RESUMEN
BACKGROUND: Reductions in transfusion requirements/improvements in hematologic parameters have been associated with iron chelation therapy in transfusion-dependent patients, including those with myelodysplastic syndromes; data on there reductions/improvements have been limited to case reports and small studies. DESIGN AND METHODS: To explore this observation in a large population of patients, we report a post-hoc analysis evaluating hematologic response to deferasirox in a cohort of iron-overloaded patients with myelodysplastic syndromes enrolled in the Evaluation of Patients' Iron Chelation with Exjade(®) (EPIC) study using International Working Group 2006 criteria. RESULTS: Two-hundred and forty-seven, 100 and 50 patients without concomitant medication for myelodysplastic syndromes were eligible for analysis of erythroid, platelet and neutrophil responses, respectively. Erythroid, platelet and neutrophil responses were observed in 21.5% (53/247), 13.0% (13/100) and 22.0% (11/50) of the patients after a median of 109, 169 and 226 days, respectively. Median serum ferritin reductions were greater in hematologic responders compared with non-responders at end of study, although these differences were not statistically significant. A reduction in labile plasma iron to less than 0.4 µmol/L was observed from week 12 onwards; this change did not differ between hematologic responders and non-responders. CONCLUSIONS: This analysis suggests that deferasirox treatment for up to 1 year could lead to improvement in hematologic parameters in some patients with myelodysplastic syndromes.
Asunto(s)
Benzoatos/uso terapéutico , Plaquetas/patología , Hemoglobinas/análisis , Sobrecarga de Hierro/tratamiento farmacológico , Síndromes Mielodisplásicos/complicaciones , Neutrófilos/patología , Reacción a la Transfusión , Triazoles/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Plaquetas/efectos de los fármacos , Niño , Deferasirox , Femenino , Estudios de Seguimiento , Humanos , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/mortalidad , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/terapia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/etiología , Recurrencia Local de Neoplasia/mortalidad , Neutrófilos/efectos de los fármacos , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Adulto JovenAsunto(s)
Cardiopatías/etiología , Sobrecarga de Hierro/etiología , Síndromes Mielodisplásicos/terapia , Reacción a la Transfusión , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana EdadRESUMEN
Assays detecting antigen (Ag)-specific T-cell responses in immune-mediated processes are increasingly employed to understand disease pathogenesis and immune staging. The quantity and quality of starting peripheral blood mononuclear cell (PBMC) preparations are important factors in the performance of such assays. We therefore compared final PBMC yield and function by modifying parameters at the blood drawing, storage and processing steps. While drawing blood in vacuum-driven tubes or syringes and separating PBMCs on density gradients using standard or membrane (Leucosep) tubesmade no difference, storing tubes for 18 h without any agitation led to PBMC preparations contaminated with granulocytes and decreased interferon (IFN)-gamma enzyme-linked immunospot (ELISpot) responses. Even agitated blood showed a trend towards reduced ELISpot responses and increased human leukocyte Ag (HLA) multimer readouts when stored for 18 h compared to 3 h. These changes were reduced by diluting blood prior to storage. Washing PBMCs with media containing 10% human serum increased PBMC yields by 40.5%, without affecting ELISpot responses and multimer counts. However, washes with > 10% human serum decreased multimer counts, with no additional improvement in PBMC yields. These findings may be relevant for optimizing and harmonizing PBMC processing procedures for T-cell assays.
Asunto(s)
Recolección de Muestras de Sangre/métodos , Separación Celular/métodos , Técnicas para Inmunoenzimas/métodos , Leucocitos Mononucleares/citología , Linfocitos T/citología , Linfocitos T/inmunología , Adulto , Conservación de la Sangre/métodos , Centrifugación por Gradiente de Densidad , Femenino , Granulocitos/citología , Granulocitos/inmunología , Antígeno HLA-A2/sangre , Antígeno HLA-A2/inmunología , Humanos , Interferón gamma/inmunología , Recuento de Leucocitos , Leucocitos Mononucleares/inmunología , MasculinoRESUMEN
The prospective 1-year EPIC study enrolled 341 patients with myelodysplastic syndromes (MDS); although baseline iron burden was >2500ng/mL, approximately 50% were chelation-naïve. Overall median serum ferritin decreased significantly at 1 year (p=0.002). Decreases occurred irrespective of whether patients were chelation-naïve or previously chelated; changes were dependent on dose adjustments and ongoing iron intake. Sustained reductions in labile plasma iron were observed. Discontinuation rate (48.7%) and adverse event profile were consistent with previously reported deferasirox data in MDS. Alanine aminotransferase levels decreased significantly; change correlated significantly with reduction in serum ferritin (p<0.0001). This large dataset prospectively confirms the efficacy and well characterizes the safety profile of deferasirox in MDS.
Asunto(s)
Benzoatos/uso terapéutico , Transfusión Sanguínea , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/tratamiento farmacológico , Síndromes Mielodisplásicos/complicaciones , Triazoles/uso terapéutico , Adolescente , Adulto , Anciano , Alanina Transaminasa/sangre , Benzoatos/efectos adversos , Niño , Preescolar , Deferasirox , Femenino , Ferritinas/sangre , Humanos , Quelantes del Hierro/efectos adversos , Sobrecarga de Hierro/complicaciones , Masculino , Persona de Mediana Edad , Triazoles/efectos adversos , Adulto JovenRESUMEN
ESAs are increasingly used to treat anemia of lower risk MDS, even before RBC transfusion requirement. From a previously published patient cohort treated with ESAs, we selected 112 patients with de novo low or int-1 IPSS MDS with Hb<10 g/dl, serum EPO<500 UI/l and who had never been transfused. Erythroid response rate at 12 weeks was 63.1% (IWG 2006). In multivariate analysis, an interval between diagnosis and ESA onset<6 months, Hb level>9 g/dl, and serum EPO<100 UI/l predicted better response to ESA while shorter interval between diagnosis and ESA onset (p=0.01), lower serum EPO (p=0.04) and WHO diagnosis of RCMD-RS (p=0.03) were associated with longer response. Median interval from diagnosis to transfusion dependency was 80 months and 35 months, respectively, in patients with onset of ESA < 6 months and ≥ 6 months from diagnosis (p=0.007). Those results support early onset of ESA in lower risk MDS, to better avoid the consequences of anemia. Early introduction of ESA may also delay the need for RBC transfusions, hypothetically by slowing the disease course, but prospective studies are required to further assess this point.