This study aimed to investigate the association of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms with serum drug levels and toxicities after high-dose methotrexate (MTX) infusion. The study included 37 children with acute lymphoblastic leukemia or non-Hodgkin lymphoma. Serum MTX levels and toxicities of bone marrow, liver and kidney were analysed. Genotype analysis of the C677T and A1298C gene polymorphisms from genomic DNA of the subjects was performed by real-time PCR. Subjects with MTHFR polymorphism for C677T (CT, TT) had significantly higher MTX levels at 24 h (p = 0.009), and these genotypes did not seem to cause toxicity. Subjects with MTHFR polymorphism for A1298C (AC, CC) had significantly higher MTX levels at 48 h (p = 0.02), and had more grade III/IV anemia (p = 0.02), thrombocytopenia (p = 0.0001), elevated AST levels (p = 0.04) and frequent febrile neutropenic episodes (p = 0.004). The present study suggests that A1298C gene, but not C677T polymorphism is associated with MTX-related toxicity.
Dysregulation of microRNA (miRNA) expression contributes to the pathogenesis of several clinical conditions. The aim of this study is to evaluate the associations between miRNAs and childhood acute lymphoblastic leukemia (ALL) to discover their role in the course of the disease. Forty-three children with ALL and 14 age-matched healthy controls were included in the study. MicroRNA microarray expression profiling was used for peripheral blood and bone marrow samples. Aberrant miRNA expressions associated with the diagnosis and outcome were prospectively evaluated. Confirmation analysis was performed by real time RT-PCR. miR-128, miR-146a, miR-155, miR-181a, and miR-195 were significantly dysregulated in ALL patients at day 0. Following a six-month treatment period, the change in miRNA levels was determined by real time RT-PCR and expression of miR-146a, miR-155, miR-181a, and miR-195 significantly decreased. To conclude, these miRNAs not only may be used as biomarkers in diagnosis of ALL and monitoring the disease but also provide new insights into the potential roles of them in leukemogenesis.
Haematopoietic stem cell transplantation (HSCT) remains the best therapeutic option for many acquired and inherited paediatric haematological disorders. Unfortunately, the probability of finding an HLA matched donor is limited. An alternative technique is PGD combined with HLA matching, which offers the possibility of selecting unaffected embryos that are HLA compatible with the sick child, with the aim of possible use of stem cells from the resulting baby in future. Since the first successful report for Fanconi anaemia a decade ago, the therapeutic success of this technique was reported in a few cases and for a limited number of disorders. Here, we report full recovery of 44 sick children who received HSCT from healthy infants conceived after pre-implantation HLA matching for the following 10 indications; beta-thalassaemia, Wiskott-Aldrich syndrome, Fanconi anaemia, sickle cell anaemia, acute myeloid leukaemia, acute lymphoblastic leukaemia, Glanzmann's thrombasthaenia, Diamond-Blackfan anaemia, X-linked adrenoleukodystrophy and mucopolysaccharidosis type I. No serious complications were observed among recipients and donors. Graft failure occurred in four children with beta-thalassaemia where a second HSCT was planned. Preimplantation HLA matching is a reliable technique and provides a realistic option for couples seeking treatment for an affected child when no HLA-matched donor is available.
This descriptive and case-control study was carried out in a pediatric oncology outpatient clinic to determine the school-related physical, social, and psychological problems and problems experienced in academic achievement of children treated for cancer. The sample of the study consisted of 56 Turkish patients with cancer, aged 7-18 years, who were in remission and attending school as well as their parents, a control group of patients who did not have cancer, and their teachers. A Child Information Form, a Child Health Questionnaire Parent's Form of 50 questions, a Behavior Evaluation Scale for Children, and Young People and a Teacher's Report Form were used as data collection tools in the study. Of the children, 30.3% experienced various physical difficulties stemming from cancer therapy that affected their school life. The number of late enrollments, the number of children repeating a grade, and the rates of school absenteeism were also found to be higher in the survivors than in the controls.
