Conditioning Intensity, Pre-Transplant Flow Cytometric Measurable Residual Disease, and Outcome in Adults with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

How conditioning intensity is related to outcomes of AML patients undergoing allografting in morphologic remission is an area of great ongoing interest. We studied 743 patients in morphologic remission and known pre-transplant measurable residual disease (MRD) status determined by multiparameter flow cytometry (MFC) who received a first allograft after myeloablative, reduced intensity, or nonmyeloablative conditioning (MAC, RIC, and NMA). Overall, relapse-free survival (RFS) and overall survival (OS) were longer after MAC than RIC or NMA conditioning, whereas relapse risks were not different. Among MRD(pos)patients, 3-year estimates of relapse risks and survival were similar across conditioning intensities. In contrast, among MRD(neg)patients, 3-year RFS and OS were longer for MAC (69% and 71%) than RIC (47% and 55%) and NMA conditioning (47% and 52%). Three-year relapse risks were lowest after MAC (18%) and highest after NMA conditioning (30%). Our data indicate an interaction between conditioning intensity, MFC-based pre-transplant MRD status, and outcome, with benefit of intensive conditioning primarily for patients transplanted in MRD(neg)remission. Differing from recent findings from other studies that indicated MAC is primarily beneficial for some or all patients with MRD(pos)pre-HCT status, our data suggest MAC should still be considered for MRD(neg)AML patients if tolerated

Gas exchange of four woody species under salinity and soil waterlogging

ABSTRACT The objective of this study was to evaluate gas exchanges in seedlings of forest species grown in saline soils and subjected to soil waterlogging cycles. The experimental design was completely randomized in a factorial arrangement, with four forest species: Myracrodruon urundeuva Fr Allemão, Mimosa caesalpiniifolia Benth, Tabebuia impetiginosa (Mart. ex. DC.) Standl and Azadirachta indica A. Juss, two soil salinity levels (1.2 and 8.6 dS m-1) and two water regimes (with and without waterlogging). Measurements of stomatal conductance, transpiration and CO2 assimilation rate were performed before and after each waterlogging period. The interaction of the highest saline level (8.6 dS m-1) and waterlogging caused greater reductions in leaf gas exchange, except for Mimosa caesalpiniifolia Benth. Tabebuia impetiginosa (Mart. ex. DC.) Standl was the species with highest sensitivity to both studied factors of stress

Gas exchange of four woody species under salinity and soil waterlogging

<div><p>ABSTRACT The objective of this study was to evaluate gas exchanges in seedlings of forest species grown in saline soils and subjected to soil waterlogging cycles. The experimental design was completely randomized in a factorial arrangement, with four forest species: Myracrodruon urundeuva Fr Allemão, Mimosa caesalpiniifolia Benth, Tabebuia impetiginosa (Mart. ex. DC.) Standl and Azadirachta indica A. Juss, two soil salinity levels (1.2 and 8.6 dS m-1) and two water regimes (with and without waterlogging). Measurements of stomatal conductance, transpiration and CO2 assimilation rate were performed before and after each waterlogging period. The interaction of the highest saline level (8.6 dS m-1) and waterlogging caused greater reductions in leaf gas exchange, except for Mimosa caesalpiniifolia Benth. Tabebuia impetiginosa (Mart. ex. DC.) Standl was the species with highest sensitivity to both studied factors of stress.</p></div

Impact of pretransplant measurable residual disease on the outcome of allogeneic hematopoietic cell transplantation in adult monosomal karyotype AML

Allogeneic hematopoietic cell transplantation (HCT) is often unsuccessful for monosomal karyotype (MK) acute myeloid leukemia (AML). To what degree failures are associated with pretransplant measurable residual disease (MRD)—a dominant adverse-risk factor—is unknown. We therefore studied 606 adults with intermediate- or adverse-risk AML in morphologic remission who underwent allogeneic HCT between 4/2006 and 1/2019. Sixty-eight (11%) patients had MK AML, the majority of whom with complex cytogenetics. Before HCT, MK AML patients more often tested MRDpos by multiparameter flow cytometry (49 vs. 18%; P < 0.001) and more likely had persistent cytogenetic abnormalities (44 vs. 13%; P < 0.001) than non-MK AML patients. Three-year relapse/overall survival estimates were 46%/43% and 72%/15% for MRDneg and MRDpos MK AML patients, respectively, contrasted to 20%/64% and 64%/38% for MRDneg and MRDpos non-MK AML patients, respectively. After multivariable adjustment, MRDpos remission status but not MK remained statistically significantly associated with shorter survival and higher relapse risk. Similar results were obtained in several patient subsets. In summary, while our study confirms higher relapse rates and shorter survival for MK-AML compared with non-MK AML patients, these outcomes are largely accounted for by the presence of other adverse prognostic factors, in particular higher likelihood of pre-HCT MRD

