Cytochromes P450 (CYPs) play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75% of the total metabolism of commercially available drugs, including chemotherapeutics. The gene expression and enzyme activity of CYPs are variable between individuals, which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics, as well as differences in the efficacy and toxicity of clinically used drugs. This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients, as well as the clinical outcome after receiving cyclophosphamide chemotherapy. DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex- and age-matched healthy individuals. The presence of the CYP2B6*9 (G516T) polymorphism was examined by PCR-based allele specific amplification (ASA). Patients were further indicated for receiving chemotherapy, and then they were followed up. The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models, comprising allelic (T-allele vs. G-allele, OR = 4.8, p < 0.001) and dominant (GT + TT vs. GG, OR = 5.4, p < 0.001) models. Following cyclophosphamide chemotherapy, we found that the patients with variant genotypes (GT + TT) were less likely to achieve remission compared to those with the wild-type genotype (GG), with a response percentage of (37.5% vs. 83%, respectively). In conclusion, our findings showed that the CYP2B6*9 (G516T) polymorphism is associated with B-CLL susceptibility among Egyptian patients. This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.

Chemotherapy remains foundational to oncology, yet treatment response, resistance, and gastrointestinal toxicity vary widely between patients in ways that tumor stage, molecular subtype, and host pharmacogenomics do not fully explain. The gut microbiome contributes to this variability through two primary mechanisms: direct biotransformation and bioaccumulation of cytotoxic agents by microbial enzymes, and indirect modification of epithelial barrier integrity, inflammatory tone, and ecological resilience after cytotoxic injury. We propose precision pharmacomicrobiomic conditioning: the drug-specific, timing-anchored preservation or reshaping of microbial function before and during chemotherapy, which is distinguished from generic microbiome modulation by its linkage to a defined pharmacologic and toxicity profile. We operationalize this concept through two original constructs: five-archetype baseline risk classification stratifying patients by microbial enzymatic, inflammatory, ecological, and recovery phenotypes; and a three-phase clinical workflow specifying the assay, time point, and decision rule from pre-treatment stratification through adaptive longitudinal monitoring. These constructs are proposed strictly for prospective validation and are not presented as clinically validated decision tools. Furthermore, while dynamic functional and metabolic biomarkers may have higher predictive value than static, single bacterial taxa, this hypothesis requires rigorous confirmation in sufficiently powered, externally validated clinical cohorts. We conclude with the minimum reporting standards required to test these constructs: chemotherapy exposure metrics, toxicity grading versions, functional and strain-level profiling, and engraftment endpoints, and position microbiome profiling as an additional stratification layer integrated with pharmacogenomics and conventional clinical predictors, not as independent grounds for dose modification. Currently, no microbiome-derived biomarker has undergone prospective validation or received regulatory approval for standard chemotherapy stratification.

Background: Approximately 75% of drug metabolism in clinical settings is attributed to cytochrome P450 enzymes. This study aimed to assess the effects of the CYP3A4*1B and CYP3A5*3 genetic variations on the clinical results of individuals with chronic lymphocytic leukemia (CLL) following cyclophosphamide treatment. Furthermore, we aimed to ascertain how well the inflammatory condition affects the therapeutic response. Methods: CYP3A4*1B and CYP3A5*3 polymorphisms were examined in 150 Egyptian CLL patients using allele-specific amplification (ASA)-polymerase chain reaction (PCR); serum interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were also measured to assess the non-genetic inflammatory effect on CYP3A4 and CYP3A5 genes. Patients further received chemotherapy and were subsequently followed up. Results: The allelic frequencies of the CYP3A4*1B gene were (74.3% A-allele vs. 25.7% G-allele), and for CYP3A5*3, these frequencies were (73.4% A-allele vs. 26.6% G-allele). Patients with the CYP3A4*1B and CYP3A5*3 genes, or both variants, were less likely to respond than the normal patients (p < 0.001). Regarding the non-genetic inflammatory effect, patients in the response group who achieved partial remission were characterized by higher IL-6 and TNF-α values than those who achieved complete remission (p < 0.001), and patients in the non-response group who had a progressive disease were characterized by higher IL-6 and TNF-α values than those who had a stable disease (p < 0.001). Conclusion: CYP3A4*1B and CYP3A5*3 variants could be helpful indicators in predicting the response to cyclophosphamide chemotherapy. CYP3A4 and CYP3A5 variability should be factored into personalized medicine, which attempts to optimize drug dosing for individual patients by considering genetic and non-genetic factors affecting the response.

Background: Chronic lymphocytic leukemia (CLL) is a malignant disease of the blood characterized by the proliferation of mature B-lymphocytes in the bone marrow and lymphoid tissues. The altered functions of innate immune elements and adaptive immune factors are interconnected in CLL and are decisive for its onset, evolution, and therapeutic response. This study aimed to investigate the correlation between serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels and outcomes in CLL. Patients and methods: Serum IL-6 and TNF-α levels were measured by enzyme-linked immunosorbent assay from 100 Egyptian patients newly diagnosed with CLL and 100 age-matched and sex-matched healthy individuals. Cytokine levels were correlated with clinical features and the response after receiving chemotherapy. Results: Serum IL-6 and TNF-α levels were significantly higher in CLL patients than controls (median, 49 vs. 6.2 ng/l and median, 38.5 vs. 4.16 ng/l, respectively). A significant association was found between IL-6 and TNF-α levels and abnormal karyotyping, advanced disease stage, higher white blood cells, lymphocyte count, β2 microglobulin, and lactate dehydrogenase concentrations (P<0.001 for each). No significant difference between the responder and nonresponder patients after receiving chemotherapy was noticed regarding both IL-6 and TNF-α levels. Conclusion: Serum IL-6 and TNF-α levels were correlated with advanced CLL stage and worse prognosis but were related to the patient’s outcome after receiving chemotherapy.