Achieving a Molecular Remission before Allogeneic Stem Cell Transplantation in Adult Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia: Impact on Relapse and Long Term Outcome

Allogeneic stem cell transplantation (alloHSCT) in first complete remission (CR1) remains the consolidation therapy of choice in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). The prognostic value of measurable levels of minimal residual disease (MRD) at time of conditioning is a matter of debate. We analyzed the predictive relevance of MRD levels before transplantation on the clinical outcome of Ph+ ALL patients treated with chemotherapy and imatinib in 2 consecutive prospective clinical trials. MRD evaluation before transplantation was available for 65 of the 73 patients who underwent an alloHSCT in CR1. A complete or major molecular response at time of conditioning was achieved in 24 patients (37%), whereas 41 (63%) remained carriers of any other positive MRD level in the bone marrow. MRD negativity at time of conditioning was associated with a significant benefit in terms of risk of relapse at 5 years, with a relapse incidence of 8% compared with 39% for patients with MRD positivity (P\u2009=\u2009.007). However, thanks to the post-transplantation use of tyrosine kinase inhibitors (TKIs), disease-free survival was 58% versus 41% (P\u2009=\u2009.17) and overall survival was 58% versus 49% (P\u2009=\u2009.55) in MRD-negative compared with MRD-positive patients, respectively. The cumulative incidence of nonrelapse mortality was similar in the 2 groups. Achieving a complete molecular remission before transplantation reduces the risk of leukemia relapse even though TKIs may still rescue some patients relapsing after transplantation

Busulfan or Treosulfan Conditioning Platform for Allogeneic Stem Cell Transplantation in Patients Aged >60 y with Acute Myeloid Leukemia/Myelodysplastic Syndrome: A Subanalysis of the GITMO AlloEld Study

Background. The conditioning regimens with different alkylators at different doses can influence the outcome of allogeneic stem cell transplantation (SCT), but conclusive data are missing. Methods. With the aim to analyze real-life allogeneic SCTs performed in Italy between 2006 and 2017 in elderly patients (aged >60 y) with acute myeloid leukemia or myelodysplastic syndrome, we collected 780 first transplants data. For analysis purposes, patients were grouped according to the type of alkylator included in the conditioning (busulfan [BU]-based; n = 618; 79%; treosulfan [TREO]-based; n=162; 21%). Results. No significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival, although in the TREO-based group, we observed a greater proportion of elderly patients (P < 0.001); more active diseases at the time of SCT (P < 0.001); a higher prevalence of patients with either hematopoietic cell transplantation-comorbidity index ≥3 (P < 0.001) or a good Karnofsky performance status (P = 0.025); increased use of peripheral blood stem cells as graft sources (P < 0.001); and greater use of reduced intensity conditioning regimens (P = 0.013) and of haploidentical donors (P < 0.001). Moreover, the 2-y cumulative incidence of relapse with myeloablative doses of BU was significantly lower than that registered with reduced intensity conditioning (21% versus 31%; P = 0.0003). This was not observed in the TREO-based group. Conclusions. Despite a higher number of risk factors in the TREO group, no significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival according to the type of alkylator, suggesting that TREO has no advantage over BU in terms of efficacy and toxicity in acute myeloid leukemia and myelodysplastic syndrome

CO2 hydrogenation and ethanol steam reforming over Co/SiO2 catalysts: Deactivation and selectivity switches

Two 20 wt.% Co/SiO2 catalysts have been prepared using silica gel as a support and cobalt acetate or nitrate as precursors. They were characterized before and after reaction using XRD, skeletal IR and DR-UV\u2013vis-NIR spectroscopies and FE-SEM microscopy. Fresh catalysts are active in CO2 methanation at atmospheric pressure but rapidly deactivate at 623\u2013673 K, due to formation of encapsulating carbon. However, they retain a more stable activity in producing CO by the reverse water gas shift (rWGS) reaction. Methanation and rWGS appear to occur on independent sites. The Co/SiO2 catalyst produced from Co-acetate precursor shows stable activity in Ethanol Steam Reforming (ESR) at 873 12973 K, producing also carbon whiskers (nanotubes) that, however, do not cause catalyst deactivation at the laboratory conditions and timescale. The catalyst produced starting with Co-nitrate is even more active in ESR but it deactivates fast. At lower temperature or when deactivated with respect to ESR, both catalysts shift to high activity in ethanol dehydrogenation to acetaldehyde, showing that the ability to activate water is mostly lost. The differences observed among catalysts produced from cobalt acetate and cobalt nitrate precursors can be associated to the different pH of the impregnating solution. The higher pH of cobalt acetate solution results in surface dissolution / hydrolysis of silica and this may be at the origin of the formation of cobalt silicate surface species, which can also stabilize the support against high temperature reactivity. This might favor larger Co particles formation, less active, but also giving rise to inert cobalt species

