RESUMEN
Gaucher Disease type 1 (GD1) is a lysosomal disorder that affects many systems. Therapy improves the principal manifestations of the condition and, as a consequence, many patients show a modified phenotype which reflects manifestations of their disease that are refractory to treatment. More generally, it is increasingly recognised that information as to how a patient feels and functions [obtained by patient- reported outcome measurements (PROMs)] is critical to any comprehensive evaluation of treatment. A new set of management goals for GD1 in which both trends are reflected is needed. To this end, a modified Delphi procedure among 25 experts was performed. Based on a literature review and with input from patients, 65 potential goals were formulated as statements. Consensus was considered to be reached when ≥75% of the participants agreed to include that specific statement in the management goals. There was agreement on 42 statements. In addition to the traditional goals concerning haematological, visceral and bone manifestations, improvement in quality of life, fatigue and social participation, as well as early detection of long-term complications or associated diseases were included. When applying this set of goals in medical practice, the clinical status of the individual patient should be taken into account.
Asunto(s)
Enfermedad de Gaucher/complicaciones , Enfermedad de Gaucher/terapia , Calidad de Vida , Consenso , Manejo de la Enfermedad , Europa (Continente)/epidemiología , Enfermedad de Gaucher/epidemiología , Enfermedad de Gaucher/psicología , HumanosRESUMEN
Thrombosis is the most common and a life-threatening complication in patients with Paroxysmal Nocturnal Hemoglobinuria. One-third of patients with PNH experience at least one thromboembolic event during the course of the disease, with thrombosis being the most common cause of death in these patients. The mechanism of thrombosis in PNH is complex and continues to be of great research interest. Since the introduction of C5 complement inhibitors in the treatment of PNH, the incidence of thromboembolic events has decreased substantially. We retrospectively analyzed data concerning the thrombotic episodes of 41 patients with PNH from 14 different national hematology centers in Greece. Sixteen patients (39%) experienced at least one episode of thrombosis, including, seven (43.8%) at diagnosis, seven (43.8%) during the course of the disease and two (12.5%) patients prior to PNH diagnosis. Nearly half of these individuals (n=7, 43.8%) had multiple episodes of thrombosis during the course of their disease. The most common sites of thrombosis were intra-abdominal veins. Three out of 26 patients developed thrombosis while on eculizumab. In none of the 16 patients, the thrombotic event was fatal. Our findings, despite the small number of patients, confirmed that thrombosis continues to be a significant complication of PNH affecting more than one third of the patients.
RESUMEN
The efficacy and toxicity of amifostine (300 mg/m(2) three times a week for three consecutive weeks for a maximum of six courses) was evaluated in 12 patients with primary myelodysplastic syndromes. Dose escalation up to 400 mg/m(2) was allowed to patients who failed to respond. Hemoglobin concentration was increased > or = 1.5 g/dl in two (18%) of the 11 anemic patients. These two patients obtained transfusion independence for 20 weeks. Reticulocyte counts and ANC increased > or = 50% of baseline in four (44%) of the nine patients with reticulocytopenia and in three (25%) of the 12 neutropenic patients. Platelet count increased in three (50%) of the six patients with thrombocytopenia. Progenitor growth of CFU-GMs and BFU-Es improved in 8/12 patients. No major side effects were observed. In conclusion amifostine is well tolerated and can promote the growth of primitive hematopoietic progenitors and ameliorate the cytopenias in MDS patients.
