RESUMEN
Adoptive immunotherapies have been developed for antiviral agent-refractory cytomegalovirus (CMV) disease after stem cell transplantation (SCT). However, the application of such strategies is limited, particularly in terms of need for donor cooperation regarding blood sampling and inaccessibility in the setting of cord blood transplantation. Herein, we describe the first successful treatment of antiviral agent-refractory CMV enteritis after allogeneic SCT by the infusion of ex vivo-expanded donor-derived CD4(+) lymphocytes obtained from the recipient's peripheral blood.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Citomegalovirus/aislamiento & purificación , Enteritis/tratamiento farmacológico , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Donantes de Sangre , Citomegalovirus/fisiología , Infecciones por Citomegalovirus/patología , Humanos , Masculino , Persona de Mediana Edad , Trasplante Homólogo/efectos adversos , Activación ViralRESUMEN
This retrospective study was conducted in Japan to determine the incidence, risk factors and outcomes of sinusoidal obstruction syndrome (SOS) after allogeneic hematopoietic stem cell transplantation (HSCT). Among 4290 patients undergoing allogeneic HSCT between 1999 and 2010, 462 were diagnosed with SOS according to the Seattle criteria (cumulative incidence, 10.8%). The cumulative incidence of SOS diagnosed by the modified Seattle criteria was 9.3%. Of 462 patients, 107 met the Baltimore criteria and 168 had severe SOS with renal and/or respiratory failure. The median onset for SOS was 12 days after HSCT (range, -2-30). Overall survival at day 100 was 32% for SOS and 15% for severe SOS. Multivariate analyses showed that significant independent risk factors for SOS were the number of HSCTs, age, performance status, hepatitis C virus-seropositivity, advanced disease status and myeloablative regimen. SOS was highly associated with overall mortality (hazard ratio, 2.09; P<0.001). Our retrospective survey showed that the cumulative incidence of SOS in Japan was 10.8%, similar to that previously reported in Western countries, and that the overall survival of patients who developed SOS was low. Furthermore, several risk factors were identified. Preventive and therapeutic strategies for high-risk SOS patients must be established to improve overall survival.
Asunto(s)
Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Adolescente , Adulto , Factores de Edad , Aloinjertos , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Neoplasias Hematológicas/sangre , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Enfermedad Veno-Oclusiva Hepática/sangre , Enfermedad Veno-Oclusiva Hepática/etiología , Enfermedad Veno-Oclusiva Hepática/mortalidad , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
OBJECTIVE: POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare multisystem disease characterised by plasma cell dyscrasia and overproduction of vascular endothelial growth factor (VEGF). VEGF is assumed to be useful in monitoring disease activity, because VEGF levels usually decrease after treatment. However, there is no study to investigate whether the extent of decrease in VEGF correlates with clinical outcome. We tested the predictive efficacy of serum VEGF levels in POEMS syndrome. METHOD: This was an institutional review board approved retrospective observational cohort study of 20 patients with POEMS monitored regularly for more than 12â months (median follow-up, 87â months) after treatment onset using our prospectively accumulated database of POEMS from 1999 to 2015. Patients were treated by autologous peripheral blood stem cell transplantation or thalidomide administration. Serum VEGF was measured by ELISA. Outcome measures included clinical and laboratory findings and relapse-free survival. RESULTS: Serum VEGF levels decreased rapidly after treatment, and stabilised by 6â months post treatment. Patients with normalised serum VEGF levels (<1040â pg/mL) at 6â months showed prolonged relapse-free survival (HR=12.81, 95% CI 2.691 to 90.96; p=0.0001) and greater later clinical improvement. The rate of serum VEGF reduction over the first 6â months post treatment correlated with increased grip strength, serum albumin levels, and compound muscle action potential amplitudes at 12â months. CONCLUSIONS: Serum VEGF level at 6â months post treatment is a predicative biomarker for disease activity and prognosis in POEMS syndrome. Serum VEGF could be used as a surrogate endpoint for relapse-free survival or clinical or laboratory improvement of POEMS syndrome for clinical trials.
Asunto(s)
Síndrome POEMS/sangre , Síndrome POEMS/terapia , Trasplante de Células Madre de Sangre Periférica , Talidomida/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
Severe hyponatremia is a critical electrolyte abnormality in allogeneic stem cell transplantation (allo-SCT) recipients and >50% of cases of severe hyponatremia are caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Here, we present a patient with rapidly progressive severe hyponatremia as an initial sign and symptom of human herpesvirus-6-associated post-transplantation acute limbic encephalitis (HHV-6 PALE) after allo-SCT. A 45-year-old woman with acute lymphoblastic leukemia received unrelated bone marrow transplantation from a one locus-mismatched donor at the DR locus. On day 21, she developed a generalized seizure and loss of consciousness with severe hyponatremia, elevated serum antidiuretic hormone (ADH), and decreased serum osmolality. A high titer of HHV-6 DNA was detected in cerebrospinal fluid. Treatment with foscarnet sodium and hypertonic saline was started with improvement of neurological condition within several days. Although an elevated serum ADH, low serum osmolality, and high urinary osmolality persisted for 2 months, she had no other recurrent symptoms of encephalitis. Our experience suggests that hyponatremia accompanied by SIADH should be recognized as a prodromal or concomitant manifestation of HHV-6 PALE, and close monitoring of serum sodium levels in high-risk patients for HHV-6 PALE is necessary for immediate diagnosis and treatment initiation.