The daily market for funds in Europe: what has changed with the EMU?

This paper presents evidence that the existence of deposit and lending facilities combined with an averaging provision for the reserve requirement are powerful tools to stabilize the overnight rate. We reach this conclusion by comparing the behavior of this rate in Germany before and after the start of the EMU. The analysis of the German experience is useful because it allows to isolate the effects on the overnight rate of these particular instruments of monetary policy. To show that this outcome is a general conclusion and not a particular result of the German market, we develop a theoretical model of reserve management which is able to reproduce our empirical findings.

Toxoplasmose congênita

We had the opportunity to study 6 cases of the congenital form of toxoplasmosis, found in a series of 1200 necropsies of fetuses and newborn babies, realized at 3 different hospitals in Rio de Janeiro, Brazil. Among the 6 cases, 4 were premature babies liveborn at the 6th-8th gestational month and 2 were stillborn (1 premature and 1 at term). In all those cases, the diagnosis was based in the detection of the parasite in tissues and in one case it was even isolated the Toxoplasma from the necrotic material found in the cranial cavity. This strain of Toxoplasma, pathogenic to pigeons, to guinea pigs and to mice, is preserved by successive transfers in mice. Some facts observed in those cases present an interest not only strictly anatomic but also have certain value for the better acknowlegment of the disease. First, we want to call the attention to the presence of a sudden high fever, during or just before pregnancy in the 4 cases in which the maternal anamnesis was perfectly studied; this fever that was preceded by a normal beginning of pregnancy, had relatively rapid remission, but in 2 cases was immediately followed by uterine bleeding and premature delivery, although the puerperium had been apparently normal. It is known that are normal the subsequent children of the mothers that delivered a baby with toxoplasmosis and that several women have normal babies before the toxoplasmotic one. We believe that the fever observed in our cases could be indicative of the beginning of maternal infection and those are the reasons why we emphasize the need of careful anamnesis, specially in the cases actually diagnosed as inapparent infection. Another fact to notice is that in 5 of our cases the event premature delivery happened always between the 6th and the 8th months of pregnancy, and the only term fetus was delivered in advanced stage of maceration. The above mentioned facts could agree with the opinion of FRENKEL (1949), when he declared that "primary infection of the pregnant mother appears more likely to be the commoner mode of fetal toxoplasmic infection", but they would disagree with WEINMAN (1952) who believes that the transmission of Toxoplasma to the fetus is more frequent through a pregnant woman with chronic disease and who says "that infection contracted during pregnancy may and probably does happen from time to time"...Still in connection with the transmission of toxoplasmosis, we want to note the verification of inflammatory lesions in the placental villi and in the umbilical cord in 3 of the 4 cases in which such organs were examined at the microscope. In the case n. 1, we found several pseudocysts of Toxoplasma in the placenta, and the fibroblasts of Wharton's jelly were particularly rich in isolated forms and in colonies of Toxoplasma; the easy multiplication of the parasite in that tissue calls the attention and even suggests its utilisation for Toxoplasma's cultivation. The confirmation of Toxoplasma in human placenta was made only recently by CRISTEN et al. (1951) and by NEGHME et al. (1952), in Chile; it is not frequent in the literature, what gives some value to our present verification. Another observation was that provided by the case n. 6. This baby, a premature one of the 6th month, was 14 days old and-died with signs of respiratory disease, the causa mortis have been pneumonia. At the necropsy, we found no gross change that suggested toxoplasmosis, except the presence of some small necrotic focuses in the cerebral nervous substance around the ventricles. As a matter of fact, there was no enlargement of spleen or liver and neither leptomeningitis nor hydrocephalus. Such focuses were attributed to possible anoxia and in fact they are extremely similar to anoxial softenings, even when they are examined at the microscope; its structure composed of a central necrotic zone, surrounded by proliferated neuroglia and by a variable deposit of calcium salts, closely simulated the anoxial softenings, when the microscopical examination is based in the common histological preparations (hematoxilin-eosin, etc.). But when we examine preparations by the Giemsa or by the periodic acid-Schiff methods, we will note the presence of Toxoplasma, with its typical aspect or a little changed by degeneration. When we describe this observation, we wish to evidence the need of the search of Toxoplasma and closed parasites, in the cases of supposed pure anoxial softenings of nervous substance, in children. The frequency with which the congenital toxoplasmosis was anatomically verified should be emphasized, although the disease had not been clinically suspected, and it should be borne in mind that the second case of toxoplasmosis reported in the world was observed in Brazil by MAGARINOS TORRES; this case was the first to be described of the generalized congenital form of the infection, i. e. with myocardial lesions and parasites in skeletal muscles and skin.

