Search

Les lymphomes T cutanés (CTCL) à un stade avancé sont des maladies rares, généralement réfractaires et mortelles. Des séries de cas ont suggéré que la greffe de cellules souches hématopoïétiques allogéniques (allogreffe) pourrait améliorer le pronostic des CTCL à un stade avancé. L’objectif de cette étude était d’étudier l’effet l’allogreffe sur l’évolution des personnes atteintes de CTCL au stade avancé.

Two different TiO2/SiO2compounds containing TiO2nanodomains dispersed over SiO2were investigated applying the AEIR method at the adsorption equilibrium of NH3and H2O from 300 to 723 K, particularly for the measurement of the individual heats of adsorption of the different species on Lewis acidic sites (LAS) and Brønsted acidic sites (BAS) as evaluation of the strength of the sites. It revealed two types of NH3adsorption sites: the first ones could correspond either to NH3species H-bonded to free OH groups or to coordinated weak LAS (named L1). The second ones (L2) were attributed to strongest LAS similar to those present at the surface of TiO2nanocrystallites. They also correspond to the stronger adsorption sites of H2O. Two types of Brønsted acid sites (BAS) were additionally evidenced by the AEIR method and proposed to be specifically located on the Si–O–Ti bridging bonds at the TiO2/SiO2interface. The heats of adsorption of the different adsorbed species provided by the AEIR method were consistent with literature data on average values of the heats of adsorption of NH3and H2O from microcalorimetry measurements. The surface acidity of the two compounds in the presence of H2O was determined using NH3–H2O coadsorption. At T≥ 473 K, the NH3species on the L2 sites were not significantly displaced from the surface whatever the partial pressure of H2O studied in agreement with the Temkin competitive model using the individual heats of adsorption of the NH3and H2O species. This model also revealed the presence of a small amount of H2O species adsorbed on L2 sites allowing H2O dissociation or/and hydrolysis of SiOTi or TiOTi bridges, leading to the formation of a much higher amount of BAS. Therefore, this original work combining the AEIR method and the Temkin competitive model provided new insights for understanding water effects on acidic oxide catalysts.

The electron paramagnetic resonance (EPR) technique was used to study the behavior of the asphaltenes from the Merey crude oil (ASCM), its vacuum residue (ARVM), its fractions, and trapped compounds (A1-ASCM, A2-ASCM, TC-ASCM, A1-ARVM, A2-ARVM, and TC-ARVM). Asphaltenes were precipitated from Merey heavy crude oil and its vacuum residue. The fractionation of our petroleum asphaltenes was carried out using the para-nitrophenol (PNP) method. Two fractions named A1and A2and trapped compounds were obtained. The temperature dependence of the EPR spectra was used to obtain a set of temperatures related to free radical (FR) generation and recombination. From the analysis of the EPR spectrum of the most intense signal of the vanadium, we obtain the temperature ranges of the anisotropic-to-isotropic domains, we found a nonlinear behavior of the B parameter in the temperature range studied, and we propose a functional relationship for this parameter as a function of the temperature. On the other hand, we found the temperatures for the slow-to-fast motion regime in these samples and correlated it with the mobility of the fractions.

In 2013, the interim analysis of the Protocol for Herceptin as Adjuvant therapy with Reduced Exposure (PHARE) trial could not show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. Here, we report the planned final analysis based on the prespecified number of occurring events.

The electron paramagnetic resonance (EPR) technique is used to evaluate the temperature dependence of the aggregation processes in asphaltenes of heavy and extra-heavy crude oils and their vacuum residues from the Venezuelan Oil Belt. All of the EPR spectra of the samples studied show an intense central signal assigned to free radicals (FRs) and a multiplet as a result of the presence of a V+4porphyrin. From the analyses of the inverse of the normalized area as a function of the temperature for the FR signal and the most intense peak in the vanadium multiplet, we obtain a set of temperatures related to the transition of fast-to-slow motion regions, the temperature of generation–recombination of FRs, and the cracking temperature in all of the samples. On the other hand, applying a Curie–Weiss law, we obtain the order–disorder temperatures and correlated them with the American Petroleum Institute grade of the samples. A computational simulation was performed to propose possible conformers based on the experimental data to confirm our results, which can be used as a probe of the structural and conformational changes in the asphaltene structure.

