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.

Pharmacological Approaches in Neurofibromatosis Type 1-Associated Nervous System Tumors.

Neurofibromatosis type 1 is an autosomal dominant genetic disease and a common tumor predisposition syndrome that affects 1 in 3000 to 4000 patients in the USA. Although studies have been conducted to better understand and manage this disease, the underlying pathogenesis of neurofibromatosis type 1 has not been completely elucidated, and this disease is still associated with significant morbidity and mortality. Treatment options are limited to surgery with chemotherapy for tumors in cases of malignant transformation. In this review, we summarize the advances in the development of targeted pharmacological interventions for neurofibromatosis type 1 and related conditions.

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.

Macrophage Migration Inhibitory Factor and Malondialdehyde as Potential Predictors of Vascular Risk Complications in Type 2 Diabetes Mellitus: Cross-Sectional Case Control Study in Saudi Arabia.

Background. Malondialdehyde (MDA) has been implicated in the development of many acute inflammatory, autoimmune diseases as well as chronic inflammatory metabolic disorders. Involvement of inflammatory response and oxidative stress is currently suggested as a mechanism underlying development of diabetes and its complications. Objective. To evaluate the clinical utility of MDA, macrophage migration inhibitory factor (MIF), LDL-C/HDL-C, and TG/HDL-C ratio as noninvasive laboratory markers for prediction of T2DM vascular complications. Method. 63 Saudi T2DM patients and 16 age and sex matched controls were included. Serum MDA and MIF were assayed by thiobarbituric acid reactive substances and ELISA, respectively. TG/HDL-C and LDL-C/HDL-C ratios were calculated. Results. Uncontrolled DM patients had significantly higher levels of MDA, MIF, TG/HDL-C, and LDL-C/HDL-C ratios when compared with controlled DM patients and control group (p < 0.001). MDA had 100% sensitivity and 88% specificity. MIF showed 97% sensitivity and 100% specificity and LDL-C/HDL-C had 97% sensitivity and 95% specificity. Meanwhile, TG/HDL-C had the lowest sensitivity and specificity in identifying diabetic patients who would suffer from vascular complications. Conclusion. MDA, MIF, and LDL-C/HDL-C could be new predictors of metabolic disturbance which promote vascular complications in T2DM.

Clinical significance of co-expression of aberrant antigens in acute leukemia: a retrospective cohort study in Makah Al Mukaramah, Saudi Arabia.

BACKGROUND: Aberrant phenotypes in acute leukemia have variable frequency and their prognostic and predictive relevance is controversial, despite several reports of clinical significance. AIMS: To determine the prevalence of aberrant antigen expression in acute leukemia, assess clinical relevance and demonstrate immunophenotype-karyotype correlations. MATERIALS AND METHODS: A total of 73 (40 AML and 33 ALL) newly diagnosed acute leukemia cases presenting to KAMC, Kingdom of Saudi Arabia, were included. Diagnosis was based on WHO criteria and FAB classification. Immunophenotyping by flow cytometry, conventional karyotyping and fluorescence in situ hybridization for gene rearrangements were performed. RESULTS: Aberrant antigens were detected in 27/40 (67.5%) of AML and in 14/33 (42.4%) in ALL cases. There were statistically significant higher TLC in Ly+ AML than in Ly-AML (p=0.05) and significant higher blast count in ALL with aberrant antigens at presentation and day 14 (p=0.005, 0.046). There was no significant relation to clinical response, relapse free survival (RFS) or overall survival (p>0.05), but AML cases expressing ≥2 Ly antigens showed a lower median RFS than those expressing a single Ly antigen. In AML, CD 56 was expressed in 11/40. CD7 was expressed in 7/40, having a significant relation with an unfavorable cytogenetic pattern (p=0.046). CD4 was expressed in 5/40. CD19 was detected in 4/40 AML associated with M2 and t (8; 21). In ALL cases, CD33 was expressed in 7/33 and CD13 in 5/33. Regarding T Ag in B-ALL CD2 was expressed in 2 cases and CD56 in 3 cases. CONCLUSIONS: Aberrant antigen expression may be associated with adverse clinical data at presentation. AML cases expressing ≥2 Ly antigens may have shorter median RFS. No specific cytogenetic pattern is associated with aberrant antigen expression but individual antigens may be related to particular cytogenetic patterns. Immunophenotype-karyotype correlations need larger studies for confirmation.