Pla de gestió i conservació dels Estanyets de Pals i les Closes Fondes (Pals, Baix Empordà)

Es destaca la presència de tres espècies bioinvasores, tals com la gambúsia(Gambusiaaffinis), la canya (Arundodonax) i el cranc vermell americà (Procambarusclarkii). S’ha detectat que la qualitat de l’aigua ha disminuït en alguns paràmetres, especialment en l’Estanyet del Safareig. En els tres estanyets els sòlids dissolts totalsa TSD) estan al voltant del límit màxim recomanat per la EPA (Agència de Protecció Ambiental d’Estats Units). S’ha observat que la Cladophora, indicadora de concentracions elevades de nitrogen a l’aigua, és un cloròfit molt abundant. S’han identificat dos hàbitats d’interès comunitari no prioritari, segons la Directiva Hàbitats: les closes i les freixenedes termòfiles de Fraxinusangustifolia. En funció dels resultats obtinguts s’han elaborat les propostes de gestió i conservació per aquest espai.

Results of An International Study of Quantitative BCR/ABL Assays Using Defined RNA Samples

Molecular monitoring of BCR/ABL transcripts by real time quantitative reverse transcription PCR (qRT-PCR) is an essential technique for clinical management of patients with BCR/ABL-positive CML and ALL. Though quantitative BCR/ABL assays are performed in hundreds of laboratories worldwide, results among these laboratories cannot be reliably compared due to heterogeneity in test methods, data analysis, reporting, and lack of quantitative standards. Recent efforts towards standardization have been limited in scope. Aliquots of RNA were sent to clinical test centers worldwide in order to evaluate methods and reporting for e1a2, b2a2, and b3a2 transcript levels using their own qRT-PCR assays. Total RNA was isolated from tissue culture cells that expressed each of the different BCR/ABL transcripts. Serial log dilutions were prepared, ranging from 100 to 10-5, in RNA isolated from HL60 cells. Laboratories performed 5 independent qRT-PCR reactions for each sample type at each dilution. In addition, 15 qRT-PCR reactions of the 10-3 b3a2 RNA dilution were run to assess reproducibility within and between laboratories. Participants were asked to run the samples following their standard protocols and to report cycle threshold (Ct), quantitative values for BCR/ABL and housekeeping genes, and ratios of BCR/ABL to housekeeping genes for each sample RNA. Thirty-seven (n=37) participants have submitted qRT-PCR results for analysis (36, 37, and 34 labs generated data for b2a2, b3a2, and e1a2, respectively). The limit of detection for this study was defined as the lowest dilution that a Ct value could be detected for all 5 replicates. For b2a2, 15, 16, 4, and 1 lab(s) showed a limit of detection at the 10-5, 10-4, 10-3, and 10-2 dilutions, respectively. For b3a2, 20, 13, and 4 labs showed a limit of detection at the 10-5, 10-4, and 10-3 dilutions, respectively. For e1a2, 10, 21, 2, and 1 lab(s) showed a limit of detection at the 10-5, 10-4, 10-3, and 10-2 dilutions, respectively. Log %BCR/ABL ratio values provided a method for comparing results between the different laboratories for each BCR/ABL dilution series. Linear regression analysis revealed concordance among the majority of participant data over the 10-1 to 10-4 dilutions. The overall slope values showed comparable results among the majority of b2a2 (mean=0.939; median=0.9627; range (0.399 - 1.1872)), b3a2 (mean=0.925; median=0.922; range (0.625 - 1.140)), and e1a2 (mean=0.897; median=0.909; range (0.5174 - 1.138)) laboratory results (Fig. 1-3)). Thirty-four (n=34) out of the 37 laboratories reported Ct values for all 15 replicates and only those with a complete data set were included in the inter-lab calculations. Eleven laboratories either did not report their copy number data or used other reporting units such as nanograms or cell numbers; therefore, only 26 laboratories were included in the overall analysis of copy numbers. The median copy number was 348.4, with a range from 15.6 to 547,000 copies (approximately a 4.5 log difference); the median intra-lab %CV was 19.2% with a range from 4.2% to 82.6%. While our international performance evaluation using serially diluted RNA samples has reinforced the fact that heterogeneity exists among clinical laboratories, it has also demonstrated that performance within a laboratory is overall very consistent. Accordingly, the availability of defined BCR/ABL RNAs may facilitate the validation of all phases of quantitative BCR/ABL analysis and may be extremely useful as a tool for monitoring assay performance. Ongoing analyses of these materials, along with the development of additional control materials, may solidify consensus around their application in routine laboratory testing and possible integration in worldwide efforts to standardize quantitative BCR/ABL testing.

