RESUMO
Hemophilia A is an X-linked bleeding disorder caused by defects in the gene encoding factor VIII (FVIII). Routine prophylaxis with exogenous FVIII requires frequent intravenous injections. One of the most challenging issues in the treatment of hemophilia A is the development of alloantibodies against infused FVIII. Presence of inhibitors results in an ineffective factor replacement therapy and increases the risk of morbidity and mortality in these patients. Therefore, there is growing interest in the development of new strategies for the prophylaxis and prevention of bleeding in patients with hemophilia to circumvent these drawbacks. Emicizumab (ACE-910; Roche, Genentech and Chugai Pharmaceutical) is a recombinant humanized bispecific antibody that restores the function of missing FVIII by bridging activated FIX and FX, simulating the cofactor function of FVIII.
Assuntos
Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Hemofilia A/tratamento farmacológico , Fator VIII , HumanosRESUMO
The response evaluation after autologous stem-cell transplantation (ASCT) is usually performed at day +100 in patients with multiple myeloma (MM). A recent report suggests that improvement in the response can be observed beyond day +100. The aim of the present study has been to evaluate the rate of improved response and outcome beyond day +100 after ASCT, with and without maintenance therapy. One hundred and forty-four patients who underwent single ASCT with chemosensitive disease and achieved less than CR at day 100 post ASCT were evaluated. Seventy-four patients (51.4%) did not receive any maintenance with only one of them showing an upgrade in the response. The remaining 70 patients (48.6%) received maintenance therapy; eleven of them (15.7%) improved their response beyond day +100. The outcome of these patients was better than those who did not upgrade their response in both progression-free survival and overall survival (P=0.019 and P=0.031, respectively). In conclusion, the improvement in response beyond day +100 after ASCT in patients not receiving any therapy is exceedingly rare. A minority of patients receiving maintenance therapy after ASCT upgrades their response and this finding is associated with better outcome.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Quimioterapia de Manutenção , Mieloma Múltiplo/terapia , Adulto , Idoso , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Análise de Sobrevida , Fatores de Tempo , Transplante Autólogo , Resultado do TratamentoAssuntos
Calreticulina/genética , Mutação , Mielofibrose Primária/genética , Receptores de Trombopoetina/genética , Análise Mutacional de DNA , Europa (Continente) , Seguimentos , Humanos , Incidência , Janus Quinase 2/genética , Mielofibrose Primária/complicações , Mielofibrose Primária/diagnóstico , Fatores de Risco , Trombocitemia Essencial/genética , Trombose/complicações , Trombose/genética , Resultado do TratamentoRESUMO
Variations in the intensity of high-latitude Northern Hemisphere summer insolation, driven largely by precession of the equinoxes, are widely thought to control the timing of Late Pleistocene glacial terminations. However, recently it has been suggested that changes in Earth's obliquity may be a more important mechanism. We present a new speleothem-based North Atlantic marine chronology that shows that the penultimate glacial termination (Termination II) commenced 141,000 +/- 2500 years before the present, too early to be explained by Northern Hemisphere summer insolation but consistent with changes in Earth's obliquity. Our record reveals that Terminations I and II are separated by three obliquity cycles and that they started at near-identical obliquity phases.
