RESUMEN
A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint. Flow cytometry and next-generation sequencing were performed to identify predictors of response. The final evaluation comprised 184 patients; 84% non-del(5q), 16% isolated del(5q); median follow-up: 70.7 months. In arm A and B, 39 and 41% of patients achieved HI-E; median time-to-HI-E: 3.2 months for both arms, median duration of-HI-E: 9.8 months. HI-E was significantly lower in non-del(5q) vs. del(5q): 32% vs. 80%. The same accounted for transfusion independency-at-week 24 (16% vs. 67%), but similar in both arms. Apart from presence of del(5q), high percentages of bone marrow lymphocytes and progenitor B-cells, a low number of mutations, absence of ring sideroblasts, and SF3B1 mutations predicted HI-E. In conclusion, lenalidomide induced HI-E in patients with non-del(5q) and del(5q) MDS without additional effect of ESA/G-CSF. The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10).
Asunto(s)
Hematínicos , Síndromes Mielodisplásicos , Humanos , Lenalidomida/farmacología , Hematínicos/farmacología , Eritropoyesis , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/genética , Factor Estimulante de Colonias de Granulocitos/farmacología , Deleción Cromosómica , Cromosomas Humanos Par 5/genética , Resultado del TratamientoRESUMEN
Post-transfusion purpura (PTP) is a rare, but severe transfusion reaction in which both donor and autologous platelets are sequestered due to immunization against HPA-1a antigens in HPA-1a negative recipients (HPA: human platelet antigens). We describe a patient who developed PTP during induction therapy for acute myeloid leukaemia. The pitfalls, delays in diagnosing and therapy options of this serious transfusion reaction are discussed.
Asunto(s)
Púrpura/etiología , Trombocitopenia/inmunología , Reacción a la Transfusión/complicaciones , Antígenos de Plaqueta Humana , Transfusión Sanguínea , Femenino , Humanos , Integrina beta3 , Leucemia Mieloide Aguda/terapia , Persona de Mediana Edad , Trombocitopenia/diagnósticoAsunto(s)
Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Fusión Oncogénica/antagonistas & inhibidores , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Pirimidinas/uso terapéutico , Tiazoles/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Asparaginasa/administración & dosificación , Terapia Combinada , Citarabina/administración & dosificación , Dasatinib , Daunorrubicina/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Hibridación Fluorescente in Situ , Masculino , Metotrexato/administración & dosificación , Mitoxantrona/administración & dosificación , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/genética , Neutropenia/inducido químicamente , Neutropenia/tratamiento farmacológico , Proteínas de Fusión Oncogénica/análisis , Proteínas de Fusión Oncogénica/genética , Trasplante de Células Madre de Sangre Periférica , Leucemia-Linfoma Linfoblástico de Células T Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/enzimología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/cirugía , Prednisona/administración & dosificación , Inducción de Remisión , Rotura del Bazo/etiología , Rotura del Bazo/cirugía , Vincristina/administración & dosificación , Adulto JovenAsunto(s)
Anemia de Células Falciformes/complicaciones , Hipertensión Pulmonar/complicaciones , Trombofilia/complicaciones , Adulto , Anemia de Células Falciformes/sangre , Ecocardiografía/métodos , Femenino , Hemólisis , Humanos , Hipertensión Pulmonar/sangre , Masculino , Persona de Mediana Edad , Protrombina/metabolismo , Arteria Pulmonar/patología , Cintigrafía/métodos , Factores de Riesgo , Trombofilia/sangre , Trombosis/complicacionesRESUMEN
BACKGROUND: Lymphoproliferative disorder (LPD) caused by Epstein-Barr virus (EBV) is a severe complication of bone marrow transplantation. The EBV strain causing LPD is of either donor or recipient origin, however, available data are limited to only a small number of cases. To obtain solid evidence, comparison of the EBV strain that caused the EBV-LPD with pre-stem cell transplantation (SCT) EBV strains of donor and recipient is imperative. Available techniques rely on the production of EBV transformed lymphoblastoid cell lines and lack sensitivity. OBJECTIVE: The aim of this study was to develop a simple method for EBV sequence analysis on mouth washings (MWs) and peripheral blood mononuclear cells (PBMCs). STUDY DESIGN: EBV DNA was extracted from MWs and PBMCs that were collected from 20 healthy individuals. DNA was used for sequence analysis, using a polymerase chain reaction for the C-terminus of the LMP-1 gene. RESULTS: In seropositive individuals EBV DNA could be detected in 11/14 (79%) MWs and in 13/14 (93%) PBMC samples. Sequence analysis showed that in 11 out of 14 (79%) healthy individuals sequence patterns could be established. In these 11 healthy individuals 13 sequence patterns could be detected. Eleven of these 13 patterns (84.6%) were unique. These results encouraged us to explore the feasibility of this method on EBV DNA isolated from plasma from 9 EBV-LPD patients at time of EBV reactivation. In 7 EBV-LPD patients 8 sequence patterns were detected. Six out of 8 sequence patterns (75%) were unique. CONCLUSION: Our method is suitable for strain identification and we intend to use this technique to evaluate EBV origin in EBV-LPD patients.