Y-90-Ibritumomab Tiuxetan (Zevalin (R)) Consolidation of First Remission In Advanced-Stage Follicular Non-Hodgkin's Lymphoma: Updated Results After a Median Follow-up of 66.2 Months From the International, Randomized, Phase III First-Line Indolent Trial (FIT) In 414 Patients

The FIT trial was conducted to evaluate the safety and efficacy of 90Y-ibritumomab tiuxetan (0.4 mCi/kg; maximum dose 32 mCi) when used as consolidation of first complete or partial remission in patients with previously untreated, advanced-stage follicular lymphoma (FL). Patients were randomly assigned to either 90Y-ibritumomab treatment (n = 207) or observation (n = 202) within 3 months (mo) of completing initial induction therapy (chemotherapy only: 86%; rituximab in combination with chemotherapy: 14%). Response status prior to randomization did not differ between the groups: 52% complete response (CR)/CR unconfirmed (CRu) to induction therapy and 48% partial response (PR) in the 90Y-ibritumomab arm vs 53% CR/CRu and 44% PR in the control arm. The primary endpoint was progression-free survival (PFS) of the intent-to-treat (ITT) population. Results from the first extended follow-up after a median of 3.5 years revealed a significant improvement in PFS from the time of randomization with 90Y-ibritumomab consolidation compared with control (36.5 vs 13.3 mo, respectively; P < 0.0001; Morschhauser et al. JCO. 2008; 26:5156-5164). Here we report a median follow-up of 66.2 mo (5.5 years). Five-year PFS was 47% in the 90Y-ibritumomab group and 29% in the control group (hazard ratio (HR) = 0.51, 95% CI 0.39-0.65; P < 0.0001). Median PFS in the 90Y-ibritumomab group was 49 mo vs 14 mo in the control group. In patients achieving a CR/CRu after induction, 5-year PFS was 57% in the 90Y-ibritumomab group, and the median had not yet been reached at 92 months, compared with a 43% 5-year PFS in the control group and a median of 31 mo (HR = 0.61, 95% CI 0.42-0.89). For patients in PR after induction, the 5-year PFS was 38% in the 90Y-ibritumomab group with a median PFS of 30 mo vs 14% in the control group with a median PFS of 6 mo (HR = 0.38, 95% CI 0.27-0.53). Patients who had received rituximab as part of induction treatment had a 5-year PFS of 64% in the 90Y-ibritumomab group and 48% in the control group (HR = 0.66, 95% CI 0.30-1.47). For all patients, time to next treatment (as calculated from the date of randomization) differed significantly between both groups; median not reached at 99 mo in the 90Y-ibritumomab group vs 35 mo in the control group (P < 0.0001). The majority of patients received rituximab-containing regimens when treated after progression (63/82 [77%] in the 90Y-ibritumomab group and 102/122 [84%] in the control group). Overall response rate to second-line treatment was 79% in the 90Y-ibritumomab group (57% CR/CRu and 22% PR) vs 78% in the control arm (59% CR/CRu, 19% PR). Five-year overall survival was not significantly different between the groups; 93% and 89% in the 90Y-ibritumomab and control groups, respectively (P = 0.561). To date, 40 patients have died; 18 in the 90Y-ibritumomab group and 22 in the control group. Secondary malignancies were diagnosed in 16 patients in the 90Y-ibritumomab arm vs 9 patients in the control arm (P = 0.19). There were 6 (3%) cases of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) in the 90Y-ibritumomab arm vs 1 MDS in the control arm (P = 0.063). In conclusion, this extended follow-up of the FIT trial confirms the benefit of 90Y-ibritumomab consolidation with a nearly 3 year advantage in median PFS. A significant 5-year PFS improvement was confirmed for patients with a CR/CRu or a PR after induction. Effective rescue treatment with rituximab-containing regimens may explain the observed no difference in overall survival between both patient groups who were - for the greater part - rituximab-naïve.

