ABSTRACT
Chronic graft-versus-host disease (cGVHD) remains a major barrier to successful hematopoietic stem cell transplantation (HSCT). In cases refractory to first-line therapy with steroids, there is no standard of care for second-line therapy. As such, ruxolitinib is a promising drug in this scenario. We retrospectively analyzed the efficacy and safety of ruxolitinib in treating steroid-refractory cGVHD in 35 patients from 2 transplantation centers, with the longest follow-up described to date. The evaluated patients had a median of 3 organs affected (range, 1 to 7 organs), with most (64%) having moderate cGVHD. The median number of previous therapy lines was 2 (range, 1 to 6). The overall response rate was 89% (complete response, 26%) after a median of 4 weeks of therapy. The median follow-up was 43 months (range, 11 to 59 monts). At follow-up, of the 27 patients still alive, 18 (67%) were free of any immunosuppression, and 6 (22%) were receiving ruxolitinib as their sole immunosuppressive drug. Failure-free survival was 77.1% at 6 months, 68.6% at 12 months, 54% at 24 months, and 51.4% at 36 months. The median overall survival was not reached. Toxicities were mostly hematologic and resolved after dosage reduction in most cases. Overall, our data, which represent the cohort of patients with cGVHD treated with ruxolitinib with the longest follow-up to date, support the use of this drug as a safe and effective option for refractory cGVHD.
Subject(s)
Graft vs Host Disease , Follow-Up Studies , Graft vs Host Disease/drug therapy , Humans , Nitriles , Pyrazoles , Pyrimidines , Retrospective Studies , SteroidsABSTRACT
BACKGROUND: Malnutrition is a common finding in allogeneic hematopoietic stem cell transplantation (alloHSCT) patients, and there is some evidence that malnutrition might negatively affect the transplant outcomes. METHOD: We performed a retrospective study with 148 patients aged 18-75 years, who underwent alloHSCT between 2011 and 2017. Patients were classified according to the body mass index (BMI) and the Subjective Global Assessment (SGA). The SGA was assessed on the day of hospitalization for the transplant, and classifies patients into three groups: A (well-nourished), B (moderately malnourished) and C (severely malnourished). RESULTS: The SGA classified 49 (33%) patients as well-nourished, 54 (37%) as moderately malnourished, and 45 (30%) as severely malnourished. SGA-C was also associated with severe acute graft versus host disease (aGVHD) with a cumulative incidence (CI) of 31% vs. a CI of 14% for combined well-nourished or moderately malnourished group (SGA-A or -B, P = 0.017). In multivariate analysis, SGA-C compared to SGA-A or -B, remained as an independent risk factor for aGVHD (hazard ratio - HR 1.68, 95% confidence interval - 95% CI 1.02-2.74), and nonrelapse mortality (NRM - HR 3.63, 95% CI 1.76-7.46), worse progression free survival (HR 2.12, 95% CI 1.25-3.60), and worse overall survival (HR 3.27, 95% CI 1.90-5.64). CONCLUSION: Malnutrition increases the risk of aGVHD and NRM and has a negative impact on survival.
Subject(s)
Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation , Malnutrition/complications , Adolescent , Adult , Aged , Body Mass Index , Brazil , Female , Hospitalization , Humans , Incidence , Male , Middle Aged , Multivariate Analysis , Nutritional Status , Proportional Hazards Models , Retrospective Studies , Risk Factors , Survival Analysis , Treatment Outcome , Young AdultSubject(s)
Graft vs Host Disease/drug therapy , Pyrazoles/therapeutic use , Salvage Therapy/methods , Adrenal Cortex Hormones/pharmacology , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Brazil , Chronic Disease , Female , Humans , Male , Middle Aged , Nitriles , Pyrazoles/adverse effects , Pyrimidines , Remission Induction/methods , Salvage Therapy/adverse effects , Treatment Outcome , Young AdultABSTRACT
As anormalidades do desenvolvimento pulmonar são classificadas em três grupos a saber: hipoplasia, aplasia e agenesia pulmonares. A incidência destas anormalidades é baixa e não há predominância por sexo nem idade. Estão associadas a anormalidades cardíacas, sendo as mais freqüentes o ductus arterioso e forame oval. Outras anormalidades como malformações ósseas, gastrointestinais (cisto hepáticos, hérnia diafragmática), urogenitais (agenesia renal), agenesia diafragmática e do sistema nervoso central podem ocorrer excepcionalmente. A apresentação clínica é muito variável, podendo se apresentar de forma assintomática, sendo a infecção brônquica de repetição a apresentação mais freqüente. Em algumas situações o diagnóstico de doença pulmonar é suspeitado pelo achado radiológico em paciente assintomático, enquanto outros se apresentam com quadro respiratório grave. A tomografia computadorizada de tórax (TC) é o método diagnóstico de eleição, sendo os achados mais freqüentes a opacidade homogênea unilateral com interrupção abrupta do brônquio fonte, desvio do mediastino ipsilateral e sinais de vicariância do pulmão contralateral
Subject(s)
Humans , Young Adult , Lung/abnormalities , RadiologyABSTRACT
As anormalidades do desenvolvimento pulmonar são classificadas em três grupos a saber: hipoplasia, aplasia e agenesia pulmonares. A incidência destas anormalidades é baixa e não há predominância por sexo nem idade. Estão associadas a anormalidades cardíacas, sendo as mais freqüentes o ductus arterioso e forame oval. Outras anormalidades como malformações ósseas, gastrointestinais (cisto hepáticos, hérnia diafragmática), urogenitais (agenesia renal), agenesia diafragmática e do sistema nervoso central podem ocorrer excepcionalmente. A apresentação clínica é muito variável, podendo se apresentar de forma assintomática, sendo a infecção brônquica de repetição a apresentação mais freqüente. Em algumas situações o diagnóstico de doença pulmonar é suspeitado pelo achado radiológico em paciente assintomático, enquanto outros se apresentam com quadro respiratório grave. A tomografia computadorizada de tórax (TC) é o método diagnóstico de eleição, sendo os achados mais freqüentes a opacidade homogênea unilateral com interrupção abrupta do brônquio fonte, desvio do mediastino ipsilateral e sinais de vicariância do pulmão contralateral