Ethanol and methanol are converted using H-ZSM-5 zeolite at 623 K and 3.0 MPa into identical hydrocarbons (paraffins, olefins and aromatics) and moreover with identical selectivities. The distribution of olefins as paraffins follows the Flory distribution with a growth probability of 0.53. Regardless of the alcohol, the catalyst lifetime and selectivity into hydrocarbons C3+are high in spite of an important coke content. The coke that poisons the Brønsted acid sites without blocking their access is composed in part of radical polyalkylaromatics. The addition of hydroquinone, an inhibitor of radicals, to the feed, provokes an immediate catalyst deactivation.

Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial. After RIC-UCBT, NK cells displayed phenotypic features of both activation and immaturity. Restoration of their polyfunctional capacities depended on the timing of their acquisition of phenotypic markers of maturity. The incidence of treatment-related mortality (TRM) was correlated with low CD16 expression (P=0.043) and high HLA-DR expression (P=0.0008), whereas overall survival was associated with increased frequency of NK-cell degranulation (P=0.001). These features reflect a general impairment of the NK licensing process in HLA-mismatched HSCT and may aid the development of future strategies for selecting optimal UCB units and enhancing immune recovery.

Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed Hodgkin lymphoma (HL). When an HLA-matched donor is lacking a graft from a familial haploidentical (HAPLO) donor, a mismatched unrelated donor (MMUD) or cord blood (CB) might be considered. In this retrospective study, we compared the outcome of patients with HL undergoing a RIC or NMA allo-SCT from HAPLO, MMUD or CB. Ninety-eight patients were included. Median follow-up was 31 months for the whole cohort. All patients in the HAPLO group (N=34) received a T-cell replete allo-SCT after a NMA (FLU-CY-TBI, N=31, 91%) or a RIC (N=3, 9%) followed by post-transplant cyclophosphamide. After adjustment for significant covariates, MMUD and CB were associated with significantly lower GvHD-free relapse-free survival (GRFS; hazard ratio (HR)=2.02, P=0.03 and HR=2.43, P=0.009, respectively) compared with HAPLO donors. In conclusion, higher GRFS was observed in Hodgkin lymphoma patients receiving a RIC or NMA allo-SCT with post-transplant cyclophosphamide from HAPLO donors. Our findings suggest they should be favoured over MMUD and CB in this setting.

Peripheral T-cell lymphoma carries a poor prognosis. To document a possible graft-versus-lymphoma effect in this setting, we evaluated the impact of immunomodulation in 63 patients with peripheral T-cell lymphoma who relapsed after allogeneic transplant in 27 SFGM-TC centers. Relapse occurred after a median of 2.8 months. Patients were then treated with non-immunologic strategies (chemotherapy, radiotherapy) and/or immune modulation (donor lymphocyte infusions (DLI) and/or discontinuation of immunosuppressive therapy). Median overall survival (OS) after relapse was 6.1 months (DLI group: 23.6 months, non-DLI group: 3.6 months). Among the 14 patients who received DLI, 9 responded and 2 had stable disease. Among the remaining 49 patients, a complete response accompanied by extensive chronic GvHD was achieved in two patients after tapering of immunosuppressive drugs. Thirty patients received radio-chemotherapy, with an overall response rate of 50%. In multivariate analysis, chronic GvHD (odds ratio: 11.25 (2.68–48.21), P=0.0009) and skin relapse (odds ratio: 4.15 (1.04–16.50), P=0.043) were associated with a better response to treatment at relapse. In a time-dependent analysis, the only factor predictive of OS was the time from transplantation to relapse (hazards ratio: 0.33 (0.17–0.640), P=0.0009). This large series provides encouraging evidence of a true GvL effect in this disease.

Ethanol and methanol are converted using H-ZSM-5 zeolite at 623 K and 3.0 MPa into identical hydrocarbons (paraffins, olefins and aromatics) and moreover with identical selectivities. The distribution of olefins as paraffins follows the Flory distribution with a growth probability of 0.53. Regardless of the alcohol, the catalyst lifetime and selectivity into hydrocarbons C3+are high in spite of an important coke content. The coke that poisons the Brønsted acid sites without blocking their access is composed in part of radical polyalkylaromatics. The addition of hydroquinone, an inhibitor of radicals, to the feed, provokes an immediate catalyst deactivation.

