RESUMO
Patients with acute myeloid leukaemia (AML) have a five-year survival rate of 28·7%. Natural killer (NK)-cell have anti-leukaemic activity. Here, we report on a series of 13 patients with high-risk R/R AML, treated with repeated infusions of double-bright (CD56bright /CD16bright ) expanded NK cells at an academic centre in Brazil. NK cells from HLA-haploidentical donors were expanded using K562 feeder cells, modified to express membrane-bound interleukin-21. Patients received FLAG, after which cryopreserved NK cells were thawed and infused thrice weekly for six infusions in three dose cohorts (106 -107 cells/kg/infusion). Primary objectives were safety and feasibility. Secondary endpoints included overall response (OR) and complete response (CR) rates at 28-30 days after the first infusion. Patients received a median of five prior lines of therapy, seven with intermediate or adverse cytogenetics, three with concurrent central nervous system (CNS) leukaemia, and one with concurrent CNS mycetoma. No dose-limiting toxicities, infusion-related fever, or cytokine release syndrome were observed. An OR of 78·6% and CR of 50·0% were observed, including responses in three patients with CNS disease and clearance of a CNS mycetoma. Multiple infusions of expanded, cryopreserved NK cells were safely administered after intensive chemotherapy in high-risk patients with R/R AML and demonstrated encouraging outcomes.
Assuntos
Antígeno CD56/análise , Imunoterapia Adotiva/métodos , Células Matadoras Naturais/transplante , Leucemia Mieloide Aguda/terapia , Receptores de IgG/análise , Adolescente , Adulto , Brasil/epidemiologia , Antígeno CD56/imunologia , Criança , Feminino , Proteínas Ligadas por GPI/análise , Proteínas Ligadas por GPI/imunologia , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunoterapia Adotiva/efeitos adversos , Células Matadoras Naturais/imunologia , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/imunologia , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Receptores de IgG/imunologia , Adulto JovemRESUMO
O diabetes insipidus (DI) central é uma síndrome caracterizada pela incapacidade de concentração urinária devido à deficiência do hormônio antidiurético. O envolvimento do sistema nervoso central é frequente nas leucemias, mas a ocorrência de DI é rara e confere pior prognóstico. A patogênese do DI na leucemia não é totalmente conhecida, mas a infiltração do eixo hipotálamo-hipofisário por células leucêmicas parece ser um fator responsável. O presente relato descreve o caso de um paciente que apresentou DI como primeira manifestação de leucemia mieloide aguda e que evoluiu com dificuldades de ajustes do sódio sérico, da poliúria e da reposição volêmica, necessitando de permanência prolongada em unidade de cuidados intensivos(AU)
Central diabetes insipidus (DI) is a syndrome characterized by the inability to concentrate urine due to a lack of antidiuretic hormone. Involvement of the central nervous system is common in acute leukemia, but the occurrence of DI is rare and determines a worse prognosis. The pathogenesis of DI in leukemia has not been fully understood yet, but infiltration of the hypothalamic-pituitary axis by leukemic cells seems to be involved. This report describes a case of a patient who presented with DI as the first manifestation of acute myeloid leukemia. Difficulties in the management of serum sodium, fluid replacement and polyuria led to prolonged length of stay in an intensive care unit(AU)