Investigation of FANCA mutations in greek patients

Background: Fanconi anemia (FA) is a rare genetic disease characterized by considerable heterogeneity. Fifteen subtypes are currently recognised and deletions of the Fanconi anemia complementation group A (FANCA) gene account for more than 65% of FA cases. We report on the results from a cohort of 166 patients referred to the Department of Medical Genetics of Athens University for genetic investigation after the clinical suspicion of FA. Materials and Methods: For clastogen-induced chromosome damage, cultures were set up with the addition of mitomycin C (MMC) and diepoxybutane (DEB), respectively. Following a positive cytogenetic result, molecular analysis was performed to allow identification of causative mutations in the FANCA gene. Results: A total of 13/166 patients were diagnosed with FA and 8/13 belonged to the FA-A subtype. A novel point mutation was identified in exon 26 of FANCA gene. Conclusion: In our study 62% of FA patients were classified in the FA-A subtype and a point mutation in exon 26 was noted for the first time

Fulminant Aeromonas hydrophila infection during acute lymphoblastic leukemia treatment

Aeromonas hydrophila septicemia has a fulminant course and it has been usually reported in immunocompromised hosts and rarely among children with leukemia. High morbidity and mortality is associated with A hydrophila infections. We describe the case of a child with acute lymphoblastic leukemia who presented with septicemia due to A hydrophila. The patient presented with fever and skin discoloration during a febrile neutropenia episode, which rapidly evolved into bacteremia and extensive thigh suppuration, fasciitis, and myonecrosis. Apart from antibiotic treatment, surgical debridement to relieve compartment pressure and prevent further lower extremity compromise was promptly performed. Despite long delays in chemotherapy and an extensive tissue gap, primary closure of the involved area was possible with full cosmetic and functional limb recovery, and the patient has remained in clinical remission for more than 7 years

Invasive acremonium strictum infection in a bone marrow transplant recipient

We describe an invasive Acremonium strictum infection in a 9-year-old debilitated bone marrow transplant recipient. Outcome was successful, despite resistance to the amphotericin B that was initially administered. A. strictum was isolated from bone and urine cultures. We summarize data on 15 opportunistic invasive infections caused by Acremonium in pediatric hosts reported thus far in the English language literature

Melatonin and immunomodulation: Connections and potential clinical applications

Melatonin is the main hormone secreted by the pineal gland in the human brain. It has a strong impact on the sleep- wake cycle and is considered a general modulator of the human circadian rhythm. Apart from these well- established properties, melatonin possesses immunomodulatory, antioxidative and antiinflammatory properties. The potential ability of this hormone to act synergistically with several cytokines by enhancing their antitumoral activity and dramatically decreasing their adverse effects has placed melatonin among the new and promising agents in cancer immunotherapy. The use of the neurohormone alone or in combination with cytokines and traditional chemotherapeutic drugs is currently under vigorous investigation. Experimental and clinical trials have already depicted some of the immunomodulatory and antitumor effects of melatonin, delineating the need for further research in this field. Copyright (c) 2006 S. Karger AG, Basel

HEPATITIS C TREATMENT CONCOMITANT TO CHEMOTHERAPY AS “SALVAGE” THERAPY IN CHILDREN WITH HEMATOLOGIC MALIGNANCIES

In patients with malignancies, chronic hepatitis C reactivation or severe flare is uncommon and antiviral treatment is deferred mainly due to underlying bone marrow and immune suppression. We report the use of antiviral treatment concomitantly to chemotherapy in 3 children with hematologic malignancies, chronic hepatitis C, and significant liver dysfunction

The Prognostic Effect of CDKN2A/2B Gene Deletions in Pediatric Acute Lymphoblastic Leukemia (ALL): Independent Prognostic Significance in BFM-Based Protocols

One of the most frequent genes affected in pediatric ALL is the CDKN2A/2B gene, acting as a secondary cooperating event and playing an important role in cell-cycle regulation and chemosensitivity. Despite its inclusion in combined CNA (copy-number alterations) classifiers, like the IKZF1plus entity and the UKALL CNA profile, the prognostic impact of the individual gene deletions outside the context of a combined CNA evaluation remains controversial. Addressing the CDKN2A/2B deletions’ additive prognostic effect in current risk-stratification algorithms, we present a retrospective study of a Greek pediatric ALL cohort comprising 247 patients studied over a 24-year period (2000–2023). Herein, we provide insight regarding the correlation with disease features, MRD clearance, and independent prognostic significance for this ALL cohort treated with contemporary BFM-based treatment protocols. Within an extended follow-up time of 135 months, the presence of the CDKN2A/2B deletions (biallelic or monoallelic) was associated with inferior EFS rates (65.1% compared to 91.8% for the gene non-deleted subgroup, p p p p p = 0.947). The presence of the CDKN2A/2B deletions clearly correlated with inferior outcomes within all protocol-defined risk groups (standard risk (SR): EFS 66.7% vs. 100%, p p p p p < 0.001), respectively, designating the alteration’s independent prognostic significance in the context of modern risk stratification. The results of our study demonstrate that the presence of the CDKN2A/2B deletions can further stratify all existing risk groups, identifying patient subgroups with different outcomes. The above biallelic deletions could be incorporated into future risk-stratification algorithms, refining MRD-based stratification. In the era of targeted therapies, future prospective controlled clinical trials will further explore the possible use of cyclin-dependent kinase inhibitors (CDKIs) in CDKN2A/2B-affected ALL pediatric subgroups