Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

Effects of Different Nitrogen Dose and Sources as Top-Dressing on Yield and Silage Quality Attributes of Silage Maize

Effects of different nitrogen doses and sources applied as top-dressing on dry matter yield and quality of maize silage were investigated in this study. Along with 7.5 kg N da(-1) application as starter at sowing in the form of 15-15-0+Zn, nitrogen doses of 0, 7.5,15 and 22.5 kg da(-1) were applied as top-dressing at 6-leaf stage of plants in the forms of ammonium nitrate, urea, DMPP blended ammonium sulphate nitrate and urea with NBPT urease inhibitor. Experiments were conducted in randomized blocks-factorial experimental design with 3 replicates in 2013 and 2014. The greatest dry matter yield were obtained from 15 and 22.5 kg N da(-1) in 2013 and from 22.5 kg N da(-1) in 2014. Nitrogen sources had also significant effects on dry matter yield. According to the average of two years, both DMPP blended ammonium sulphate nitrate and urea with NBPT urease inhibitor increased yield respectively by 7 and 3% as compared to ammonium nitrate and urea fertilizers. Nitrogen doses significantly improved the silage quality attributes. Nitrogen treatments increased silage protein ratio and decreased ADF and NDF ratios of silage samples. The greatest relative feed value was obtained from 15 kg N da(-1) treatment It was concluded based on present findings that besides the nitrogen doses, nitrogen sources also significantly improved yield

EFFECTS OF HUMIC ACID, MICROBIOLOGICAL FERTILIZER AND PHOSPHATE ROCK ON YIELD AND YIELD COMPONENTS OF FIELD BEAN (PHASEOLUS VULGARIS L.)

Experiments were conducted over the experimental fields of Erciyes University with Goyniik 98 dry bean cultivar (Phaseolus vulgaris L.) in randomized blocks split-split plots experimental design with 4 replications during 2015 and 2016 growing seasons. Humic acid (HA) treatments (two applications, 2 kg da(-1)) were placed in main plots, microbial fertilizer (MF) treatments (two applications, phosphate-solubilizing Bacillus pumilus C26) were placed in subplots and phosphate rock (PR) treatments (4 applications, 29.3% P2O5, 0, 7.5, 15 and 22.5 kg da(-1)) were placed in sub-subplots. Plant and soil samples were taken from the experimental plots for the analyses of yield and yield components. HA, MF and PR treatments had different effects on investigated parameters of dry beans. As the average of the years, plant heights, the first pod heights, number of pods per plant, number of seeds per plant, number of seeds per pod, seed yield, harvest index values, biological yields, hundred-seed weights and seed protein ratios varied respectively between 42.95-53.65 cm, 10.16-13.90 cm, 13.85-24.85, 38.64-59.83, 2.36-3.16, 173.8-314.3 kg da(-1), 31.25-39.73%, 274.4-382.0 kg da(-1), 38.92-43.10 g and 22.93-24.94%. The greatest yield was obtained from the greatest phosphate rock dose applied together with humic acid and microbial fertilizer. All treatments significantly increased seed yields as compared to the control group (173.8 kg da(-1)). It was concluded based on present findings that 22.5 kg da(-1) (29.3% P2O5) phosphate rock together with humic acid and microbial fertilizer could be recommended for both organic and conventional dry bean farming

Machine learning based mass prediction and discrimination of chickpea (Cicer arietinum L.) cultivars

© 2023, The Author(s), under exclusive licence to Springer Nature B.V.Chickpea is an important edible legume that can be grown in rain fed conditions. Image analysis and machine learning could be used for rapid and non-destructive determination of seed physical attributes and such techniques yield objective, accurate and reliable results. In this study, size, shape, and area attributes of 26 different chickpea cultivars were determined by image processing method, and color properties were determined by chromametric method, and machine learning algorithms (Multilayer Perceptron-MLP, Random Forest-RF, Support Vector Regression-SVR, and k-Nearest Neighbor-kNN, were used for mass prediction of chickpea seeds. Ilgaz and Çakır cultivars had the highest size and shape values, while İzmir and Sezenbey cultivars had the highest color attributes. Compactness (in horizontal orientation) had a positive correlation with the equivalent diameter (in vertical orientation) and elongation (in vertical orientation) (r = 0.99 for both parameters). Besides, a* had a high correlation with b* (r = 0.97). According to Euclidean distances, Akça–İnci and Damla–Işık cultivars were identified as the closest cultivars in terms of physical attributes. In PCA analysis, PC1 and PC2 explained 73.17% of the total variation. The PC1 included length, geometric mean diameter, volume and surface area, and the PC2 included roundness (in horizontal orientation), thickness, elongation (in horizontal orientation) and sphericity. RF and ML had successful results with the values of 0.8054 and 0.8043 for train-test split, and 0.8231 and 0.8142 for k-fold cross validation, respectively. Present findings revealed that texture image processing and machine learning could be used as an effective and inexpensive discrimination tool for chickpea seeds

