Outcome of Second Allogeneic Hematopoietic Cell Transplantation after Relapse of Myeloid Malignancies following Allogeneic Hematopoietic Cell Transplantation : A Retrospective Cohort on Behalf of the Grupo Español de Trasplante Hematopoyetico

Allogeneic stem cell transplantation (allo-HCT) represents the most effective immunotherapy for acute myeloid leukemia (AML) and myeloid malignancies. However, disease relapse remains the most common cause of treatment failure. By performing a second allo-HCT, durable remission can be achieved in some patients. However, a second allo-HCT is of no benefit for the majority of patients, so this approach requires further understanding. We present a retrospective cohort of 116 patients diagnosed with AML, myelodysplastic syndromes, and myeloproliferative disorders who consecutively underwent a second allo-HCT for disease relapse. The median age was 38 years (range, 4 to 69 years). Sixty-three patients were alive at last follow-up. The median follow-up of the whole cohort was 193 days (range, 2 to 6724 days) and the median follow-up of survivors was 1628 days (range, 52 to 5518 days). Overall survival (OS) at 5 years was 32% (SE ± 4.7%). Multivariate analysis identified active disease status (P <.001) and second allo-HCT < 430 days (the median of the time to second transplantation) after the first transplantation (P <.001) as factors for poor prognosis, whereas the use of an HLA-identical sibling donor for the second allo-HCT was identified as a good prognostic factor (P <.05) for OS. The use of myeloablative conditioning (P =.01), active disease (P =.02), and a donor other than an HLA-identical sibling (others versus HLA-identical siblings) (P =.009) were factors statistically significant for nonrelapse mortality in multivariate analysis. Time to second transplantation was statistically significant (P =.001) in the relapse multivariate analysis, whereas multivariate analysis identified active disease status (P <.001) and time to second transplantation (P <.001) as poor prognosis factors for disease-free survival. This study confirms active disease and early relapse as dismal prognostic factors for a second allo-HCT. Using a different donor at second allo-HCT did not appear to change outcome, but using an HLA-identical sibling donor for a second transplantation appears to be associated with better survival. Further studies are warranted

Does adherence to inhaled corticosteroids predict asthma-related outcomes over time? A cohort study

Inhaled corticosteroids (ICS) adherence is important for asthma management. Current evidence on the impact of ICS adherence on outcomes is mostly based on correlational analyses of between-person data. Although it is widely acknowledged that asthma outcomes fluctuate over time, evidence on predictors of within-person change is scarce. We aimed to quantify these fluctuations and the longitudinal relationships between ICS adherence and outcomes at both between- and within-person levels.A prospective cohort of persistent asthma patients in France and the UK (n=847, age 6-40 years) provided 3756 reports over up to 2 years via computer-assisted telephone interviews and text messages on ICS adherence, asthma control, reliever medication use and exacerbations. We examined adherence-outcome relationships via longitudinal models, controlling for confounders, including severity.Considerable within-person variability was found for exacerbations (91%), asthma control (59%) and reliever use (52%); 431 (11.5%) reports signalled exacerbations and 2046 (54.5%) poor control. At between-person level, patients with higher average adherence were more likely to report asthma control (OR 1.25, 95% CI 1.06-1.47), but not asthma exacerbations (OR 0.99, 95% CI 0.87-1.12) or lower reliever use (b -0.0004, 95% CI -0.089-0.088). At within-person level, higher-than-usual adherence was associated with higher concomitant reliever use (b 0.092, 95% CI 0.053-0.131) and lower subsequent reliever use (b -0.047, 95% CI -0.005- -0.088); it was unrelated to asthma control (OR 0.93, 95% CI 0.84-1.02) or exacerbations (OR 1.04, 95% CI 0.94-1.16).Patients maintaining high ICS adherence over time have better asthma control. Temporarily increasing ICS adherence tends to be simultaneous to higher reliever use and reduces reliever use later on. Causes of within-person variation in outcomes require more investigation

Long-acting beta-agonists plus inhaled corticosteroids safety: a systematic review and meta-analysis of non-randomized studies

Background: Although several systematic reviews investigated the safety of long-acting beta–agonists (LABAs) in asthma, they mainly addressed randomized clinical trials while evidence from non-randomized studies has been mostly neglected. We aim to assess the risk of serious adverse events in adults and children with asthma treated with LABAs and Inhaled Corticosteroids (ICs), compared to patients treated only with ICs, from published non-randomized studies. Methods: The protocol registration number was CRD42012003387 (http://www.crd.york.ac.uk/Prospero webcite). Literature search for articles published since 1990 was performed in MEDLINE and EMBASE. Two authors selected studies independently for inclusion and extracted the data. A third reviewer resolved discrepancies. To assess the risk of serious adverse events, meta-analyses were performed calculating odds ratio summary estimators using random effect models when heterogeneity was found, and fixed effect models otherwise. Results: Of 4,415 candidate articles, 1,759 abstracts were reviewed and 220 articles were fully read. Finally, 19 studies met the inclusion criteria. Most of them were retrospective observational cohorts. Sample sizes varied from 50 to 514,216. The meta-analyses performed (69,939-624,303 participants according to the outcome considered) showed that odds ratio of the LABAs and ICs combined treatment when compared with ICs alone was: 0.88 (95% CI 0.69-1.12) for asthma-related hospitalization; 0.75 (95% CI 0.66-0.84) for asthma-related emergency visits; 1.02 (95% CI 0.94-1.10) for systemic corticosteroids; and 0.95 (95% CI 0.9-1.0) for the combined outcome. Conclusions: Evidence from observational studies shows that the combined treatment of LABAs and ICs is not associated with a higher risk of serious adverse events, compared to ICs alone. Major gaps identified were prospective design, paediatric population and inclusion of mortality as a primary outcome.Financial support for this study was provided by the Health Research Fund (European Union FP7, ASTROLAB project EC HEALTH-F5-2011-282593); the Agency for Management of University and Research Grants AGAUR (2012FI_B1 00177); and a Fundación Carolina Fellowship