Malgré les travaux théoriques mettant en relation les troubles des conduites (TC) avec les difficultés de régulation émotionnelle, peu de recherches expérimentales ont exploré les liens entre ces deux variables. Cette étude visait à étudier les liens entre TC et régulation émotionnelle chez 75 adolescents : 30 adolescents avec TC et 45 témoins, âgés de 13 à 18ans. La régulation émotionnelle a été mesurée à l’aide de deux auto-questionnaires : la TAS-20 (questionnaire d’alexithymie de Toronto), considérée comme le gold standardpour mesurer l’alexithymie, et la DERS (Difficulties in Emotion Regulation Scale), une échelle de régulation émotionnelle récemment validée. Les résultats ont mis en évidence que les témoins et les adolescents avec TC présentaient des scores de régulation émotionnelle significativement différents. De plus, les corrélations ont montré que, plus les difficultés de régulation émotionnelle étaient importantes, plus les TC étaient sévères. Enfin, d’après les analyses discriminantes, les deux outils utilisés pour décrire les modalités de régulation émotionnelle se sont révélés efficaces pour prédire l’appartenance d’un participant au groupe TC ou au groupe témoin de manière significative. Les résultats vont dans le sens des travaux ayant souligné le lien théorique entre un défaut de mentalisation (i.e. accès et compréhension des états internes) et le passage à l’acte. Ils encouragent le développement de programmes thérapeutiques centrés sur la régulation émotionnelle à l’attention d’adolescents avec TC.

L’allogreffe de cellules souches hématopoïétiques (CSH) se complique de pneumopathies qui peuvent lourdement grever la mortalité liée à la procédure.

The authors have previously shown that mononuclear cells derived from patients with resistant chronic graft-versus-host-disease (GVHD) express high calcineurin (CN) activity, suggesting that in vitro assessment of CN activity may be a useful index to estimate the degree of immunosuppression afforded by cyclosporine A (CsA). The goal of this study was to assess CN activity during the first 2 months after allogeneic stem-cell transplantation (SCT) and to correlate its evolution with the occurrence of acute GVHD.

The effect of the lipase from Burkholderia cepacia(previously known as Pseudomonas cepacia) on the gelation kinetics and gel structure was examined on a type of silica aerogel made from a mixture of methyltrimethoxysilane and tetramethoxysilane. For this purpose, gels were made with increasing concentrations of lipase in otherwise constant other conditions (pH, water and Si precursors concentrations). It was found that the enzyme accelerated the gelation kinetics, hence was participating in some way to the hydrolysis of the silica precursor. The structure of the gel was simultaneously modified to produce an increasing proportion of Q4silicon sites.

The effect of the porous texture of silica gels on the catalytic efficiency of enzymes was investigated by submitting similarly prepared aerogels to different postgelation treatments in liquid media. The samples investigated comprised wet gels aged either in water at different pH, in an organic solvent miscible with water (dioxane) containing different water concentrations, or in an organic solvent immiscible with water (isooctane). Aerogels were obtained after aging by supercritically drying the samples with carbon dioxide. Some gels were also partially dried by evaporation for increasing periods of time prior to a final drying step with supercritical CO2. The evolution of the pore texture of these materials was analyzed from their nitrogen adsorption isotherms. The esterification activities of the lipase Pseudomonas cepacia immobilized in the various gels were compared. Results show that the evolution in the texture of the silica aerogel resulted in a change in the lipase activity. This suggests that the enzyme can be considered as a gel type material, whose behavior to transformations in liquid media is similar, to some extent, to that of silica aerogels.

The biosynthesis of lignin monomers involves two methylation steps catalyzed by orthodiphenol-O-methyltransferases: caffeic acid/5-hydroxyferulic acid 3/5-O-methyltransferases (COMTs) and caffeoyl-coenzyme A (CoA)/5-hydroxyferuloyl-CoA 3/5-O-methyltransferases (CCoAOMTs). Two COMT classes (I and II) were already known to occur in tobacco (Nicotiana tabacum) and three distinct CCoAOMT classes have now been characterized. These three CCoAOMT classes displayed a maximum level of expression at different stages of stem development, in accordance with their involvement in the synthesis of lignin guaiacyl units. Expression profiles upon tobacco mosaic virus infection of tobacco leaves revealed a biphasic pattern of induction for COMT I, COMT II, and CCoAOMTs. The different isoforms were expressed in Escherichia coli and our results showed that CCoAOMTs and, more surprisingly, COMTs efficiently methylated hydroxycinnamoyl-CoA esters. COMT I was also active toward 5-hydroxyconiferyl alcohol, indicating that COMT I that catalyzes syringyl unit synthesis in planta may operate at the free acid, CoA ester, or alcohol levels. COMT II that is highly inducible by infection also accepted caffeoyl-CoA as a substrate, thus suggesting a role in ferulate derivative deposition in the walls of infected cells. Tobacco appears to possess an array of O-methyltransferase isoforms with variable efficiency toward the diverse plant o-diphenolic substrates.