Stable hydrogen and oxygen isotope composition of waters from mine tailings in different climatic environments

The stable isotope composition of waters (delta H-2, delta O-18) can be used as a natural tracer of hydrologic processes in systems affected by acid mine drainage. We investigated the delta H-2 and delta O-18 values of pore waters from four oxidizing sulfidic mine tailings impoundments in different climatic regions of Chile (Piuquenes at La Andina with Alpine climate, Cauquenes and Caren at El Teniente with Mediterranean climate, and Talabre at the Chuquicamata deposit with hyperarid climate). No clear relationship was found between altitude and isotopic composition. The observed displacement of the tailings pore waters from the local meteoric water line toward higher delta O-18 values (by similar to +2% delta O-18 relative to delta H-2) is partly due to water-rock interaction processes, including hydration and O-isotope exchange with sulfates and Fe(III) oxyhydroxides produced by pyrite oxidation. In most tailings, from the saturated zone toward the surface, isotopically different zones can be distinguished. Zone I is characterized by an upward depletion of H-2 and O-18 in the pore waters from the saturated zone and the lowermost vadose zone, due to ascending diffused isotopically light water triggered by the constant loss of water vapor by evaporation at the surface. In zone II, the capillary flow of a mix of vapor and liquid water causes an evaporative isotopic enrichment in H-2 and O-18. At the top of the tailings in dry climate a zone III between the capillary zone and the surface contains isotopically light diffused and atmospheric water vapor. In temperate climates, the upper part of the profile is affected by recent rainfall and zone III may not differ isotopically from zone II.

On the Relationship between Market Power and Bank Risk Taking

We analyse risk-taking behaviour of banks in the context of spatial competition. Banks mobilise unsecured deposits by offering deposit rates, which they invest either in a prudent or a gambling asset. Limited liability along with high return of a successful gamble induce moral hazard at the bank level. We show that when the market power is low, banks invest in the gambling asset. On the other hand, for sufficiently high levels of market power, all banks choose the prudent asset to invest in. We further show that a merger of two neighboring banks increases the likelihood of prudent behaviour. Finally, introduction of a deposit insurance scheme exacerbates banks’ moral hazard problem.

Geochemistry of highly acidic mine water following disposal into a natural lake with carbonate bedrock

