Complete blood cells count abnormalities in COVID-19 patients and their prognostic significance: Single center study in Makkah, Saudi Arabia.

OBJECTIVES: To evaluate the role of different peripheral blood count parameters as a cheap and rapid test in determination of coronavirus disease -19 (COVID-19) severity and patients' outcome. METHODS: The data of 462 confirmed COVID-19 patients who attended at the Security Force Hospital, Makkah, Saudi Arabia, from October 2020 to March 2021 was retrospectively reviewed and C. Patients with viral infection and respiratory diseases other than COVID-19 were excluded from the study. Complete blood count parameters were compared in accordance with the severity of the clinical presentation, age, and disease outcome. RESULTS: A total of 277 (60%) were male and 185 (40%) female. Clinically, 32 (6.9%) had severe illness and 430 (93.1%) showed moderate clinical disease. Organ failure occurred in 2.8% of the patients. There was significant leucocytosis, neutrophilia, lymphopenia, high neutrophil-lymphocyte (N/L) ratio, and anemia in patients with severe COVID-19 diseases as well as in non-survivors' cases (p<0.001). Similarly, the inflammatory markers (C-reactive protein [CRP] and serum ferritin) were significantly elevated in the above-mentioned 2 groups (p<0.001). Significant decrease of the platelets count was detectable in clinically severe cases and non-survivors (p<0.01). Older age (>60 years) was associated with high leucocyte, neutrophil count, lymphopenia, anemia, organ failure, and poor outcome. CONCLUSION: Leucocytosis, neutrophilia, lymphopenia, and high N/L ratio together with elevated serum level of ferritin and CRP are eminent features of COVID-19 severity. The inclusion of these parameters in the regimens for patients' categorization on admission will enable early effective intervention and proper decision making during clinical case management.

Prognostic relevance of combined IDH1 and NPM1 mutations in the intermediate cytogenetic de novo acute myeloid leukemia.

Despite the great advance in treatment, cytogenetically normal Acute myeloid leukemia (CN-AML) is still a challenging entity. The discovery of IDH1 mutation in AML together with the frequent co-mutations; NPM1 and FLT3-ITD throughs a new insight into the pathogenesis and outcome of CN-AML. Recently, there has been an increasing number of recurring mutations in other genes for which the forecasting effect is still required. Despite the large number of risk variables established, there are relatively few prognostic indicators that can help in treatment decisions in AML patients. This study aimed at recording the frequency of IDH1 and NPM1 mutations in newly diagnosed AML and, dual clinicopathological significance. IDH1 and NPM1 mutations were analyzed using High-Resolution Melting curve analysis PCR in 78 newly diagnosed AML patients; 30 pediatric and 48 adult AML patients. IDH1 mutation was detected in 6 out of the 48 adult AML cases (12.5%) and all of them had intermediate cytogenetic prognostic stratification. 5/6 mutant IDH1 patients showed NPM1 co-mutation (P-value= 0.008). Mutant IDH1 patients showed significant resistance to induction therapy (P-value <0.001) and even those who achieved complete remission were relapsed later. Within the intermediate cytogenetic group, the IDH1 mutated patients had short overall survival (HR 12.9, 95% CI (3.1- 53.45) and event-free survival (HR 15.7, 95% CI (2.99-82.72) and P-value <0.001). IDH1 mutation is closely linked to the intermediate cytogenetic stratified group and in particular old age patients and has a great impact on their survival.

Absolute Monocyte Count is Superior than Absolute Lymphocyte Count at Day 28 as an Independent Prognostic Factor in Acute Myeloid Leukemia.

Leukemia is one of leading causes of death despite the significant improvement of survival. This study aimed at assessing the impact of absolute monocytic count (AMC), and absolute lymphocytic count (ALC) recovery on overall survival (OS) and leukemia free survival (LFS) in AML. 83 de novo AML cases were enrolled in this study. The hemogram parameters including differential leukocyte counts were determined and collected sequentially at days 1, 14, 21 and 28. There was no significant difference regarding AMC or ALC at any time points in relation to the cytogenetics prognostic groups. High AMC ≥ 0.8 × 109/L at day 28 was associated with shorter OS and LFS, P value 0.012 and 0.003 respectively. On multivariate models, high AMC was shown as an independent prognostic factor associated with poor OS and LFS (HR 3, 95% CI 1.1-8.1 and P value 0.02) and (HR 5, 95% CI 1.5-17.4 and P value 0.01) respectively. High ALC-D28 (≥ 0.35 × 109/L) was associated with prolonged OS and LFS survival, P value 0.032 and 0.016 respectively. However, it failed to prove the same significance using multivariate analysis. It was concluded that low AMC is an emerging independent predictor of better outcome in AML.

