RESUMEN
Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grades III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1-7) and SR-cGVHD (1-10). The overall response rate was 81.5% (44/54) in SR-aGVHD including 25 complete responses (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3-90.7%, 95% confidence interval (CI)) and 97.4% (92.3-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-reactivation were observed during ruxolitinib treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.
Asunto(s)
Corticoesteroides/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Neoplasias Hematológicas/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Pirazoles/uso terapéutico , Terapia Recuperativa , Adulto , Anciano , Animales , Modelos Animales de Enfermedad , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Quinasas Janus/antagonistas & inhibidores , Masculino , Ratones , Persona de Mediana Edad , Estadificación de Neoplasias , Nitrilos , Pronóstico , Pirimidinas , Recurrencia , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante Homólogo , Adulto JovenRESUMEN
INTRODUCTION: Respiratory syncytial virus (RSV) is a frequent cause of respiratory tract infectious disease (RTID) in allogeneic hematopoietic stem cell transplant (HSCT) recipients associated with a high mortality once infection has progressed from upper RTID (URTID) to lower RTID (URTID). Aerosolized ribavirin (RBV) is considered a cornerstone of treatment, but is expensive and has toxic side effects on patients and staff. In this study, RSV infection was detected by polymerase chain reaction (PCR) from routinely collected throat swabs in HSCT patients. Infected individuals were treated according to an institutional protocol using intravenous (IV) RBV for patients with LRTID and oral ribavirin for URTID. RESULTS: RSV infection was diagnosed in 10 patients (median age 60 years) a median of 15 days after allogeneic HSCT for high-risk acute myeloid leukemia. Five patients with LRTID received IV RBV within 7 days after HSCT, and 5 with URTID were treated with oral RBV 12-40 days after HSCT. One patient died of septic shock associated with Pseudomonas aeruginosa-induced pneumonia 28 days after HSCT in prolonged neutropenia. All patients became RSV PCR negative on throat swabs within a median of 22 days from start of RBV. Despite severe lymphopenia, no patient treated for URTID progressed to LRTID. Neutrophil recovery was delayed in 3 patients. CONCLUSIONS: We show that IV and oral RBV were efficacious in preventing progression and reducing mortality of RSV infection in this small series of allogeneic HSCT recipients. Randomized studies are not to be expected for this condition and therefore reporting case series could help in determining optimal RSV treatment.
