cloned DNA provirus integration in blasts cells in a third patient. Based on the observed high rate of M4/M5 (72%) versus 19-36% expected in a non HIV-infected population, we postulate that the association of AML and HIV is not coincidental. The monocytotropism of HIV, the chronic cytokines-mediated activation of monocyte/macrophages, the immunodeficiency may explain this association.
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Infecciones por VIH/complicaciones , Leucemia Mieloide Aguda/complicaciones , Infecciones por VIH/diagnóstico , Humanos , Leucemia Mieloide Aguda/diagnóstico , PronósticoRESUMEN
B-cell lineage-derived high-grade malignant lymphomas are a well-recognized complication of HIV infection. However, isolated cases of unusual hematologic malignancies such as acute myeloid leukemias (AML), multiple myeloma (MM) or plasmacytomas, and chronic leukemias have been reported. This review focuses on these uncommon malignancies supervening in the setting of HIV infection. Eighteen cases of AML have been reported. Extramedullary localizations are frequently noticed. Nontreated patients have a survival of 2.7 weeks, compared with 9.8 months for patients treated with chemotherapy; being HIV-positive is not a contraindication to the treatment of AML. Based on the observed 72% incidence of AML M4 and M5 in an HIV-infected population versus 19% to 36% expected in a non-HIV-infected population, we postulate that the association of AML and HIV is not coincidental. The monocytotropism of HIV, the chronic cytokine-mediated activation of monocytes/macrophages, and the immunodeficiency may explain this association. Twenty-two cases of MM or plasmacytomas have been described, most of them in young patients. Again, extramedullary plasma cell tumors are recorded in many patients. Physiopathologic studies suggest that MM may develop because of an antigen-driven response to the circulating viral antigens. A role for Epstein-Barr virus (EBV) in the pathogenesis, as previously described in high-grade non-Hodgkin's lymphomas, is suggested by the presence of EBV genomes in plasma cell tumors. Finally, a broad spectrum of chronic leukemias derived from B- or T-cell lymphocyte lineage has been reported. These associations seem coincidental.
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Infecciones por VIH/complicaciones , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Mieloide/complicaciones , Mieloma Múltiple/complicaciones , Adolescente , Adulto , Anciano , Femenino , Francia/epidemiología , Infecciones por VIH/epidemiología , Humanos , Incidencia , Leucemia Linfocítica Crónica de Células B/epidemiología , Leucemia Mieloide/epidemiología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/epidemiologíaRESUMEN
Apoptosis of hematopoietic progenitor cells is increased in myelodysplastic syndromes (MDS). We have studied Fas (CD95/Apo-1) antigen expression in 27 MDS patients (RARS 4, RA 3, RAEB 13; RAEB-t 3, CMML 4) and three AML secondary to MDS. We found that the Fas antigen was not expressed on normal bone marrow (BM) CD34+, CD14+, or glycophorin+ cells, and only slightly on CD33+ cells. Patients with MDS had upregulation of Fas expression on total bone marrow nuclear cells (BMMC) (t-test, P = 0.04), CD34+ (P = 0.013), CD33+ (P = 0.04), and glycophorin+ (P = 0.032) BM cells compared to controls. Fas expression did not correlate to the FAB subtype, the Bournemouth score, or to peripheral cytopenias. However, Fas expression intensity on CD34+ cells negatively correlated to the BM blasts number (Spearman, P = 0.01) suggesting that leukemic blasts cells lose Fas antigen expression with progression of myelodysplasia. Using both proliferation assays in liquid cultures and clonogenic progenitor assays in the presence of an agonist anti-Fas MoAb (CH11), we showed that the Fas protein was functional in some patients. Dose-dependent inhibition of DNA synthesis was observed in three out of seven patients studied. CFU-GM and BFU-E colonies suppression in some patients suggested that Fas can induce apoptosis in myeloid and erythroid BM progenitors of MDS patients. The TUNEL technique on BM smears gave a mean of 12.6% +/- 2.5 of bone marrow apoptotic cells in five controls. Patients with MDS had increased bone marrow apoptosis (mean 39% +/- 5.7, t-test, P = 0.012). Four out of 15 (26%) patients studied with a sensitive radiolabeled DNA ladder technique had typical DNA ladders indicative of advanced stages of apoptosis. Massive BM suicide was observed in patients with RA (2/2) and RAEB (8/11), whereas apoptosis rates were normal or low in patients with RAEB-t (3/3) or secondary AMLs (3/3). Moreover, high rates of apoptosis correlated to low Bournemouth score (Spearman, P = 0.01). No statistical correlation could be found between Fas expression and apoptosis rates. Our results confirm the importance of programmed cell death in MDS. The Fas antigen is clearly upregulated on BM cells, but its role in the pathophysiology of apoptosis in myelodysplasia is still unclear, indicating that many factors positively or negatively interfere with the Fas-mediated pathway of apoptosis in vivo and in vitro.
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Antígenos CD/biosíntesis , Apoptosis , Células Madre Hematopoyéticas/inmunología , Células Madre Hematopoyéticas/patología , Síndromes Mielodisplásicos/inmunología , Síndromes Mielodisplásicos/patología , Receptor fas/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Anemia Refractaria/clasificación , Anemia Refractaria/inmunología , Anemia Refractaria/patología , Anemia Refractaria con Exceso de Blastos/clasificación , Anemia Refractaria con Exceso de Blastos/inmunología , Anemia Refractaria con Exceso de Blastos/patología , Antígenos CD/análisis , Médula Ósea/inmunología , Médula Ósea/patología , Células de la Médula Ósea , Células Cultivadas , Ensayo de Unidades Formadoras de Colonias , ADN/análisis , Fragmentación del ADN , Femenino , Células Madre Hematopoyéticas/citología , Humanos , Cariotipificación , Leucemia Mieloide/clasificación , Leucemia Mieloide/inmunología , Leucemia Mieloide/patología , Masculino , Persona de Mediana Edad , Valores de Referencia , Sensibilidad y Especificidad , Receptor fas/análisisRESUMEN
We describe a 50-year-old woman with seropositive rheumatoid arthritis and Sjögren's syndrome who underwent autologous blood stem cell transplantation after relapse of associated non-Hodgkin's lymphoma. This resulted in complete remission not only of the lymphoma, but also the arthritis.
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Artritis Reumatoide/terapia , Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin/terapia , Síndrome de Sjögren/complicaciones , Artritis Reumatoide/etiología , Femenino , Humanos , Linfoma no Hodgkin/complicaciones , Persona de Mediana EdadRESUMEN
Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by a cytopenia related to abnormal proliferation and differentiation of marrow precursor cells. Some subtypes of MDS are associated with thrombocytemia or abnormal megakaryopoiesis and certain specific karyotypic abnormalities. We report on four cases of MDS with normal or elevated blood platelet count and a recurring abnormality in chromosome 1p34. The gene involved appears to be different from c-mpl and TPO.