Nesma E. Abdelfattah

Genetic abnormalities provide diagnostic and prognostic information for pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. The aim of this study was to determine the effects of genetic CNAs and RUNX1 gene abnormalities on the outcome of pediatric BCP-ALL patients. This study included 78 de novo-BCP-ALL pediatric patients who presented to the Pediatric Oncology Department of the National Cancer Institute (NCI), Cairo University. We aimed to study the impact of copy number alteration (CNA) of 8 of the most altered genes in BCP-ALL patients, in addition to RUNX1 gene abnormalities, on patient survival and response to treatment. Multiplex ligation-dependent probe amplification (MLPA) was used to detect CNA, while RUNX1 gene alterations were detected by fluorescence in situ hybridization (FISH). CNA of the PAX5 gene was significantly associated with worse overall survival (OS) and event-free survival (EFS) (P = 0.012 and P = 0.025, respectively). An increase in the CNA of ETV6 was associated with an increase in minimal residual disease (MRD) on day 15 (P = 0.041). Although RUNX1 gene abnormalities were not a predictor of shorter OS or EFS, an interesting significant association was found between PAX5 CNA and RUNX1 gene gain and translocation (P = 0.017 and P = 0.041, respectively). PAX5 CNA is an adverse prognostic factor. ETV6 CNA is associated with high MRD on day 15.

Invasive candidiasis (IC) represents a growing concern worldwide, with a considerable increase in non-albicans Candida (NAC) species. The study's primary goal was to determine if species identification by semi-nested PCR (sn-PCR) with primers for the five most prevalent Candida species is sufficient to deal with the current trends of Candida infections in cancer patients. Over one year, Candida isolates were collected from samples of patients with hematological and solid organ tumors in a single center. Species of Candida were identified by chromagar and multiplex sn-PCR using specific primers for Candida albicans, Candida tropicalis, Candida glabrata, Candida krusei, and the Candida parapsilosis complex. Most Candida infection episodes are caused by NAC species (70.5% of 105 isolates). Rare species (14 isolates) accounted for 13.3% of isolates and were not identified by sn-PCR using the five most common Candida species primers. More than half of these rare species caused candidemia in cancer patients (57.1%; p = 0.011). The risk factor for candidiasis was recent surgeries (p = 0.020) in adults and chemotherapy in pediatric patients (p = 0.006). Prolonged hospitalization and genitourinary tract cancer were significantly associated with invasive infections (p = 0.005 and 0.049, respectively). Recent surgery was a significant risk factor associated with C. parapsilosis and C. glabrata infections (P = 0.038 and 0.003, respectively), while C. tropicalis was significantly more common in patients with hematological malignancies (P = 0.012). Techniques with a broader identification spectrum than the major five Candida species are crucial for the optimal management of cancer patients.

Candidemia is a life-threatening invasive fungal infection in immunocompromised patients. The widespread use of azoles and the shift toward non-albicans Candida (NAC) species remarkably increase azole resistance in developing countries. We aimed to study candidemia trends and associated risk factors in oncology patients since they vary geographically, and rapid and appropriate treatment improves outcomes. Vitek 2 was used to identify the Candida species, and the E-test determined their susceptibility to azoles. Candida was the cause of 3.1% (n = 53/1701) of bloodstream infections (BSIs) during a 1-year study. Candida tropicalis was the most predominant species among the 30 candidemia episodes studied (36.7%), followed by C. albicans (33.3%). However, C. krusei, C. guilliermondii, C. pelliculosa, C. parapsilosis, C. famata, and C. inconspicua accounted for 30.0% of the isolates. An increased risk of NAC BSI was significantly associated with chemotherapy and leucopenia (P = 0.036 and 0.016, respectively). However, the multivariable analysis revealed that leucopenia was the only independent risk factor (P = 0.048). Fluconazole and voriconazole resistance were 58.3% and 16.7%, with NAC species showing higher resistance rates than C. albicans. Both fluconazole and voriconazole minimum inhibitory concentration (MIC) median values were higher in NAC than in C. albicans, but only voriconazole was significantly higher (0.220 versus 0.048 μg/ml, P = 0.047). In conclusion, the increased prevalence of NAC BSIs and incredibly high fluconazole resistance rates in cancer patients emphasize the necessity of antifungal stewardship to preserve voriconazole effectiveness, continued surveillance of candidemia, and future studies into azole resistance molecular mechanisms.