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Fungal infections constitute a significant challenge and continue to be a predominant cause of treatment failure in pediatric leukemia cases. Despite the implementation of antifungal prophylaxis, these infections contribute to approximately 20% of cases in children undergoing treatment for acute lymphoblastic leukemia (ALL). The aim of this study is to highlight the diagnostic and therapeutic challenges associated with invasive fungal infections (IFIs). We also present a review of the epidemiology, risk factors, treatment, and a clinical presentation of IFI in patients with ALL. This case report details the clinical course of confirmed Candida albicans (C. albicans) and Aspergillus spp. infections during the consolidation phase of ALL treatment in a 5-year-old pediatric patient. This male patient did not experience any complications until Day 28 of protocol II. Then, the patient's condition deteriorated. Blood culture detected the growth of C. albicans. Despite the implementation of targeted therapy, the boy's condition did not show improvement. The appearance of respiratory symptoms necessitated a computed tomography (CT) of the chest, which revealed multiple nodular densities atypical for C. albicans etiology. In spite of ongoing antifungal treatment, the lesions depicted in the CT scans showed no regression. A lung biopsy ultimately identified Aspergillus species as the source of the infection. Overcoming fungal infections poses a considerable challenge; therefore, an accurate diagnosis and the prompt initiation of targeted therapy are crucial in managing these infections in patients with leukemia. [ABSTRACT FROM AUTHOR]

Despite significant progress in the treatment of some types of cancer, high-grade gliomas (HGGs) remain a significant clinical problem. In the case of glioblastoma (GBM), the most common solid tumor of the central nervous system in adults, the average survival time from diagnosis is only 15–18 months, despite the use of intensive multimodal therapy. Chimeric antigen receptor (CAR)-expressing T cells, which have already been approved by the Food and Drug Administration for use in the treatment of certain hematologic malignancies, are a new, promising therapeutic option. However, the efficacy of CAR-T cells in solid tumors is lower due to the immunosuppressive tumor microenvironment (TME). Reprogramming the immunosuppressive TME toward a pro-inflammatory phenotype therefore seems particularly important because it may allow for increasing the effectiveness of CAR-T cells in the therapy of solid tumors. The following literature review aims to present the results of preclinical studies showing the possibilities of improving the efficacy of CAR-T in the TME of GBM by reprogramming the TME toward a pro-inflammatory phenotype. It may be achievable thanks to the use of CAR-T in a synergistic therapy in combination with oncolytic viruses, radiotherapy, or epigenetic inhibitors, as well as by supporting CAR-T cells crossing of the blood–brain barrier, normalizing impaired angiogenesis in the TME, improving CAR-T effector functions by cytokine signaling or by blocking/knocking out T-cell inhibitors, and modulating the microRNA expression. The use of CAR-T cells modified in this way in synergistic therapy could lead to the longer survival of patients with HGG by inducing an endogenous anti-tumor response. [ABSTRACT FROM AUTHOR]

Despite the better understanding of the molecular mechanisms contributing to the pathogenesis of acute myeloid leukemia (AML) and improved patient survival in recent years, AML therapy still remains a clinical challenge. For this reason, it is important to search for new therapies that will enable the achievement of remission. Recently, the Food and Drug Administration approved three mutant IDH (mIDH) inhibitors for the treatment of AML. However, the use of mIDH inhibitors in monotherapy usually leads to the development of resistance and the subsequent recurrence of the cancer, despite the initial effectiveness of the therapy. A complete understanding of the mechanisms by which IDH mutations influence the development of leukemia, as well as the processes that enable resistance to mIDH inhibitors, may significantly improve the efficacy of this therapy through the use of an appropriate synergistic approach. The aim of this literature review is to present the role of IDH1/IDH2 mutations in the pathogenesis of AML and the results of clinical trials using mIDH1/IDH2 inhibitors in AML and to discuss the challenges related to the use of mIDH1/IDH2 inhibitors in practice and future prospects related to the potential methods of overcoming resistance to these agents. [ABSTRACT FROM AUTHOR]

Neuroblastoma is the most common extracranial solid tumor found in childhood and is responsible for 15% of deaths among children with cancer. Although multimodal therapies focused on surgery, chemotherapy, radiotherapy, and stem cell transplants have favorable results in many cases, the use of conventional therapies has probably reached the limit their possibility. Almost half of the patients with neuroblastoma belong to the high-risk group. Patients in this group require a combination of several therapeutic approaches. It has been shown that various immunotherapies combined with conventional methods can work synergistically. Due to the development of such therapeutic methods, we present combinations and forms of combining immunotherapy, focusing on their mechanisms and benefits but also their limitations and potential side effects. [ABSTRACT FROM AUTHOR]

