RESUMEN
OPINION STATEMENT: Phosphatidylinositol 3-kinase (PI3K) inhibitors represent a novel class of agents targeting the key cellular regulatory PI3K/AKT/mTOR pathway involved in crucial functions such as cellular proliferation, cell cycle regulation, protein synthesis, and cell motility. This review starts with an overview of the PI3K pathway and the rationale for its targeting in lymphoma and potential on-target side effects of PI3K inhibition. With three agents now FDA approved for the treatment of relapsed and refractory (R/R) indolent non-Hodgkin lymphoma (iNHL), idelalisib, copanlisib, and duvelisib, we aim to review the pivotal trials leading to their approval as well as their clinical applications according to lymphoma subtypes. Important treatment-related adverse events are also reviewed and a perspective on the clinical role of these agents is provided, as well as some practical guidance on how to prevent, monitor, and manage potential adverse events in the clinic. PI3K inhibitors have an established role in the management of R/R iNHL, but their use and development are hampered by adverse events, particularly when used in combination with other anti-lymphoma therapies. Finally, this review highlights areas in need of more research in order to optimally use these agents in the care of patients with lymphoma.
Asunto(s)
Antineoplásicos/uso terapéutico , Linfoma/tratamiento farmacológico , Terapia Molecular Dirigida , Inhibidores de las Quinasa Fosfoinosítidos-3/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ensayos Clínicos como Asunto , Manejo de la Enfermedad , Humanos , Linfoma/diagnóstico , Linfoma/etiología , Linfoma/mortalidad , Terapia Molecular Dirigida/efectos adversos , Terapia Molecular Dirigida/métodos , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3/administración & dosificación , Inhibidores de las Quinasa Fosfoinosítidos-3/efectos adversos , Transducción de Señal/efectos de los fármacos , Resultado del TratamientoAsunto(s)
Anemia Hemolítica/diagnóstico , Deficiencia de Vitamina B 12/diagnóstico , Adulto , Anemia Hemolítica/etiología , Anemia Hemolítica/fisiopatología , Diagnóstico Diferencial , Fatiga/etiología , Femenino , Humanos , Vitamina B 12/sangre , Deficiencia de Vitamina B 12/complicaciones , Vómitos/etiologíaRESUMEN
Management of hematopoietic stem cell transplant complicated by respiratory failure has been facilitated by the use of extracorporeal membrane oxygenation as a bridge to curative chemotherapeutic options. This is the first report of hematopoietic stem cell transplantation on extracorporeal membrane oxygenation in the adult population. CASE SUMMARY: A 28-year-old woman diagnosed with idiopathic aplastic anemia complicated by acute respiratory distress syndrome secondary to pneumonia required venovenous extracorporeal membrane oxygenation to supplement oxygenation and ventilation. She received hematopoietic stem cell transplantation while she was on extracorporeal membrane oxygenation support. MAIN RESULTS AND CONCLUSION: Delivery of the stem cell through extracorporeal membrane oxygenation circuit was successful in the described patient. There was no sequestered stem cell in extracorporeal membrane oxygenation circuit, and she was found to have 90% donor chimerism suggesting successful engraftment. This report showed that infusion of stem cell through extracorporeal membrane oxygenation circuit is safe and feasible, and our results suggest that successful engraftment is possible.