RESUMEN
Stem cell transplant (SCT) outcomes in high-risk and relapsed/refractory (R/R) pediatric acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) have been historically poor. Cord blood (CB) allows T-cell replete CB transplant (TRCB), enabling enhanced graft-versus-leukemia. We consecutively collected data from 367 patients undergoing TRCB (112 patients) or other cell source (255 patients) SCT for pediatric AML/MDS in the United Kingdom and Ireland between January 2014 and December 2021. Data were collected about the patient's demographics, disease, and its treatment; including previous transplant, measurable residual disease (MRD) status at transplant, human leukocyte antigen-match, relapse, death, graft versus host disease (GvHD), and transplant-related mortality (TRM). Univariable and multivariable analyses were undertaken. There was a higher incidence of poor prognosis features in the TRCB cohort: 51.4% patients were MRD positive at transplant, 46.4% had refractory disease, and 21.4% had relapsed after a previous SCT, compared with 26.1%, 8.6%, and 5.1%, respectively, in the comparator group. Event free survival was 64.1% within the TRCB cohort, 50% in MRD-positive patients, and 79% in MRD-negative patients. To allow for the imbalance in baseline characteristics, a multivariable analysis was performed where the TRCB cohort had significantly improved event free survival, time to relapse, and reduced chronic GvHD, with some evidence of improved overall survival. The effect appeared similar regardless of the MRD status. CB transplant without serotherapy may be the optimal transplant option for children with myeloid malignancy.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Trastornos Mieloproliferativos , Humanos , Niño , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre/efectos adversos , Síndromes Mielodisplásicos/patología , Enfermedad Injerto contra Huésped/etiología , Leucemia Mieloide Aguda/patología , RecurrenciaAsunto(s)
Anticuerpos Biespecíficos/uso terapéutico , Leucemia Bifenotípica Aguda/tratamiento farmacológico , Neoplasia Residual/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Anciano , Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Biespecíficos/farmacología , Antígenos CD19/efectos de los fármacos , Antígenos CD19/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada/métodos , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , N-Metiltransferasa de Histona-Lisina/efectos de los fármacos , N-Metiltransferasa de Histona-Lisina/genética , Humanos , Lactante , Leucemia Bifenotípica Aguda/genética , Leucemia Bifenotípica Aguda/patología , Masculino , Proteína de la Leucemia Mieloide-Linfoide/efectos de los fármacos , Proteína de la Leucemia Mieloide-Linfoide/genética , Neoplasia Residual/genética , Neoplasia Residual/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Supervivencia sin Progresión , Inducción de Remisión , Resultado del TratamientoRESUMEN
The optimal dosage information to improve the prognosis of invasive fungal infections in children and neonates is still limited and current dosing strategies are supported mainly by adult studies and extrapolation. Significant progress has been made to address this need in the last decade. Pre-clinical models and pharmacokinetic-pharmacodynamic (PK-PD) bridging studies supported by pediatric pharmacokinetic studies have investigated optimal dosing regimens for neonates and children. Here, we review the rationale for various antifungal regimens in infants and children.
Asunto(s)
Antifúngicos/farmacocinética , Equinocandinas/farmacocinética , Polienos/farmacocinética , Triazoles/farmacocinética , Adulto , Antifúngicos/uso terapéutico , Niño , Equinocandinas/uso terapéutico , Humanos , Pediatría , Farmacología Clínica , Polienos/uso terapéutico , Triazoles/uso terapéuticoRESUMEN
Neonates are vulnerable to adverse drug reactions but reports of these events are relatively infrequent. Reporting can be increased by adapting a number of standard techniques to the unique features of neonatal care and pathology. However, clinicians and parents will be reluctant to report information about harms in the absence of mechanisms to ensure that reports affect clinical practice. Improved reporting will depend on education and cultural change that are informed by research about pharmacovigilance in neonatal settings. The efficient use of neonatal adverse drug reaction reports will require harmonization of terminology and interoperable databases.