Evaluation of prothrombin induced by vitamin K absence, macrophage migration inhibitory factor and Golgi protein-73 versus alpha fetoprotein for hepatocellular carcinoma diagnosis and surveillance.

Hepatocellular carcinoma (HCC) represents a challenging malignancy of worldwide importance. It is the third most common cause of cancer-related death globally as most patients present with unresectable disease. Alpha-fetoprotein (AFP) is the widely and solely used biomarker for HCC diagnosis; yet, its usefulness is hampered by low sensitivity and specificity. We aimed to identify more sensitive biomarkers for HCC diagnosis and a surveillance algorithm that may facilitate early detection of HCC. A total of 305 Egyptian and Saudi participants grouped as healthy controls, cancer controls, benign hepatic lesions, chronic viral hepatitis and HCC were included. Serum AFP, prothrombin induced by vitamin K absence-II (PIVKA-II), macrophage migration inhibitory factor (MIF) and Golgi protein-73 (GP-73) levels were quantitated by enzyme immunoassay. Significantly higher levels of GP-73 and PIVKA-II were detected in the HCC group than in all other groups, while MIF showed a highly significant increase in HCC from all groups except the cancer control group. The HCC group showed no significant difference between the studied biomarkers and the type of chronic viral hepatitis. On the basis of multiple ROC curve analyses, GP-73 and PIVKA-II showed the highest sensitivity and specificity for surveillance and diagnosis. In conclusion, PIVKA-II and GP-73 offer an effective approach for early HCC diagnosis and surveillance of high-risk groups with a higher accuracy than AFP. MIF may serve as a promising screening tumor marker for the detection of gastrointestinal tract (GIT) malignancy.

Bone marrow T-cell percentage: A novel prognostic indicator in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive malignancy for which overall disease-free survival is less than 50%. Manipulation of the immune system is an interesting and promising therapy for AML patients. We aimed to characterize the immune system of AML patients, highlighting the clinical relevance of total bone marrow (BM) lymphocytes and subpopulations. Sixty-six new AML cases diagnosed according to WHO criteria from King Abdullah Medical City, KSA, from October 2012 to February 2015. Analysis of BM lymphocytes and subpopulations was done by flowcytometry. Significantly, high percentages of BM lymphocytes, T cells, and natural killer (NK) cells were detected in the group that achieved complete remission (P values = 0.004, <0.001, and <0.001, respectively). Overall survival (OS) was significantly prolonged in patients with high BM lymphocytes and T cells (P values = 0.047 and P 0.002, respectively). Multivariate analysis indicated that BM T-cell percentage and cytogenetics were independent prognostic factors predictive of OS (HR 4.7, P value = 0.011). BM T-cell percentage constitutes a novel host factor that can be used in combination with cytogenetics to better predict OS. Large-scale multicenter studies are recommended to clarify its role as a predictor of OS and leukemia-free survival.

Expression of P-glycoprotein, Cyclin D1 and Ki-67 in Acute Lymphoblastic Leukemia: Relation with Induction Chemotherapy and Overall Survival.

Previous studies showed that non-cycling cells have a higher multidrug resistance (MDR) expression, which may be down-regulated by proliferation induction. Triggering these cells into proliferation down-regulates high MDR expression. The aim of this study was to determine the expression of P-glycoprotein (PGP) and cell cycle parameters (cyclin D1 and Ki-67) in acute lymphoblastic leukemia (ALL) at diagnosis, and to evaluate the correlation between the expressions of each marker, and the clinical significance of such expression with response to induction chemotherapy and overall survival. A total of 78 newly diagnosed ALL patients were enrolled in our study. PGP, cyclin D1 and Ki-67 were determined by flow cytometry. PGP expression was encountered in 10/78 (12.8%) of ALL cases. Cyclin D1 and Ki-67 were expressed in 16/77 (20.6%) and 27/76 (34.6%) of ALL cases, respectively. None of the parameters were associated with response to induction chemotherapy and overall survival. Based on the current analysis, we conclude that a joint immunophenotypic evaluation of PGP and cell cycle parameters like that adopted in this study is unlikely to reveal mechanisms of multidrug resistance associated with the clinical outcome.