Acid mine drainage (AMD) from the Zn-Pb(-Ag-Bi-Cu) deposit of Cerro de Pasco (Central Peru) and waste water from a Cu-extraction plant has been discharged since 1981 into Lake Yanamate, a natural lake with carbonate bedrock. The lake has developed a highly acidic pH of similar to 1. Mean lake water chemistry was characterized by 16,775 mg/L acidity as CaCO(3), 4330 mg/L Fe and 29,250 mg/L SO(4). Mean trace element concentrations were 86.8 mg/L Cu, 493 mg/L Zn, 2.9 mg/L Pb and 48 mg/L As, which did not differ greatly from the discharged AMD. Most elements showed increasing concentrations from the surface to the lake bottom at a maximal depth of 41 m (e.g. from 3581 to 5433 mg/L Fe and 25,609 to 35,959 mg/L SO(4)). The variations in the H and 0 isotope compositions and the element concentrations within the upper 10 m of the water column suggest mixing with recently discharged AMD, shallow groundwater and precipitation waters. Below 15 m a stagnant zone had developed. Gypsum (saturation index, SI similar to 0.25) and anglesite (SI similar to 0.1) were in equilibrium with lake water. Jarosite was oversaturated (SI similar to 1.7) in the upper part of the water column, resulting in downward settling and re-dissolution in the lower part of the water column (SI similar to -0.7). Accordingly, jarosite was only found in sediments from less than 7 m water depth. At the lake bottom, a layer of gel-like material (similar to 90 wt.% water) of pH similar to 1 with a total organic C content of up to 4.40 wet wt.% originated from the kerosene discharge of the Cu-extraction plant and had contaminant element concentrations similar to the lake water. Below the organic layer followed a layer of gypsum with pH 1.5, which overlaid the dissolving carbonate sediments of pH 5.3-7. In these two layers the contaminant elements were enriched compared to lake water in the sequence As < Pb approximate to Cu < Cd < Zn = Mn with increasing depth. This sequence of enrichment was explained by the following processes: (i) adsorption of As on Fe-hydroxides coating plant roots at low pH (up to 3326 mg/kg As), (ii) adsorption at increasing pH near the gypsum/calcite boundary (up to 1812 mg/kg Pb, 2531 mg/kg Cu. and 36 mg/kg Cd), and (iii) precipitation of carbonates (up to 5177 mg/kg Zn and 810 mg/kg Mn: all data corrected to a wet base). The infiltration rate was approximately equal to the discharge rate, thus gypsum and hydroxide precipitation had not resulted in complete clogging of the lake bedrocks. (C) 2010 Elsevier Ltd. All rights reserved.

Asymmetric standing facilities: an unexploited monetary policy tool

This paper analyzes the role of standing facilities in the determination of the demand for reserves in the overnight money market. In particular, we study how the asymmetric nature of the deposit and lending facilities could be used as a powerful policy tool for the simultaneous control of prices and quantities in the market for daily funds.

Egg-laying induced by insemination in Biomphalaria snails

Contrasting with many populations of Biomphalaria glabrata and B. straminea previously dealt with in this laboratory, which when reared in isolation deposit self-fertilized eggs without apparent restraint, isolated individuals of the former species from São Sebastião do Passé, Bahia state, and of the latter from Porto Alegre, Rio Grande do Sul state, show a high degree of self-sterility, laying egg capsules with a few usually abortive, rarely viable egg cells, or just jellylike masses without egg cells. When two individuals are paired they readily copulate, usually withing 24 hr deposit one of more egg capsules containing many eggs, and egg-laying continues up to exhaustion of stored allosperm. So far this aspect of reproductive biology has been only observed in a number of populations of the planorbid species Helisoma duryi, and should be viewed as a populational rather than specific characteristic. Since sterility is not overcome by courtship, copulation and insemination by individuals of a different species, the stimulating factor that causes ovulation in the studied self-sterile individuals is considered to be present in the conspecific allosperm.

SWORD : utilitat per a la integració de repositoris amb aplicacions de gestió docent

A la Universitat Politècnica de Catalunya (UPC) el procés de gestió de les memòries dels projectes de final de carrera i màster està en funció del model organitzatiu de cada escola o facultat. Aquest escenari implica diferents fluxos de treball i de temps per al dipòsit d'aquestes memòries en el repositori del portal d'accés obert al coneixement UPCommons (www.upcommons.edu) Amb la voluntat de no incidir en aquests processos de cada escola o facultat, s'ha desenvolupat amb la Facultat d'Informàtica de Barcelona (FIB) un sistema d'integració de les memòries i les seves dades associats de forma transparent durant el procés administratiu per mitjà d'uns connectors desenvolupats conjuntament pel servei de Biblioteques de la UPC i el laboratori de càlcul de la FIB. Aquests connectors es basen en la tecnologia SWORD (Simple Web-services Offering Repository Deposit) que per mitjà de XML codifiquen les dades introduïdes i els pre-bolquen en el dipòsit de treballs acadèmics abans de la lectura de la memòria.