Introduction: 2p15p16.1 microdeletion syndrome was described for the first time in 2007. The size of the microdeletion is variable and encompasses several genes, like XPO1, USP34, BCL11A, REL, PAPOLG, PEX13, COMMD1, B3GNT2, and EHBP1. Features of the syndrome include short stature, microcephaly, hypotonia, psychomotor developmental delay, anomalies of the fingers of the upper and lower limbs, dysmorphic features like receding forehead, broad nasal bridge, telecanthus, ptosis, flat philtrum, small mouth with a high, narrow palate and everted lower lip. The precise genotype–phenotype correlation in 2p15 deletion syndrome is not understood. The aim of the study is to present the patient's medical history and the diagnostic process. Case Presentation: A boy aged 9 was admitted to the Genetic Outpatient Clinic due to dysmorphic features and mild mental retardation. Full lips, broad nasal root, very light hair, excessively developed subcutaneous tissue, joint laxity, postural defect, flat-valgus foot with sandal gap, brachydactyly, and problems with concentration, memory, and counting were found. Diagnosis was based on microarray testing, and copy-number variation analysis was performed using CytoScan 750K array. Genetic imbalance in the form of a deletion within the short arm of chromosome 2 in the 2p15 region (containing 50 kbp) was shown. The microdeletion covers 2 genes: USP34 and XPO1. Parents were not carriers of that mutation. Conclusion: The phenotypic features presented by the patient were reflected in the genetic test. 2p15 microdeletion syndrome is genetically heterogeneous with possible de novo occurrence, as in the presented case. The precise genotype–phenotype correlation in 2p15 deletion syndrome should be widely studied because in the literature there is mainly mentioned 2p15p16.1 syndrome. Even though 2p15 microdeletion syndrome is a rare discovery and its features are mainly mild, it is necessary to pay special attention to them to refer patients to genetic counseling to make an accurate diagnosis. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation has become a treatment option for otherwise non-curative conditions, both malignant and benign, affecting children and adults. Nevertheless, the latest research has been focusing extensively on transplantation from related and unrelated haploidentical donors, suitable for patients requiring emergent hematopoietic stem cell transplantation (HSCT) in the absence of an HLA-matched donor. Haploidentical HSCT (haplo-HSCT) can be an effective treatment for non-malignant pediatric disorders, such as primary immunodeficiencies or hemoglobinopathies, by enabling a much quicker selection of the appropriate donor for virtually all patients, low incidence of graft-versus-host disease (GVHD), and transplant-related mortality (TRM). Moreover, the outcomes of haplo-HSCT among children with hematological malignancies have improved radically. The most demanding tasks for clinicians are minimizing T-cell-mediated alloreactivity as well as early GVHD prevention. As a result, several T-cell depletion approaches, such as ex vivo T-cell depletion (TCD), and T-cell replete approaches, such as a combination of anti-thymocyte globulin (ATG), post-transplantation cyclophosphamide (PTCy), cyclosporine/tacrolimus, mycophenolate mofetil, or methotrexate, have been taken up. As more research is needed to establish the most beneficial form of therapy, haplo-HSCT is currently considered an alternative donor strategy for pediatric and adult patients with complications like viral and bacterial infections, invasive fungal disease, and GVHD. [ABSTRACT FROM AUTHOR]

Summary: The prognostic impact of PICALM::MLLT10 status in childhood leukaemia is not well described. Ten International Berlin Frankfurt Münster‐affiliated study groups and the Children's Oncology Group collaborated in this multicentre retrospective study. The presence of the PICALM::MLLT10 fusion gene was confirmed by fluorescence in situ hybridization and/or RNA sequencing at participating sites. Ninety‐eight children met the study criteria. T‐cell acute lymphoblastic leukaemia (T‐ALL) and acute myeloid leukaemia (AML) predominated 55 (56%) and 39 (40%) patients, respectively. Most patients received a chemotherapy regimen per their disease phenotype: 58% received an ALL regimen, 40% an AML regimen and 1% a hybrid regimen. Outcomes for children with PICALM::MLLT10 ALL were reasonable: 5‐year event‐free survival (EFS) 67% and 5‐year overall survival (OS) 76%, but children with PICALM::MLLT10 AML had poor outcomes: 5‐year EFS 22% and 5‐year OS 26%. Haematopoietic stem cell transplant (HSCT) did not result in a significant improvement in outcomes for PICALM::MLLT10 AML: 5‐year EFS 20% for those who received HSCT versus 23% for those who did not (p = 0.6) and 5‐year OS 37% versus 36% (p = 0.7). In summary, this study confirms that PICALM::MLLT10 AML is associated with a dismal prognosis and patients cannot be salvaged with HSCT; exploration of novel therapeutic options is warranted. [ABSTRACT FROM AUTHOR]