Asunto(s)
Bortezomib/uso terapéutico , Dexametasona/uso terapéutico , Doxorrubicina/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Bortezomib/farmacología , Dexametasona/farmacología , Doxorrubicina/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Resultado del TratamientoAsunto(s)
Mieloma Múltiple , Inhibidores de Proteasoma , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compuestos de Boro , Dexametasona/uso terapéutico , Glicina/análogos & derivados , Humanos , Lenalidomida/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Inhibidores de Proteasoma/uso terapéuticoRESUMEN
High-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) is the standard of care for eligible multiple myeloma (MM) patients with improved progression-free and overall survival. We reviewed the ambulatory care unit pathway for MM patients who underwent HDT/ASCT in a tertiary hospital to assess safety efficacy and outcomes. We concluded that the ambulatory care model offered for MM patients undergoing HDT/ASCT is a safe alternative pathway and highlighted further improvements.
Asunto(s)
Antineoplásicos/efectos adversos , Mieloma Múltiple/terapia , Trasplante de Células Madre/efectos adversos , Trasplante Autólogo/efectos adversos , Adulto , Anciano , Atención Ambulatoria , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
PURPOSE: Immune dysregulation is described in multiple myeloma. While preclinical models suggest a role for altered T-cell immunity in disease progression, the contribution of immune dysfunction to clinical outcomes remains unclear. We aimed to characterize marrow-infiltrating T cells in newly diagnosed patients and explore associations with outcomes of first-line therapy. EXPERIMENTAL DESIGN: We undertook detailed characterization of T cells from bone marrow (BM) samples, focusing on immune checkpoints and features of immune dysfunction, correlating with clinical features and progression-free survival. RESULTS: We found that patients with multiple myeloma had greater abundance of BM regulatory T cells (Tregs) which, in turn, expressed higher levels of the activation marker CD25 compared with healthy donors. Patients with higher frequencies of Tregs had shorter PFS and a distinct Treg immune checkpoint profile (increased PD-1, LAG-3) compared with patients with lower frequencies of Tregs. Analysis of CD4 and CD8 effectors revealed that low CD4effector (CD4eff):Treg ratio and increased frequency of PD-1-expressing CD4eff cells were independent predictors of early relapse over and above conventional risk factors, such as genetic risk and depth of response. Ex vivo functional analysis and RNA sequencing revealed that CD4 and CD8 cells from patients with greater abundance of CD4effPD-1+ cells displayed transcriptional and secretory features of dysfunction. CONCLUSIONS: BM-infiltrating T-cell subsets, specifically Tregs and PD-1-expressing CD4 effectors, negatively influence clinical outcomes in newly diagnosed patients. Pending confirmation in larger cohorts and further mechanistic work, these immune parameters may inform new risk models, and present potential targets for immunotherapeutic strategies.
Asunto(s)
Médula Ósea/patología , Linfocitos Infiltrantes de Tumor/inmunología , Mieloma Múltiple/etiología , Mieloma Múltiple/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T Reguladores/inmunología , Biomarcadores de Tumor , Estudios de Casos y Controles , Citocinas/metabolismo , Femenino , Humanos , Activación de Linfocitos/inmunología , Recuento de Linfocitos , Linfocitos Infiltrantes de Tumor/metabolismo , Linfocitos Infiltrantes de Tumor/patología , Masculino , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Pronóstico , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/patología , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/patologíaRESUMEN
OBJECTIVE: Cytomegalovirus (CMV) is an opportunistic herpesvirus, and reactivation of infection is possible in immunocompromised patients. Historically, the risk for haematology patients is restricted to those treated with an allogeneic transplant or T-cell depleting agents. Bortezomib is a highly efficacious proteasome inhibitor widely used to treat multiple myeloma and light chain (AL) amyloidosis patients. The objective of this small prospective study was to quantify the risk of CMV reactivation associated with bortezomib treatment. METHODS: Fifty-seven consecutive multiple myeloma or AL amyloidosis patients commencing bortezomib-based therapy were included. Viral copy numbers were established at baseline and then at fortnightly intervals during treatment. Pre-emptive anti-viral treatment was initiated in patients with a viral load >7500 copies/mL. RESULTS: Reactivation of CMV was detected in 39% (n = 12/31) of seropositive bortezomib treated patients compared with 0% of CMV seronegative patients. Detectable DNAemia developed during the first two cycles of treatment in 83% (n = 10/12) patients. Anti-viral treatment was initiated in 42% (n = 5/12), but no cases of active CMV disease were seen. CONCLUSION: This study suggests that there is a substantial risk of CMV reactivation in CMV-seropositive plasma cell dyscrasia patients treated with bortezomib.
Asunto(s)
Antineoplásicos/efectos adversos , Bortezomib/efectos adversos , Infecciones por Citomegalovirus/etiología , Citomegalovirus , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/complicaciones , Mieloma Múltiple/complicaciones , Activación Viral/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/uso terapéutico , Citomegalovirus/efectos de los fármacos , Citomegalovirus/inmunología , Femenino , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/diagnóstico , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Estudios Prospectivos , Carga ViralAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Anciano , Ensayos Clínicos como Asunto , Resistencia a Antineoplásicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Recurrencia , Estudios Retrospectivos , Centros de Atención Terciaria , Resultado del TratamientoRESUMEN
Hyponatraemia is the most common electrolyte disturbance encountered in clinical practice. Several causes of hyponatraemia are recognised and in many patients the aetiology may be multifactorial. An important cause is water intoxication and this is often iatrogenic. We present three patients, all of whom suffered from multiple myeloma, who illustrate different aspects of hyponatraemia, its causes and management.