Asunto(s)
Amifostina/uso terapéutico , Síndromes Mielodisplásicos/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Amifostina/efectos adversos , División Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/patología , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/sangreAsunto(s)
Trasplante de Médula Ósea , Quimera/genética , Hibridación Fluorescente in Situ , Macrófagos Alveolares/ultraestructura , Adolescente , Adulto , Trasplante de Médula Ósea/patología , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sexo , Trasplante Homólogo , Cromosoma X , Cromosoma YRESUMEN
Gaucher disease is a lysosomal storage disorder, in which undigested glucosylceramide is deposited in the cytoplasm of mature macrophages, which accumulate in the bone marrow and the reticuloendothelial system. Dendritic cells are bone marrow-derived cells, specialized for the uptake, processing, transport and presentation of antigens to T-lymphocytes. We investigated peripheral blood dendritic cell-precursors, as well as the potential of peripheral blood monocytes and bone marrow-derived progenitor cells, to differentiate into mature dendritic cells in 12 patients with type I Gaucher disease. Results of the 10 adult patients were compared with those of 10 healthy volunteers, matched for age and sex. Six patients were anemic and 9 were thrombocytopenic, but none had severe bone disease. Both myeloid and plasmacytoid dendritic cells of patients with Gaucher disease, as well as the yield of the monocyte-derived dendritic cells, obtained after GM-CSF and IL-4 stimulation, were found significantly decreased, when compared to controls (myeloid dendritic cells: 0.19 +/- 0.07% vs. 0.34 +/- 0.10%, P = 0.009, plasmacytoid dendritic cells: 0.17 +/- 0.12% vs. 0.39 +/- 0.13%, P = 0.004, monocyte-derived dendritic cells: 4.8 +/- 3.5% vs. 8.3 +/- 3.2%, P = 0.036). However, the immunophenotypic profile of dendritic cells, estimated by CD1a, CD40, CD54, CD80, CD83 and HLA-DR expression, the endocytic and allo-stimulatory capacity of the immature, as well as of the TNF-alpha- or lipopolysaccharite-stimulated mature monocyte-derived dendritic cells, was similar to those obtained by healthy controls. In addition, bone marrow-derived CD34+ cells differentiated in the presence of GM-CSF, SCF, TNF-alpha and IL-4 into mature dendritic cells that did not differ in number, phenotype and allo-stimulatory activity from those of controls. Our findings suggest that patients with Gaucher disease exhibit mainly quantitative defects of their dendritic cells' system, demonstrated by decreased circulating dendritic cell precursors of both myeloid and plasmacytoid type. This finding may contribute to the poor immune response against infectious agents and an impaired immune surveillance, associated with an increased risk of developing a neoplastic disease.
Asunto(s)
Células Dendríticas/patología , Enfermedad de Gaucher/patología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Recuento de Células , Diferenciación Celular , Niño , Células Dendríticas/inmunología , Femenino , Enfermedad de Gaucher/inmunología , Humanos , Sistema Inmunológico/patología , Masculino , Persona de Mediana Edad , Monocitos/patología , Células Madre/patologíaRESUMEN
In elderly patients with secondary leukemia, poor therapeutic response and low overall survival have been attributed mainly to age and to the primary resistance of leukemic cells to chemotherapy. Modulation of resistance has been attempted in different studies, but the results have been contradictory. We conducted an open, randomized multicenter clinical trial involving patients more than 60 years old with secondary leukemia preceded by a myelodysplastic syndrome. The induction chemotherapy regimen included idarubicin, cytarabine, and etoposide (group A); randomization involved simultaneous administration of cyclosporin-A per os (group B). Fifty-five patients were evaluated, 26 in group A and 29 in group B. Overall complete remission was achieved in 40% of the patients, 27% vs 52% in groups A and B, respectively (p=0.01). Leukemia-free survival was more favorable in patients who received cyclosporin-A, 12 vs 7 months for groups B and A, respectively (p=0.03). In a follow up period of 30 months, 7 out of 55 patients (13%) were alive, 4 of whom were in complete remission. Five out of the 7 alive patients were randomized in group B and had received cyclosporin-A. Treatment failure was higher in group A [19 of 26 patients (73%)] than in group B with CsA [14 of 29 patients (48%)] (p<0.0001). Treatment-related toxicity/mortality was 13%. Modulation of drug resistance by CsA in elderly people suffering from secondary acute leukemia may improve the outcome of chemotherapy without increasing drug toxicity and treatment-related mortality.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclosporina/administración & dosificación , Leucemia Mieloide/tratamiento farmacológico , Neoplasias Primarias Secundarias/tratamiento farmacológico , Enfermedad Aguda , Administración Oral , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclosporina/efectos adversos , Ciclosporina/uso terapéutico , Citarabina/administración & dosificación , Citarabina/uso terapéutico , Interpretación Estadística de Datos , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Etopósido/uso terapéutico , Femenino , Estudios de Seguimiento , Grecia , Humanos , Idarrubicina/administración & dosificación , Idarrubicina/uso terapéutico , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Inducción de Remisión , Sociedades Médicas , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
All-trans-retinoic acid is an effective induction treatment for acute promyelocytic leukemia. Although retinoic acid is well tolerated by the majority of patients with this disease, a potentially fatal complication of this kind of treatment has been reported: "the retinoic acid syndrome". We describe this syndrome, which occurred in one of our patients and was successfully treated by the administration of dexamethasone.