Support effects in metal catalysis: a study of the behavior of unsupported and silica-supported cobalt catalysts in the hydrogenation of CO2 at atmospheric pressure

Two 20 wt.% Co/SiO2 catalysts were prepared using silica gel as a support and cobalt acetate and nitrate as precursors, respectively. As a comparison unsupported amorphous cobalt nanoparticles (10\u201380 nm) were synthesized by decomposing cobalt carbonyl. They were characterized before and after reaction using XRD, IR spectroscopy in the range of framework vibrations, DR-UV\u2013vis-NIR spectroscopies and FE-SEM microscopy. They are active in CO2 methanation at atmospheric pressure. However, unsupported cobalt and the silica-supported catalyst prepared using cobalt acetate deactivate fast at 623\u2013673 K, also due to formation of encapsulating carbon. On the other hand, they retain more stable activity in the reverse water gas shift (rWGS) reaction, producing CO. Methanation and rWGS appear to occur on independent sites. The silica-supported catalyst produced from cobalt nitrate show more stable methanation activity, attributed to the presence of smaller cobalt particles (10\u201320 nm) that resist deactivation. For both unsupported CoNPs and Co/SiO2, the significant parameters for catalysts deactivation have been determined for CO2 methanation. The differences observed among catalysts produced starting from cobalt acetate and cobalt nitrate, can be associated to the different pH of the impregnating solution

A study on CO2 methanation and steam methane reforming over commercial Ni/calcium aluminate catalysts

Three Ni-based natural gas steam reforming catalysts, i.e., commercial JM25-4Q and JM57-4Q, and a laboratory-made catalyst (26% Ni on a 5% SiO2-95% Al2O3), are tested in a laboratory reactor, under carbon dioxide methanation and methane steam reforming operating conditions. The laboratory catalyst is more active in both CO2 methanation (equilibrium is reached at 623 K with 100% selectivity) and methane steam reforming (92% hydrogen yield at 890 K) than the two commercial catalysts, likely due to its higher nickel loading. In any case, commercial steam reforming catalysts also show interesting activity in CO2 methanation, reduced by K-doping. The interpretation of the experimental results is supported by a one-dimensional (1D) pseudo-homogeneous packed-bed reactor model, embedding the Xu and Froment local kinetics, with appropriate kinetic parameters for each catalyst. In particular, the H2O adsorption coefficient adopted for the commercial catalysts is about two orders of magnitude higher than for the laboratory-made catalyst, and this is in line with the expectations, considering that the commercial catalysts have Ca and K added, which may promote water adsorption

Modeling of laboratory steam methane reforming and CO2 methanation reactors

To support the interpretation of the experimental results obtained from two laboratory-scale reactors, one working in the steam methane reforming (SMR) mode, and the other in the CO2 hydrogenation (MCO2) mode, a steady-state pseudo-homogeneous 1D non-isothermal packed-bed reactor model is developed, embedding the classical Xu and Froment local kinetics. The laboratory reactors are operated with three different catalysts, two commercial and one homemade. The simulation model makes it possible to identify and account for thermal effects occurring inside the catalytic zone of the reactor and along the exit line. The model is intended to guide the development of small size SMR and MCO2 reactors in the context of Power-to-X (P2X) studies

Ni/SiO2-Al2O3 catalysts for CO2 methanation: Effect of La2O3 addition

Ni-based catalysts, 13.5 Ni wt.%, with enhanced thermal stability and catalytic performance for CO2 methanation have been synthesized with different La2O3 loadings. Catalysts have been extensively characterised by: XRD, IR, H2-TPR, IPA-TPD, UV\u2013vis-NIR, FE-SEM and tested in CO2 methanation. SiO2 addition to Al2O3 support decreases the activity for CO2 methanation, while lanthanum acts as suitable promoter by strongly increasing catalytic performances. Silica presence successfully inhibits the formation of crystalline perovskites phases, stabilizes support morphology, and allows the introduction of high La2O3 loadings, allowing a better control of acid-base properties. 37 % wt. La2O3 addition gives rise to even higher performances than those previously observed, i.e. 83 % CH4 yield at 573 K. Reaction orders for CO2 and H2 have been determined; La- addition is confirmed to be responsible for a reduction in the CO2 reaction order, suggesting a stronger CO2 adsorption and the possible role of these species as a reactant reservoirs