In view of a possible future programme of physics with low-energy antiprotons, a simplified scheme for the provision of antiprotons at 100 MeV/c has been studied. It uses the present target area and the modified Antiproton Collector (AC) in its present location. In this report the modifications and the operation are discussed.

Abstract: In view of a future antihydrogen programme at CERN, the options for producing MeV antiprotons are revisited. The current limitations, operational performances and foreseen improvements are detailed. An alternative scheme using a dedicated machine for production and deceleration is also discussed.

Dividing eukaryotic cells expressing the herpes simplex virus type 1 thymidine kinase (TK) gene are sensitive to the cytotoxic effect of nucleoside analogs such as acyclovir or ganciclovir (GCV). Transgenic mice with cell-targeted expression of this conditional toxin have been used to create animals with temporally controlled cell-specific ablation. In these animal models, which allow the study of the physiological importance of a cell type, males are sterile. In this study, we showed that this phenomenon is due to testis-specific high-level expression of short TK transcripts initiated mainly upstream of the second internal ATG of the TK gene. This expression is DNA methylation independent. To obtain a suicide gene that does not cause male infertility, we generated and analyzed the properties of a truncated TK (delta TK) lacking the sequences upstream of the second ATG. We showed that when expressed at sufficient levels, the functional properties of delta TK are similar to those of TK in terms of thymidine or GCV phosphorylation. This translated into a similar GCV-dependent toxicity for delta TK- or TK-expressing cells, both in vitro and in transgenic mice. However, delta TK behaved differently from TK in two ways. First, it did not cause sterility in delta TK transgenic males. Second, low-level delta TK RNA expression did not confer sensitivity to GCV. The uses of delta TK in cell-specific ablation in transgenic mice and in gene therapy are discussed.

OBJECTIVE: To determine whether multiple dosing of acetaminophen would result in drug accumulation in polymedicated elderly patients with rheumatic pain. METHODS: Twelve inpatients (11 women), aged 89 +/- 4 years, weight 59 +/- 10 kg, receiving 3 to 8 concomitant medications, entered the study. Their creatinine clearance according to the Cockroft-Gault formula was 42 +/- 12 ml/min. The pharmacokinetics of 1 g acetaminophen was evaluated after the first dose (D1) and after the last dose (D7) during a 3 times daily regimen of 1 g for 5 consecutive days. RESULTS: The plasma pharmacokinetic profile of acetaminophen did not change significantly at D7 compared to D1. No significant within-patient differences were observed, especially with respect to plasma elimination half-life (2.74 +/- 0.48 and 2.77 +/- 0.32 hours, respectively), area under the concentration-time curve (82.5 +/- 21.1 and 90.1 +/- 15.2 microg x h/ml, respectively), and apparent oral clearance (3.68 +/- 0.85 and 3.28 +/- 0.52 ml/min/kg, respectively). CONCLUSION: No drug accumulation occurred during multiple dosing with acetaminophen in these very old subjects. On the basis of pharmacokinetic data alone, a dose regimen of acetaminophen 1 g tid seems to be appropriate in such patients.

Following the pioneering work on lithium lenses at INP, Novosibirsk, a 2 cm diameter lens was designed and built at Fermilab as an antiproton collector for the antiproton source of the Tevatron I project. A lens of this type was tested at the CERN Antiproton Accumulator (AA) as an antiproton collector and then as a prefocusing element before the AA pulsed current target. In the latter case the purpose was to increase the proton beam convergence at the target to compensate the defocusing effect on the proton beam of the current in the target. As an antiproton collector the lithium lens performed as predicted increasing the antiproton yield into the AA by 40%. In the prefocusing configuration beam convergence and spot size on the target were considerably improved over the standard arrangement using a pulsed quadrupole triplet and the lens has survived 1.4 M pulses of current from 290 to 350 kA in a 26 GeV/c beam of up to 1.4 × 1013 protons.