Objective: The aim of this study is to determine the frequency of dental anomalies (DAs) (microdontia, hypodontia, hyperdontia, enamel defect, root malformation) in pediatric cancer patients at the ages <5 years and between 5 and 7 years, and understand their relationship with the received therapy. Materials and Methods: Pediatric patients who were diagnosed with cancer and treated before the age of 7 years were investigated in a case- control design. The study included 93 pediatric patients whose ages at diagnosis were between 9 months and 7 years and whose treatments were completed before 5-8 years. Group A consisted of patients in the age range of 9 months to 4 years and Group B consisted of patients in the age range of 5-7 years. Seventy-two siblings with compatible dental age ranges were included in the control group. For both groups, intraoral examinations were performed and panoramic radiographs were taken. Results: Among the 93 pediatric patients, the mean age was 9.54±1.25 (range: 8-13 years) and 48 (51.6%) patients were male. The most common diagnosis was hematologic malignancy with a rate of 65.5%. At least one DA was detected in 7 (9.7%) individuals of the control group and in 78 (83.9%) of the patient group. While the patients in the study group had all kinds of DAs, those in the control group had only enamel defects. The rates of microdontia (p=0.077) and hypodontia (p=0.058) were detected to be significantly higher in Group A than in Group B. Root malformation was more common in patients receiving chemotherapy and radiotherapy than in those receiving only chemotherapy (p=0.006). Conclusion: In this study it was found that the pediatric patients who received cancer treatment before the age of 7 years constituted a high-risk group for DAs. The frequencies of microdontia and hypodontia were increased even more when the patient was treated for cancer before 5 years of age.
GVHD is the most common and well-known cause of morbidity and mortality following allogeneic BM transplantation. The GVHD following OLT is an uncommon complication but has a high mortality and poses a major diagnostic and therapeutic challenge. We herein discussed a 12-month-old girl with multi-system LCH, who developed end-stage liver disease despite intensive chemotherapy. She underwent ABO-compatible liver transplantation at 28 months while in remission from LCH. The donor was her 26-yr-old father. Post-operative course was uneventful. The GVHD manifested with skin rash and BM suppression on post-transplant day 94 and confirmed by both microchimerism and skin biopsy. Prednisolone, basiliximab, and ATG were administered immediately but the bone marrow suppression was not improved and the patient died because of Candida sepsis at six-month post-transplant. GVHD after OLT should be keep in mind in patients with rash and BM suppression after liver transplantation. In LDLT, a patient who carries risk factors should investigated for optimal HLA matching.
Human telomerase reverse transcriptase (hTERT) is the catalytic component of telomerase enzyme and has been shown to be associated with telomerase activity (TA). Although many studies in adult leukemia have established the importance of TA, very few have been reported in the children. In this study hTERT levels in childhood leukemia was evaluated and compared with the prognostic factors described before. The LightCycler instrument was used (online real-time PCR) for the quantification of hTERT in peripheral blood and bone marrow in 23 cases with acute lymphoblastic leukemia (ALL) and in 8 cases with acute myeloblastic leukemia (AML). Ten cases with normal peripheral blood (PB) and bone marrow (BM) were selected as control group. Cytogenetic analyses were available in 21 patients with leukemia. In all cases with acute leukemia and in control group, peripheral blood (PB) hTERT levels correlated significantly with bone marrow (BM) hTERT levels. Before treatment, patients with ALL had significantly higher hTERT levels than that of AML patients and control cases. Among patients with ALL, higher hTERT levels were observed in patients with pre-B leukemia, followed by B cell and T cell leukemia patients. Initially increased hTERT levels decreased to the nearly normal levels during remission in cases with ALL. No correlation was observed between the initial hTERT levels and the known prognostic factors except cytogenetic findings. Higher hTERT levels were detected in patients having karyotypic abnormalities which indicate poor prognosis. hTERT levels are significantly high in childhood ALL with the highest level of pre-B cell leukemia before treatment. Those high levels of hTERT decrease to almost normal levels in remission. hTERT levels might be useful in monitoring of leukemia in children.
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