Data Availability StatementThe datasets presented in this article are not readily available because of the EBMT regulations. lower HCE as % of Gross Domestic Product per capita (= 0.003) and lower values of the Human Development Index (= 0.02). In a multivariate model, the risk of TRM was most strongly predicted by current HCE (HR = 0.76, = 0.006). HCE median was also associated with reduced risk of the overall mortality (HR 0.73, = 0.0006) and reduced risk of treatment failure (either relapse or Isoacteoside TRM; HR 0.77, = 0.004). We conclude that country-specific socioeconomic factors, in particular current HCE, are strongly associated with survival of patients who experience severe aGvHD. T-cell depletion, use of Isoacteoside TBI). In order to take non-independence of data within a country into account, a Isoacteoside random effect or frailty was introduced for each country into the models (12, 13). A frailty is usually a latent random effect that enters multiplicatively around the hazard function. The median follow-up for survivors was 29 months. All tests were two-sided with type I error rate fixed at 0.05. Statistical analyses were performed with SPSS 24.0 (IBM Corp., Armonk, NY, USA) and R 3.4.2 (R Core Team (2017). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/). Results Patients, Donors, and HCT Procedure Altogether 4,152 patients, including 2,573 men, treated with alloHCT from either MSD (= 1,328, 32%) or URD (= 2,824, 68%) in 282 transplant centers located in 30 European countries were included in the analysis. Median age was 53 years (range, 18C79 years). Acute leukemias were the most frequent indication for transplantation (= 2,091, 50%), followed by myelodysplastic syndromes and myeloproliferative neoplasms (= 884, 21%). Peripheral blood was the predominant source of stem cells (= 3,796, 91%). The conditioning regimens were myeloablative or reduced intensity, in almost equal proportions. Detailed patients and procedure characteristics are listed in Table 1. Transplant-Related Mortality The TRM rates at 6, 12, and 24 months for the whole group were 41% (95%CI: 39C42), 51% (49C52), and 56% (54C57), respectively. The most frequent causes of TRM Rabbit Polyclonal to CATZ (Cleaved-Leu62) were: GvHD (74.8%), infections (19%), veno-occlusive disease (2.3%), interstitial pneumonitis (1.2%), and hemorrhage (1%). However, in 223 out of 2,324 (5.3%) cases the cause of death was reported as other or unknown. In a univariate analysis, the probability of TRM at 2 years was increased for countries with lower current HCE (median vs. median, 61 vs. 55%, respectively, = 0.04), lower HCE as % of Gross Domestic Product (GDP) (60 vs. 54%, = 0.003), and lower values of HDI (59 vs. 55%, = 0.02) (Table 2, Physique 1). In a multivariate analysis, the strongest effect was observed where current HCE was included in the model (hazard ratio, HR = 0.76, 95%CI, 0.62C0.92; = 0.006). Significant associations were also observed for models including HCE as % of GDP and HDI (Table 3). No significant associations were found between TRM and team density or individual team activity. Table 2 Results of the univariate analysis of associations of economic and socioeconomic factors with outcome. = 0.03) (Table 3). Progression-Free Survival and Overall Survival The PFS and OS rates at 2 years were 29% (95%CI: 27C30) and 31% (95%CI: 29C33), respectively. Among 2,691 patients who died, the causes of death were assessed Isoacteoside as transplant-related in 2,090 (78%) cases, disease-related in 408 (15%) cases while other or unknown in remaining 194 (7%) cases. In a univariate analysis, the probability of PFS at 2 years was increased for countries with higher current HCE ( median vs. median, 29 vs. 22%, respectively, = 0.01), higher HCE as % of Gross Domestic Product (GDP) (30 vs. 23%, 0.001), and higher values of HDI (30 vs. 23%, = 0.001) (Table 2, Physique 2). The same factors were identified to influence the risk of treatment failure (either progression or death without progression, inverse PFS) in a multivariate model (Table 3). The strongest association was found for HCE as % of GDP Isoacteoside (HR = 0.78, 95%CI, 0.68C0.90; = 0.0006). Open in a separate window Physique 2 Association of Health Care Expenditure as % of Gross Domestic.