The process development by IFP Energies nouvelles (IFPEN)/ENI/Axens of a Fischer-Tropsch process is described. This development is based on upstream process studies to choose the process scheme, reactor technology and operating conditions, and downstream to summarize all development work in a process guide. A large amount of work was devoted to the catalyst performances on one hand and the scale-up of the slurry bubble reactor with dedicated complementary tools on the other hand. Finally, an original approach was implemented to validate both the process and catalyst on an industrial scale by combining a 20 bpd unit in ENI’s Sannazzaro refinery, with cold mock-ups equivalent to 20 and 1 000 bpd at IFPEN and a special “Large Validation Tool” (LVT) which reproduces the combined effect of chemical reaction condition stress and mechanical stress equivalent to a 15 000 bpd industrial unit. Dedicated analytical techniques and a dedicated model were developed to simulate the whole process (reactor and separation train), integrating a high level of complexity and phenomena coupling to scale-up the process in a robust reliable base on an industrial scale.

The aim of this retrospective multicentric study was to assess the results of 112 consecutive umbilical cord blood transplantations (UCBT) following nonmyeloablative conditioning (NMA) performed in 20 French centres, between October 2003 and March 2007.Characteristics of the patients : Underlying disease: acute leukaemia: myeloid 60, lymphoblastic 17, lymphoma: 15, myelodysplasia: 5, myeloma: 4, Hodgkin: 4, chronic leukaemia: myeloid 3 and lymphoid 3 and 1 solid tumor. Median age at transplantation: 44 y (16–69), median weight: 62 kg (42–125), male: 49 (43%), CMV seropositivity: 64% ; 32 pts had received previous autologous and 3 allogeneic transplantation. The time between diagnosis and transplant was 19 months (3–174). Disease status at transplantation was early (31%), intermediate (37%) and advanced (32%). Median follow-up was 7 months (2–38). The original Minneapolis conditioning regimen was used in 106 (96%) pts and modified in 6 (4 or 6 Gy TBI: 4 pts; ATG: 2). Characteristics of the grafts: A single unit was infused in 77 pts (69%), two in 35 (31%). HLA compatibility was 6/6 in 6 pts, 5/6 in 36, 4/6 in 60, ≤ 3/6 in 6 ; 43 pts were ABO matched. Infused nucleated cells (NC) was 3.1×107/kg (1–9): 2.9 × 107/kg in single units and 3.7 × 107/kg in double units. Results: Neutrophils recovery was 85±4% at a median of 19 days (0–48) ; 14% pts experienced autologous recovery; 14% had mixed and 72% full donor chimerism at D+100. Univariate analysis indicated the low weight, previous transplantation, double units and HLA compatibility as significant factors for neutrophil recovery; however multivariate analysis did not find any significant factor. Acute GVHD was observed in 34±5% of pts: 21, 12 and 5 pts had grade II, III or IV aGVHD respectively and chronic GVHD in 16%. Non relapse mortality was 12±3% at 6 months ; relapse: 22±5% ; overall survival: 72±5%. Causes of death were relapse in 17 pts, GVHD in 2 pts, venocclusive disease and multiorgan failure in 5, infections in 4 and other toxicity in 3. DFS at 6 and 24 months were 68±5% and 65±5%, respectively. By univariate analysis, risk factors for DFS were age (>44y), weight, previous transplant, HLA disparity (0+1 vs 2+3), and NC dose (<3.1× 107/kg). Multivariate analysis identified 3 independent risk factors: HLA disparity, cell dose and age were still significant. This French experience of UCBT after NMA confirms the good results of the Minneapolis group (Brunstein et al. Blood 2007). Few events were observed between 6 and 24 mo and DFS remains high, however a longer follow up is needed. A prospective study of UCBT after NMA conditioning in AML is ongoing in France to identify the risk factors for DFS in a more homogeneous group of pts.