Factors associated with outcomes after a second CD19-targeted CAR T-cell infusion for refractory B-cell malignancies

CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy has shown significant efficacy for relapsed or refractory (R/R) B-cell malignancies. Yet, CD19 CAR T cells fail to induce durable responses in most patients. Second infusions of CD19 CAR T cells (CART2) have been considered as a possible approach to improve outcomes. We analyzed data from 44 patients with R/R B-cell malignancies (acute lymphoblastic leukemia [ALL], n = 14; chronic lymphocytic leukemia [CLL], n = 9; non-Hodgkin lymphoma [NHL], n = 21) who received CART2 on a phase 1/2 trial (NCT01865617) at our institution. Despite a CART2 dose increase in 82% of patients, we observed a low incidence of severe toxicity after CART2 (grade >/=3 cytokine release syndrome, 9%; grade >/=3 neurotoxicity, 11%). After CART2, complete response (CR) was achieved in 22% of CLL, 19% of NHL, and 21% of ALL patients. The median durations of response after CART2 in CLL, NHL, and ALL patients were 33, 6, and 4 months, respectively. Addition of fludarabine to cyclophosphamide-based lymphodepletion before the first CAR T-cell infusion (CART1) and an increase in the CART2 dose compared with CART1 were independently associated with higher overall response rates and longer progression-free survival after CART2. We observed durable CAR T-cell persistence after CART2 in patients who received cyclophosphamide and fludarabine (Cy-Flu) lymphodepletion before CART1 and a higher CART2 compared with CART1 cell dose. The identification of 2 modifiable pretreatment factors independently associated with better outcomes after CART2 suggests strategies to improve in vivo CAR T-cell kinetics and responses after repeat CAR T-cell infusions, and has implications for the design of trials of novel CAR T-cell products after failure of prior CAR T-cell immunotherapies

Ecological aspects of Rhodnius nasutus Stål, 1859 (Hemiptera: Reduviidae: Triatominae) in palms of the Chapada do Araripe in Ceará, Brazil

The aim of this work is to present aspects related to the ecology of Rhodnius nasutus Stål, 1859 in palms from Chapada do Araripe in Ceará, Brazil. The following five species of palms were investigated: babaçu (Attalea speciosa), buriti (Mauritia flexuosa), carnaúba (Copernicia prunifera), catolé (Syagrus oleracea) and macaúba-barriguda (Acrocomia intumescens). Fifth palms were dissected (10 specimens for each species). The overall infestation index was 86%, with a total of 521 triatomines collected. The Trypanosoma cruzi Chagas, 1909 Index was 16.8% and two insects presented mixed infection with Trypanosoma rangeli Tejera, 1920. A precipitin test showed that R. nasutus from palms of Chapada do Araripe are associated with opossum and bird although other possible bloodmeals were observed. Our results showing a high index of infestation of the palms as well as T. cruzi infection, the association of R. nasutus with the most diverse species of palms and proximity of these palms to houses demonstrate the importance of this area for sylvatic T. cruzi transmission and suggest the need for epidemiological surveillance in the region of the Chapada do Araripe

Chronic total occlusion percutaneous coronary intervention in Latin America

Objectives To report clinical, angiographic characteristics, outcomes, and predictors of unsuccessful procedures in patients who underwent chronic total occlusion (CTO) percutaneous coronary interventions (PCI) in Latin America. Background CTO PCI has been increasingly performed worldwide, but there is a lack of information in this region. Methods An international multicenter registry was developed to collect data on CTO PCI performed in centers in Latin America. Patient, angiographic, procedural and outcome data were evaluated. Predictors of unsuccessful procedures were assessed by multivariable analysis. Results We have included data related to 1,040 CTO PCIs performed in seven countries in Latin America (Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, and Puerto Rico). The mean age was 64 +/- 10 years, and CTO PCI was performed mainly for angina control (81%) or treatment of a large ischemic area (30%). Overall technical success rate was 82.5%, and it was achieved with antegrade wire escalation in 81%, antegrade dissection/re-entry in 8% and with retrograde techniques in 11% of the successful procedures. Multivariable analysis identified moderate/severe calcification, a blunt proximal cap and a previous attempt as independent predictors of unsuccessful procedures. In-hospital major adverse cardiovascular events (MACE) occurred in 3.1% of the cases, death in 1% and cardiac tamponade in 0.9% Conclusions CTO PCI in Latin America has been performed mainly for ischemia relief. Procedures were associated with a success rate above 80% and low incidence of MACE. Predictors of unsuccessful procedures were similar to those previously reported in the literature.Brazilian Society of Interventional Cardiolog