Does HOXA9 Gene Expression in Egyptian Chronic Myelogenous Leukemia Patients Affect Disease Progression? A Retrospective Cohort Study.

OBJECTIVE: Chronic myelogenous leukemia (CML) is a clonal stem cell disease and is consistently associated with the BCR-ABL fusion gene. The chronic phase of the disease tends to pass into an accelerated phase and eventually leads to acute leukemia if left untreated. Oncoproteins necessary for leukemic transformation are both fundamentally and clinically relevant to identify as they might be new molecular targets for the development of specific anti-leukemic drugs. This study is an initial step to define the proportion of HOXA9 gene expression in some Egyptians with chronic-phase CML at diagnosis and to evaluate its relation with BCR-ABL expression and its clinical significance. MATERIALS AND METHODS: Sixty-two newly diagnosed CML patients (56 in chronic phase, 1 in accelerated phase, and 5 in blastic crises) were enrolled in the study. HOXA9 and BCR-ABL gene expressions were detected by one-step RT-PCR. ABL was chosen as a control gene to calculate HOXA9/ABL and BCR-ABL/ABL ratios from densitometric values of PCR product intensities. RESULTS: HOXA9 expression was encountered in 25/56 (44.6%) of newly diagnosed CML patients in the chronic phase. The median expression was 0.31 (range: 0.08-1.37) in relation to the ABL gene, with a higher frequency of expression in CML patients presenting with splenomegaly (p<0.001), high Sokal score (p<0.001), and BCR-ABL expression from the first round (p=0.004). No association could be detected with other clinical parameters, overall survival, or disease-free survival. CONCLUSION: HOXA9 expression is closely related to poor prognostic factors, but we could not demonstrate its relationship to patient survival. CONFLICT OF INTEREST: None declared.

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.

The diagnostic value of C-reactive protein, interleukin-8, and monocyte chemotactic protein in risk stratification of febrile neutropenic children with hematologic malignancies.

BACKGROUND AND AIM: Recent advances in febrile neutropenia have highlighted the value of risk stratification especially that it can have important implications in terms of management. We aimed to identify a serum marker that may help to stratify febrile neutropenic pediatric patients treated for hematologic malignancies at the time of first evaluation. Thus, C-reactive protein (CRP), interleukin-8 (IL-8), and monocyte chemotactic protein-1-alpha (MCP-1-alpha) were evaluated for their predictive and diagnostic relevance in febrile episodes of cancer patients. PATIENTS AND METHODS: Within 24 hours of fever, CRP, IL-8, and MCP-1 serum levels were measured and the levels of these markers were related to the clinical findings of the patients. For this purpose, we collected and analyzed clinical data of 85 fever episodes occurring in 76 patients with hematologic malignancies, presenting to the Department of Pediatric Oncology, National Cancer Institute, Cairo University, during a 6-month period. RESULTS: Neutropenic children with febrile episodes were classified into 2 groups, a group with unexplainable fever (group I, n=26) and another group with either blood culture positive, and/or fever periods with a documented clinical sepsis and/or local infection (group II, n=59). Clinically, local sites of infection were encountered in 39 cases (45.9%), whereas a positive blood culture was detected in 20 cases. CRP, IL-8, and MCP-1 levels were significantly lower in group I versus group II (P value <0.001). There were overlaps of values between groups. CRP > or =90 mg/L was significantly associated with chemotherapy-related neutropenia and fever owing to bacteremia (P=0.038). The sensitivity, specificity, negative and positive predictive values of CRP, MCP-1, and IL-8 were (70%, 73%, 51%, and 85%), (64%, 92%, 53%, and 95%), and (71%, 77%, 54%, and 88%), respectively. Combining 2 or 3 markers improved the diagnostic performance of these test, as 78% of group II had elevated 2 or 3 markers versus 16% of the group with no evident infection. CONCLUSIONS: Low levels of CRP, MCP-1, and IL-8 could identify patients with unexplainable fever; whereas, high levels of these markers were of help in the diagnosis of infectious episodes. A model combining more than 1 marker is recommended in the assessment of febrile neutropenia.