Three Generation Family With Pattern Dystrophy and a Successful Treatment of Subfoveal Cnv Related to Pattern Dystrophy With Anti-vegf Intravitreal Injections

Purpose: To phenotype a large 3 generation Swiss family with pattern dystrophy and to report a successful result of treatment with ranibizumab of a subfoveal choroidal neovascularisation (CNV) associated with pattern dystrophy in 1 patient Patients and methods: 4 affected and 3 unaffected patients (3 female 4 male, age range: 19 - 80 years) were assessed with a complete ophthalmologic examination. AF images were taken using Heidelberg Retina Angiograph and the digital color photos, fluorescein angiogragraphy (FFA) using the same TOPCON 501 camera. Electroretinogram (full-field and multifocal) was performed in 1 affected patient. One 48 years old patient developed a subfoveal CNV, which was treated with 2 injections of ranibizumab, at 3 months interval. Blood sample was taken for molecular analysis (screening of the gene RDS). Results: Two patients had a typical fundoscopic appearance of pattern dystrophy with butterfly shaped deposit at the fovea and some peripheral flecks, as shown with AF imaging.. Two others affected patients had a more unusual appearance with some macular atrophy in one or both eyes, surrounded by flecks. The visual acuity ranged from 1.0 to 0.1 according to Snellen EDTRS chart. The patient with subfoveal CNV presented a drop of vision form 1.0 to 0.6 within 10 days prior to the diagnosis and also reported some metamorphopsia. FFA and optical computerized tomography (OCT) confirmed a classic CNV. After the 1st injection her vision improved to 1.0 but persistent metamorphopsia and fluid on OCT motivated a second injection. One month after the second injection the OCT was flat and the patient had no symptoms. The results of RDS screening will be presented at the meeting. Conclusion: We present a family with pattern dystrophy, with some members having an unusual fundus appearance, which was mistaken for an early onset dry AMD. The AF imaging is a useful tool in diagnosing this condition. A CNV associated with pattern dystrophy a rare. This is the first report of a successful treatment of the CNV with anti-VEGF intravitreal injections.

Hydrocarbon biomarkers in the Topla-Mezica zinc-lead deposits, northern Karavanke/Drau Range, Slovenia: Paleoenvironment at the site of ore formation

The Mississippi Valley-type zinc and lead deposits at Topla (250,150 metric tons (t) of ore grading 1.0 wt % Zn and 3.3 wt % Pb) and Mezica (19 million metric tons (Mt) of ore grading 5.3 wt % Pb and 2.7 wt % Zn) occur within the Middle to Upper Triassic platform carbonate rocks of the northern Karavanke/Drau Range geotectonic units of the Eastern Alps, Slovenia. The ore and host rocks of these deposits have been investigated by a combination of inorganic and organic geochemical methods to determine major, trace, and rare earth element (REE) concentrations, hydrocarbon distribution, and stable isotope ratios of carbonates, kerogen, extractable organic matter, and individual hydrocarbons. These data combined with sedimentological evidence provide insight into the paleoenvironmental conditions at the site of ore formation. The carbonate isotope composition, the REE patterns, and the distribution of hydrocarbon biomarkers (normal alkanes and steranes) suggest a marine depositional environment. At Topla, a relatively high concentration of redox sensitive trace elements (V, Mo, U) in the host dolostones and REE patterns parallel to that of the North American shale composite suggest that sediments were deposited in a reducing environment. Anoxic conditions enhanced the preservation of organic matter and resulted in relatively higher total organic carbon contents (up to 0.4 wt %). The isotopic composition of the kerogen (delta C-13(kerogon) = -29.4 to -25.0 parts per thousand, delta N-15(kerogen) = -.13.6 to 6.8 parts per thousand) suggests that marine algae and/or bacteria were the main source of organic carbon with a very minor contribution from detrital continental plants and a varying degree of alteration. Extractable organic matter from Topla ore is generally depleted in C-13 compared to the associated kerogen, which is consistent with an indigenous source of the bitumens. The mineralization correlates with delta N-15(kerogen) values around 0 per mil, C-13 depleted kerogen, C-13 enriched n-heptadecane, and relatively high concentrations of bacteria] hydrocarbon biomarkers, indicating a high cyanobacterial biomass at the site of ore formation. Abundant dissimilatory sulfate-reducing bacteria, feeding on the cyanobacterial remains, led to accumulation of biogenic H2S in the pore water of the sediments. This biogenic H2S was mainly incorporated into sedimentary organic matter and diagenetic pyrite. Higher bacterial activity at the ore site also is indicated by specific concentration ratios of hydrocarbons, which are roughly correlated with total Pb plus Zn contents. This correlation is consistent with mixing of hydrothermal metal-rich, fluids and local bacteriogenic sulfide sulfur. The new geochemical data provide supporting evidence that Topla is a low-temperature Mississippi Valley-type deposit formed in an anoxic supratidal saline to hypersaline environment. A laminated cyanobacterial mat, with abundant sulfate-reducing bacteria was the main site of sulfate reduction.