The aim of this retrospective multicentric study was to assess the results of 112 consecutive umbilical cord blood transplantations (UCBT) following nonmyeloablative conditioning (NMA) performed in 20 French centres, between October 2003 and March 2007.Characteristics of the patients : Underlying disease: acute leukaemia: myeloid 60, lymphoblastic 17, lymphoma: 15, myelodysplasia: 5, myeloma: 4, Hodgkin: 4, chronic leukaemia: myeloid 3 and lymphoid 3 and 1 solid tumor. Median age at transplantation: 44 y (16–69), median weight: 62 kg (42–125), male: 49 (43%), CMV seropositivity: 64% ; 32 pts had received previous autologous and 3 allogeneic transplantation. The time between diagnosis and transplant was 19 months (3–174). Disease status at transplantation was early (31%), intermediate (37%) and advanced (32%). Median follow-up was 7 months (2–38). The original Minneapolis conditioning regimen was used in 106 (96%) pts and modified in 6 (4 or 6 Gy TBI: 4 pts; ATG: 2). Characteristics of the grafts: A single unit was infused in 77 pts (69%), two in 35 (31%). HLA compatibility was 6/6 in 6 pts, 5/6 in 36, 4/6 in 60, ≤ 3/6 in 6 ; 43 pts were ABO matched. Infused nucleated cells (NC) was 3.1×107/kg (1–9): 2.9 × 107/kg in single units and 3.7 × 107/kg in double units. Results: Neutrophils recovery was 85±4% at a median of 19 days (0–48) ; 14% pts experienced autologous recovery; 14% had mixed and 72% full donor chimerism at D+100. Univariate analysis indicated the low weight, previous transplantation, double units and HLA compatibility as significant factors for neutrophil recovery; however multivariate analysis did not find any significant factor. Acute GVHD was observed in 34±5% of pts: 21, 12 and 5 pts had grade II, III or IV aGVHD respectively and chronic GVHD in 16%. Non relapse mortality was 12±3% at 6 months ; relapse: 22±5% ; overall survival: 72±5%. Causes of death were relapse in 17 pts, GVHD in 2 pts, venocclusive disease and multiorgan failure in 5, infections in 4 and other toxicity in 3. DFS at 6 and 24 months were 68±5% and 65±5%, respectively. By univariate analysis, risk factors for DFS were age (>44y), weight, previous transplant, HLA disparity (0+1 vs 2+3), and NC dose (<3.1× 107/kg). Multivariate analysis identified 3 independent risk factors: HLA disparity, cell dose and age were still significant. This French experience of UCBT after NMA confirms the good results of the Minneapolis group (Brunstein et al. Blood 2007). Few events were observed between 6 and 24 mo and DFS remains high, however a longer follow up is needed. A prospective study of UCBT after NMA conditioning in AML is ongoing in France to identify the risk factors for DFS in a more homogeneous group of pts.

Survival after HSCT from HLA-identical siblings is inferior in SAA patients 30 years or older as compared with younger patients, with long-term overall survival of 58% and 80%, respectively (Bacigalupo et al, Semin in Hematol 2000). In order to improve survival in patients >30 years, the use of a less toxic regimen including low dose cyclophosphamide (<200 mg/kg) in combination with ATG, while adding fludarabine, might be an option to explore with the aim to reduce transplant-related mortality (Marsh et al, Br J Haematol, 2003). In order to evaluate the toxicity profile, engraftment potential, and efficacy of HLA-identical HSCT using such fludarabine-based conditioning regimen, we conducted this study from the SFGM-TC and GITMO databases, focussing on patients older than 30 years or those younger than 30 years but with co-morbidities at HSCT. From December 1998 to June 2004, 15 HSCT were performed in 14 patients (median age 39 years, range 16–60 years), for idiopathic SAA (n=13), or paroxysmal nocturnal hemoglobinuria (PNH) (n=1). HSCT was performed either as first-line treatment (n=8), or after failure of immune suppression with ATG/ciclosporine (CsA) (n=4), or failure of a first allogeneic HSCT (n=3). In addition to fludarabine (120 mg/m2) and ATG (3.75 mg/kg x 2 to 4 days), the patients received two different reduced doses of cyclophosphamide of 120 mg/kg (n=4) or 20 mg/kg (n=9). Two patients received only ATG and fludarabine (175 mg/m2) without cyclophosphamide. Marrow (n=12, median dose of nucleated cells 5.108/kg, range 2–15.108/kg) or PBSC (n=3) grafts were unmanipulated. GVHD prophylaxis consisted of CsA/methotrexate (n=11), CsA alone (n=1), methotrexate alone (n=1), or nothing (n=2 second grafts). Graft rejection occurred in one patient, who received a second graft from the same donor with the same conditioning regimen (fluda/ATG/cyclophosphamide 20 mg/kg) successfully. All other patients engrafted with a neutrophil (ANC >500 cells/μL) and platelet (PLT >50 000/μL) recovery occurring at a median of 18 days (range 12–28 days), and 26 days (range 11–272 days) after transplant, respectively. Acute GVHD occurred in 3 patients with a maximum grade II in 2 patients and grade III in one. Among 11 evaluable patients, six developed chronic GVHD (limited in 3 cases). Four patients died of infection (n=3) or multi-organ failure (n=1), within the 3 months post-HSCT for 3 of them. With a median follow-up of 28 months (range 11–48 months), 10/14 patients survived with long-term engraftment and full (n=8) or mixed (n=2) donor chimerism (KM probability of long-term survival 71%-see figure). In conclusion, reduced intensity fludarabine-based conditioning regimen is feasible in SAA patients over the age of 30 and produces encouraging survival: a prospective trial is being conducted within the European Group for Blood and Marrow Transplantation (EBMT). Figure Figure

