Impact of FLT3 Internal Tandem Duplication on the Outcome of Related and Unrelated Hematopoietic Transplantation for Adult Acute Myeloid Leukemia in First Remission: A Retrospective Analysis

Purpose Patients with acute myeloid leukemia (AML) and FLT3/internal tandem duplication (FLT3/ITD) have poor prognosis if treated with chemotherapy only. Whether this alteration also affects outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) remains uncertain. Patients and Methods We analyzed 206 patients who underwent HLA-identical sibling and matched unrelated HSCTs reported to the European Group for Blood and Marrow Transplantation with a diagnosis of AML with normal cytogenetics and data on FLT3/ITD (present: n = 120, 58%; absent: n = 86, 42%). Transplantations were performed in first complete remission (CR) after myeloablative conditioning. Results Compared with FLT3/ITD-negative patients, FLT3/ITD-positive patients had higher median leukocyte count at diagnosis (59 v 21 x 10(9)/L; P < .001) and shorter interval from CR to transplantation (87 v 99 days; P = .04). Other characteristics were similar in the two groups. At 2 years, relapse incidence (RI; +/- standard deviation) was higher (30% +/- 5% v 16% +/- 5%; P = .006) and leukemia-free survival (LFS) lower (58% +/- 5% v 71% +/- 6%; P = .04) in FLT3/ITD-positive compared with FLT3/ITD-negative patients. In multivariate analyses, FLT3/ITD led to increased RI (hazard ratio [HR], 3.4; 95% CI, 1.46 to 7.94; P = .005), as did older age, female sex, shorter interval between CR and transplantation, and higher number of chemotherapy courses before achieving CR. FLT3/ITD positivity was associated with decreased LFS (HR, 0.37; 95% CI, 0.19 to 0.73; P = .002), along with older age and higher number of chemotherapy courses before achieving CR. Conclusion FLT3/ITD adversely affected the outcome of HSCT in the same direction it does after chemotherapy; despite this, more than half of the patients harboring this mutation who received transplants were alive and leukemia free at 2 years. To further improve the results, use of FLT3 inhibitors before or after HSCT deserves investigation.

Do charges to freight trucks and trains in the European Union reflect their social marginal costs? Application to the case of Spain

In the last few years, the European Union (EU) has become greatly concerned about the environmental costs of road transport in Europe as a result of the constant growth in the market share of trucks and the steady decline in the market share of railroads. In order to reverse this trend, the EU is promoting the implementation of additional charges for heavy goods vehicles (HGV) on the trunk roads of the EU countries. However, the EU policy is being criticised because it does not address the implementation of charges to internalise the external costs produced by automobiles and other transport modes such as railroad. In this paper, we first describe the evolution of the HGV charging policy in the EU, and then assess its practical implementation across different European countries. Second, and of greater significance, by using the case study of Spain, we evaluate to what extent the current fees on trucks and trains reflect their social marginal costs, and consequently lead to an allocative-efficient outcome. We found that for the average case in Spain the truck industry meets more of the marginal social cost produced by it than does the freight railroad industry. The reason for this lies in the large sums of money paid by truck companies in fuel taxes, and the subsidies that continue to be granted by the government to the railroads.