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1.
Science ; 366(6469): 1143-1149, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31780560

RESUMO

Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.


Assuntos
Enterococcus/crescimento & desenvolvimento , Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro/microbiologia , Transplante de Células-Tronco Hematopoéticas , Lactose/metabolismo , Idoso , Animais , Disbiose , Enterococcus/genética , Enterococcus/metabolismo , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Intestinos/microbiologia , Masculino , Camundongos , Microbiota , Pessoa de Meia-Idade , RNA Ribossômico 16S , Análise de Sequência de RNA , Transplante Homólogo
2.
Bone Marrow Transplant ; 48(11): 1444-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23749109

RESUMO

Chemotherapy plus G-CSF (C+G) and G-CSF alone are two of the most common methods used to mobilize CD34(+) cells for autologous hematopoietic SCT (AHSCT). In order to compare and determine the real-world outcomes and costs of these strategies, we performed a retrospective study of 226 consecutive patients at 11 medical centers (64 lymphoma, 162 multiple myeloma), of whom 55% of lymphoma patients and 66% of myeloma patients received C+G. Patients with C+G yielded more CD34(+) cells/day than those with G-CSF alone (lymphoma: average 5.51 × 10(6) cells/kg on day 1 vs 2.92 × 10(6) cells/kg, P=0.0231; myeloma: 4.16 × 10(6) vs 3.69 × 10(6) cells/kg, P<0.00001) and required fewer days of apheresis (lymphoma: average 2.11 vs 2.96 days, P=0.012; myeloma: 2.02 vs 2.83 days, P=0.0015), although nearly all patients ultimately reached the goal of 2 × 10(6) cells/kg. With the exception of higher rates of febrile neutropenia in myeloma patients with C+G (17% vs 2%, P<0.05), toxicities and other outcomes were similar. Mobilization with C+G cost significantly more (lymphoma: median $10,300 vs $7300, P<0.0001; myeloma: $8800 vs $5600, P<0.0001), although re-mobilization adds $6700 for drugs alone. Our results suggest that although both C+G and G-CSF alone are effective mobilization strategies, C+G may be more cost-effective for patients at high risk of insufficient mobilization.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/economia , Fator Estimulador de Colônias de Granulócitos/economia , Mobilização de Células-Tronco Hematopoéticas/economia , Transplante de Células-Tronco Hematopoéticas/economia , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab , Transplante Autólogo/economia , Transplante Autólogo/métodos , Resultado do Tratamento , Adulto Jovem
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