Survival after HSCT from HLA-identical siblings is inferior in SAA patients 30 years or older as compared with younger patients, with long-term overall survival of 58% and 80%, respectively (Bacigalupo et al, Semin in Hematol 2000). In order to improve survival in patients >30 years, the use of a less toxic regimen including low dose cyclophosphamide (<200 mg/kg) in combination with ATG, while adding fludarabine, might be an option to explore with the aim to reduce transplant-related mortality (Marsh et al, Br J Haematol, 2003). In order to evaluate the toxicity profile, engraftment potential, and efficacy of HLA-identical HSCT using such fludarabine-based conditioning regimen, we conducted this study from the SFGM-TC and GITMO databases, focussing on patients older than 30 years or those younger than 30 years but with co-morbidities at HSCT. From December 1998 to June 2004, 15 HSCT were performed in 14 patients (median age 39 years, range 16–60 years), for idiopathic SAA (n=13), or paroxysmal nocturnal hemoglobinuria (PNH) (n=1). HSCT was performed either as first-line treatment (n=8), or after failure of immune suppression with ATG/ciclosporine (CsA) (n=4), or failure of a first allogeneic HSCT (n=3). In addition to fludarabine (120 mg/m2) and ATG (3.75 mg/kg x 2 to 4 days), the patients received two different reduced doses of cyclophosphamide of 120 mg/kg (n=4) or 20 mg/kg (n=9). Two patients received only ATG and fludarabine (175 mg/m2) without cyclophosphamide. Marrow (n=12, median dose of nucleated cells 5.108/kg, range 2–15.108/kg) or PBSC (n=3) grafts were unmanipulated. GVHD prophylaxis consisted of CsA/methotrexate (n=11), CsA alone (n=1), methotrexate alone (n=1), or nothing (n=2 second grafts). Graft rejection occurred in one patient, who received a second graft from the same donor with the same conditioning regimen (fluda/ATG/cyclophosphamide 20 mg/kg) successfully. All other patients engrafted with a neutrophil (ANC >500 cells/μL) and platelet (PLT >50 000/μL) recovery occurring at a median of 18 days (range 12–28 days), and 26 days (range 11–272 days) after transplant, respectively. Acute GVHD occurred in 3 patients with a maximum grade II in 2 patients and grade III in one. Among 11 evaluable patients, six developed chronic GVHD (limited in 3 cases). Four patients died of infection (n=3) or multi-organ failure (n=1), within the 3 months post-HSCT for 3 of them. With a median follow-up of 28 months (range 11–48 months), 10/14 patients survived with long-term engraftment and full (n=8) or mixed (n=2) donor chimerism (KM probability of long-term survival 71%-see figure). In conclusion, reduced intensity fludarabine-based conditioning regimen is feasible in SAA patients over the age of 30 and produces encouraging survival: a prospective trial is being conducted within the European Group for Blood and Marrow Transplantation (EBMT).

Discusses ways for associations to use fax-on-demand service. Generating income; Estimating volume; Building the list of documents; Promoting the service.