Comparison of a modified pediatric protocol versus a hyper-CVAD protocol in adolescents and young adults with Philadelphia-negative acute lymphoblastic leukemia: A multicenter retrospective analysis.

BACKGROUND: The outcomes of Pediatric acute lymphoblastic leukemia (ALL) have improved dramatically whereas outcomes for ALL amongst adolescents and young adults (AYA) have lagged behind. The introduction of pediatric-like regimens to manage adult ALL has shown promising outcomes across several analyses. MATERIALS AND METHODS: In this analysis, we aimed to retrospectively compare the differences in outcomes among patients aged 14-40 years with Philadelphia-negative ALL treated with a Hyper-CVAD protocol versus a modified pediatric protocol. RESULTS: A total of 103 patients were identified with 58 (56.3%) in the modified ABFM group and 45 (43.7%) in the hyper-CVAD group. The median duration of follow-up for the cohort was 39 months (range 1-93). There were significantly lower rates of MRD persistence after consolidation (10.3% vs. 26.7%, P = 0.031) and transplantation (15.5% vs. 46.6%, P < 0.001) in the modified ABFM group. 5-year OS rates (83.9% vs. 65.3%, P = 0.036) and DFS rates (67.4% vs. 44%, P = 0.014) were higher in the modified ABFM groups. The incidence of grade 3 and 4 hepatotoxicity (24.1% vs. 13.3%, P < 0.001) and osteonecrosis (20.6% vs. 2.2%, P = 0.005) were higher in the modified ABFM group. CONCLUSION: Our analysis demonstrates that the use of a pediatric modified ABFM protocol demonstrated superior outcomes compared to the hyper-CVAD regimen in the treatment of Philadelphia-negative ALL amongst AYA patients. However, the modified ABFM protocol was associated with an increased risk of certain toxicities including high grade liver toxicity and osteonecrosis.

The Performance of Equations That Estimate Glomerular Filtration Rate against Measured Urinary Creatinine Clearance in Critically Ill Patients.

The performance of glomerular filtration rate- (GFR-) estimating equations was studied against creatinine clearance measured by 24-hour urine collection (CrCl24h-urine) in critically ill patients. Methods. In this substudy of the PermiT trial (https://clinicaltrials.gov/ct2/show/ISRCTN68144998), patients from King Abdulaziz Medical City-Riyadh who had CrCl24h-urine were included. We estimated GFR using Cockroft-Gault (CG), modification of diet in renal disease study (MDRD), chronic kidney disease epidemiology collaboration (CKD-EPI), and Jelliffe equations. For the CG equation, we entered the actual weight in one calculation (CGactual-wt), and if BMI ≥30 kg/m2, we entered the ideal body weight (CGideal-wt) and the adjusted body weight (CGadjusted-wt) in two calculations. We calculated the MDRD equation based on 4 (MDRD-4) and 6 variables (MDRD-6). The performance of these equations was assessed by different ways including Spearman correlation, bias (difference between estimated GFR and CrCl24h-urine), precision (standard deviation of bias), and Bland-Altman plot analysis. Results. The cohort consisted of 237 patients (age 45 ± 20 years, males 75%, mechanically ventilated 99% with serum creatinine 101 ± 94 µmol/L and CrCl24h-urine 108 ± 69 ml/min/1.73 m2). The correlations between the different equations and CrCl24h-urine were modest (r: 0.62 to 0.79; p < 0.0001). Bias was statistically significant for CGactual-wt (21 ml/min), CGadjusted-wt (12 ml/min), and MDRD-6 (-10 ml/min) equations. Precision ranged from 46 to 54 ml/min. The sensitivity of equations to correctly classify CrCl24h-urine 30-59.9 ml/min/1.73 m2 was 17.2% for CGactual-wt, 30.0% for CGideal-wt, 31.0% for CGadjusted-wt, 31.0% for MDRD-4, 39.1% for MDRD-6, 13.8% for CKD-EPI, and 34.5% for Jelliffe equation. Conclusions. Commonly used GFR-estimating equations had limited ability to properly estimate CrCl24h-urine and to correctly classify GFR into clinically relevant ranges that usually determine dosing of medications.