The prognostic significance of minimal residual disease in adult Egyptian patients with precursor acute lymphoblastic leukemia

AbstractBackgroundMinimal residual disease (MRD) studies in adult acute lymphoblastic leukemia (ALL) give highly significant prognostic information superior to other standard criteria as age, gender and total leucocytic count (TLC) in distinguishing patients at high and low risk of relapse.ObjectivesWe aimed to determine the value of MRD monitoring by flowcytometry (FCM) in predicting outcome in adult Precursor ALL patients.Patients and methodsBone marrow (BM) samples were analyzed by 4-color FCM collected at diagnosis and after induction therapy (MRD1) to correlate MRD positivity with disease free survival (DFS) and overall survival (OS).ResultsStudy included 57 adult ALL patients (44 males and 13 females) with a median age of 22years (18–49). DFS showed no significant difference with age, gender and initial TLC (p=0.838, 0.888 and 0.743, respectively). Cumulative DFS at 2years was 34% for B-lineage ALL (n: 35) and 57% for T-lineage ALL (n: 18) (p=0.057). Cumulative DFS at 2years was 7% for MRD1 positive (high risk, HR) versus 57% for MRD1 negative patients (Low risk, LR) (p<0.001). Cumulative DFS at 2years was 29% for HR patients (n: 26) versus 55% for LR (n: 27) according to GMALL classification (p=0.064). Cumulative OS did not differ according to age, gender and TLC (p=0.526, 0.594 and 0.513, respectively). Cumulative OS at 2years was 36% for B ALL (n: 39) versus 77% for TALL (n: 18) (p=0.016) and was 49% for Philadelphia chromosome (Ph) negative patients versus 0% for Ph-positive patients (p<0.001). Regarding MRD1, OS at 2years was 18% for MRD1 HR (n: 17) versus 65% for MRD1 LR (n: 38) (p<0.001). OS was 35% for high-risk patients (n: 30) and 62% for low-risk patients (n: 27) classified according to GMALL risk stratification (p=0.017).ConclusionMRD by FCM is a strong independent predictor of outcome in terms of DFS and OS and is a powerful informative parameter in guiding individual treatment in ALL patients

Prognostic utility of routine chimerism testing at 2 to 6 months after allogeneic hematopoietic cell transplantation.

The utility of routine chimerism analysis as a prognostic indicator of subsequent outcomes after allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning regimens remains controversial. To address this controversy, routine chimerism test results at 2 to 6 months after HCT with myeloablative conditioning regimens were evaluated for association with subsequent risk of chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, and overall mortality. Only 70 of 1304 patients (5%) had < 95% donor-derived cells in the marrow. Low donor chimerism in the marrow occurred more often in patients with low-risk diseases compared with those with higher-risk diseases and was significantly associated with a reduced risk of chronic GVHD. Among 673 patients evaluated, 164 (24%) had < 85% donor-derived T cells in the blood. Low donor T cell chimerism was more frequent in patients with low-risk diseases compared with those with higher-risk diseases, in those who received conditioning with busulfan compared with those who received conditioning with total body irradiation, and in those with lower-grade acute GVHD. Low donor T cell chimerism in the blood was significantly associated with a reduced risk of chronic GVHD but not with a reduced risk of relapse, NRM, or overall mortality. Routine testing of chimerism in the marrow and blood at 2 to 6 months after HCT with myeloablative conditioning regimens may be helpful in documenting engraftment in clinical trials, but provides only limited prognostic information in clinical practice

Effects of Oral Administration of Atorvastatin or Fenofibrate on Hyperlipidemia Induced by Betamethasone Dipropionate Injection in Rabbits

Betamethasone, a fluorinated and synthetic steroid, is a commonly used glucocorticoid. To our knowledge, no available studies exist concerning the hyperlipidemic effect of betamethasone dipropionate (BDP) in rabbits. Therefore, the current study was conducted to highlight the effects of intramuscular injection of BDP on lipid profile in rabbits, investigate the possible mechanism underlying the produced effects and evaluate the possible antihyperlipidemic effect of atorvastatin (ATR) and fenofibrate (FFB). For this purpose, twenty male New Zealand rabbits were classified into control, BDP (0.5 ml/kg B.wt/ IM/day/single dose), BDP+ATR; rabbits were IM injected with BDP, then they were orally given ATR (1.9 mg./kg. B.wt./ once/ day/ month) and group IV (BDP+FFB); rabbits were IM injected with BDP then they were orally given FFB (7.5 mg/kg B.wt/ once/ day/ month). The obtained result revealed that single IM injection of BDP produced a significant elevation in triglycerides, total cholesterol, LDL level with a significant decline in HDL in comparison to control group on the 3rd,7th,14th, 21st, 30th day of the experiment. On the 30th day of the experiment there was an increase in the ALT, AST, MDA, VCAM-1 as well as a significant decrease in TAC. Furthermore, BDP induced a significant increase in HMG-COA reductase gene expression and a significant decrease in lipoprotein lipase gene expression. Oral administration of ATR or FFB concurrently with BDP for a month succeeded in reducing the hyperlipidemia induced by BDP in rabbits

Multi-target action of Garcinia livingstonei extract and secondary metabolites against fatty acid synthase, α-glucosidase, and xanthine oxidase

Garcinia livingstonei is a traditional herbal medicine that showed beneficial health effects and bioactivities. Four compounds have been isolated from the plant leaves and were elucidated as lupeol, betulin, podocarpusflavone A, and amentoflavone. The inhibitory activities of G. livingstonei extract and isolated metabolites against fatty acid synthase (FAS), α-glucosidase, and xanthine oxidase (XO) were investigated in vitro. The affinity of the compounds toward the studied enzymes was investigated in silico. The plant extract inhibited FAS, α-glucosidase, and XO with IC50 values of 26.34, 67.88, and 33.05 µg/mL, respectively. Among the isolated metabolites, betulin exhibited the most inhibitory activity against α-glucosidase and XO with IC50 values of 38.96 and 30.94 µg/mL, respectively. Podocarpusflavone A and betulin were the most potent inhibitors of FAS with IC50 values of 24.08 and 27.96 µg/mL, respectively. Computational studies corroborated these results highlighting the interactions between metabolites and the enzymes. In conclusion, G. livingstonei and its constituents possess the potential to modulate enzymes involved in metabolism and oxidative stress

The First Report of Coxiella burnetii as a Potential Neglected Pathogen of Acute Hepatitis of Unknown Causes in Egypt

The World Health Organization (WHO) recently alerted the emergence of new pathogens causing acute hepatitis in children across several countries. This new situation directs us to the screening of neglected pathogens that cause acute hepatitis. Q-fever is a zoonotic disease, caused by Coxiella burnetii. Although a high seroprevalence of Coxiella burnetii was recorded in animals present in Egypt, Q-fever is still a neglected disease, and the diagnosis of Q-fever is not routinely performed in Egyptian hospitals. In this study, we performed a retrospective assessment for Coxiella burnetii in cases of hepatitis of unknown causes (HUC) enrolled in Assiut University hospitals, in Egypt. Out of 64 samples of HUC, 54 samples were negative for all hepatitis markers, labeled as acute hepatitis of unknown etiology (AHUE), and 10 samples tested positive for adenovirus and Hepatitis E virus (HEV). Q-fever was detected in 3 out of 54 (5.6%) of AHUE, and one sample was confirmed as coinfection of HEV/Q-fever. Jaundice was the most common clinical symptom developed in the patients. In conclusion, Coxiella burnetii was found to be a potential cause of acute hepatitis in HUC. The diagnosis of Q-fever should be considered in acute hepatitis cases in Egyptian hospitals