Autologous Stem Cell Transplantation (ASCT) for Enteropathy-Associated T-Cell Lymphoma (EATL): Final Analysis of a Retrospective Study On the Behalf of Lymphoma Working Party (LWP) of the European Group for Blood and Marrow Transplantation (EBMT).

Background: EATL is a rare subtype of peripheral T-cell lymphomas characterized by primarily intestinal localization and a frequent association with celiac disease. The prognosis is considered to be poor with conventional chemotherapy. Limited data is available on the efficacy of ASCT in this lymphoma subtype. Primary objective: was to study the outcome of ASCT as a consolidation or salvage strategy for EATL. The primary endpoint was overall survival (OS) and progression-free survival (PFS). Eligible patients were > 18 years who had received ASCT between 2000-2010 for EATL that was confirmed by review of written histopathology reports, and had sufficient information on disease history and follow-up available. The search strategy used the EBMT database to identify patients potentially fulfilling the eligibility criteria. An additional questionnaire was sent to individual transplant centres to confirm histological diagnosis (histopathology report or pathology review) as well as updated follow-up data. Patients and transplant characteristics were compared between groups using X2 test or Fisher's exact test for categorical variables and t-test or Mann-Whiney U-test for continuous variables. OS and PFS were estimated using the Kaplan-Meier product-limit estimate and compared by the log-rank test. Estimates for non-relapse mortality (NRM) and relapse or progression were calculated using cumulative incidence rates to accommodate competing risk and compared to Gray's test. Results: Altogether 138 patients were identified. Updated follow-up data was received from 74 patients (54 %) and histology report from 54 patients (39 %). In ten patients the diagnosis of EATL could not be adequately verified. Thus the final analysis included 44. There were 24 males and 20 females with a median age of 56 (35-72) years at the time of transplant. Twenty-five patients (57 %) had a history of celiac disease. Disease stage was I in nine patients (21 %), II in 14 patients (33 %) and IV in 19 patients (45 %). Twenty-four patients (55 %) were in the first CR or PR at the time of transplant. BEAM was used as a high-dose regimen in 36 patients (82 %) and all patients received peripheral blood grafts. The median follow-up for survivors was 46 (2-108) months from ASCT. Three patients died early from transplant-related reasons translating into a 2-year non-relapse mortality of 7 %. Relapse incidence at 4 years after ASCT was 39 %, with no events occurring beyond 2.5 years after ASCT. PFS and OS were 54 % and 59 % at four years, respectively. There was a trend for better OS in patients transplanted in the first CR or PR compared to more advanced disease status (70 % vs. 43 %, p=0.053). Of note, patients with a history of celiac disease had superior PFS (70 % vs. 35 %, p=0.02) and OS (70 % vs. 45 %, p=0.052) whilst age, gender, disease stage, B-symptoms at diagnosis or high-dose regimen were not associated with OS or PFS. Conclusions: This study shows for the first time in a larger patient sample that ASCT is feasible in selected patients with EATL and can yield durable disease control in a significant proportion of the patients. Patients transplanted in first CR or PR appear to do better than those transplanted later. ASCT should be considered in EATL patients responding to initial therapy.