Oral ixazomib-dexamethasone vs oral pomalidomide-dexamethasone for lenalidomide-refractory, proteasome inhibitor-exposed multiple myeloma: a randomized Phase 2 trial

Multiple myeloma (MM) patients typically receive several lines of combination therapy and first-line treatment commonly includes lenalidomide. As patients age, they become less tolerant to treatment, requiring convenient/tolerable/lenalidomide-free options. Carfilzomib and/or bortezomib-exposed/intolerant, lenalidomide-refractory MM patients with &gt;= 2 prior lines of therapy were randomized 3:2 to ixazomib-dexamethasone (ixa-dex) (n = 73) or pomalidomide-dexamethasone (pom-dex) (n = 49) until progression/toxicity. Median progression-free survival (mPFS) was 7.1 vs 4.8 months with ixa-dex vs pom-dex (HR 0.847, 95% CI 0.535-1.341, P = 0.477; median follow-up: 15.3 vs 17.3 months); there was no statistically significant difference between arms. In patients with 2 and &gt;= 3 prior lines of therapy, respectively, mPFS was 11.0 vs 5.7 months (HR 1.083, 95% CI 0.547-2.144) and 5.7 vs 3.7 months (HR 0.686, 95% CI 0.368-1.279). Among ixa-dex vs pom-dex patients, 69% vs 81% had Grade &gt;= 3 treatment-emergent adverse events (TEAEs), 51% vs 53% had serious TEAEs, 39% vs 36% had TEAEs leading to drug discontinuation, 44% vs 32% had TEAEs leading to dose reduction, and 13% vs 13% died on study. Quality of life was similar between arms and maintained during treatment. Ixa-dex represents an important lenalidomide-free, oral option for this heavily pretreated, lenalidomide-refractory, proteasome inhibitor-exposed population

Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial

Background Maintenance therapy following autologous stem cell transplantation (ASCT) can delay disease progression and prolong survival in patients with multiple myeloma. Ixazomib is ideally suited for maintenance therapy given its convenient once-weekly oral dosing and low toxicity profile. In this study, we aimed to determine the safety and efficacy of ixazomib as maintenance therapy following ASCT. Methods The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study took place in 167 clinical or hospital sites in 30 countries in Europe, the Middle East, Africa, Asia, and North and South America. Eligible participants were adults with a confirmed diagnosis of symptomatic multiple myeloma according to International Myeloma Working Group criteria who had achieved at least a partial response after undergoing standard-of-care induction therapy followed by high-dose melphalan (200 mg/m2) conditioning and single ASCT within 12 months of diagnosis. Patients were randomly assigned in a 3:2 ratio to oral ixazomib or matching placebo on days 1, 8, and 15 in 28-day cycles for 2 years following induction, high-dose therapy, and transplantation. The initial 3 mg dose was increased to 4 mg from cycle 5 if tolerated during cycles 1–4. Randomisation was stratified by induction regimen, pre-induction disease stage, and response post-transplantation. The primary endpoint was progression-free survival (PFS) by intention-to-treat analysis. Safety was assessed in all patients who received at least one dose of ixazomib or placebo, according to treatment actually received. This trial is registered with ClinicalTrials.gov, number NCT02181413, and follow-up is ongoing. Findings Between July 31, 2014, and March 14, 2016, 656 patients were enrolled and randomly assigned to receive ixazomib maintenance therapy (n=395) or placebo (n=261). With a median follow-up of 31 months (IQR 27·3–35·7), we observed a 28% reduction in the risk of progression or death with ixazomib versus placebo (median PFS 26·5 months [95% CI 23·7–33·8] vs 21·3 months [18·0–24·7]; hazard ratio 0·72, 95% CI 0·58–0·89; p=0·0023). No increase in second malignancies was noted with ixazomib therapy (12 [3%] patients) compared with placebo (eight [3%] patients) at the time of this analysis. 108 (27%) of 394 patients in the ixazomib group and 51 (20%) of 259 patients in the placebo group experienced serious adverse events. During the treatment period, one patient died in the ixazomib group and none died in the placebo group. Interpretation Ixazomib maintenance prolongs PFS and represents an additional option for post-transplant maintenance therapy in patients with newly diagnosed multiple myeloma. Funding Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company