Our study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients’ clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children’s Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.
Background:The survival of children with acute lymphoblastic leukemia (ALL) has greatly improved in recent decades. Aim: We aimed at evaluating the outcome of children with ALL and their prognostic factors. Materials & Methods: A prospective study included 200 newly diagnosed pediatric ALL patients from 2009 to 2017. All patients were treated according to the modified total therapy study XIIIB for higher risk ALL adopted from St. Jude Children's Research hospital (SJCRH), USA. Results: Favorable age (< 10 y) and total leucocytic count (TLC) (≥ 50x10 9 /L) occurred in 75% and 69%, respectively. B-precursor ALL represented 82.5%. Central nervous system (CNS) involvement occurred in 4.5%. High-risk patients represented 47%. Complete remission was achieved in 92.5% and was significantly affected by the early morphologic response of BM d15, while it wasn't related to the phenotype. Eightyear overall survival, disease-free survival, and event-free survival were 77 ± 3%, 70 ± 4%, and 66 ± 3%, respectively. Adverse events included induction deaths (4.5 %), refractory leukemia (3%), relapse (23.2%), secondary AML (0.5%), and deaths in remission (3.5%). By multivariate analysis, unfavorable age group ≥ 10 years, hyperleukocytosis, and patients with slow early response were the only ones associated with unfavorable impact on the outcome. There was statistical significant difference between standard and high risk for B-precursor ALL but not for Tprecursor ALL. Conclusion: We concluded that treating children with ALL through modified TXIIIB protocol improved the survival at our institute than previous and the early response to treatment has a strong implication on the outcome.
Background: Despite the treatment progress of acute leukemias, neurological complications (NCs) can occur and may have a detrimental impact on the outcome. Aim: To study the pattern and outcome of NCs occurring during treatment of pediatric acute leukemias in Upper Egypt and to study possible factors influencing their outcomes. Methods: Children with AL who developed NCs during treatment were included. Patients with central nervous system (CNS) infiltration at diagnosis and those with any neurological insults before diagnosis were excluded. Data were retrospectively collected from patient files and included NCs, their outcome, and possible associated factors. Results: Neurological complications occurred in 89 out of 537 (16.6%) reviewed patients. Age was ≥ 10 years in 47.2% of patients, acute lymphoblastic leukemia was the most common diagnosis (77.5%) and the majority (77.9%) were classified as high-risk. Almost half of the patients suffered from NCs during the induction phase of treatment. Motor deficits and seizures were the most frequent manifestations. Neurovascular causes and peripheral neuropathy constituted 27% and 21.3% of the etiology. Other causes included CNS relapse (19.1%), seizures due to systemic causes (13.5%), CNS infections (12.4%), and leukoencephalopathy (6.7%). The treatment phase and recovery time differed significantly according to the type of NCs. The outcome of NCs was complete recovery in 67.4% of the patients, incomplete recovery in 7.9%, and no recovery and death in 24.7%. The etiology of NCs was the only factor that had a significant correlation with the outcome of the patients. Conclusions: Neurological complications during treatment occur in a significant proportion of pediatric patients with acute leukemia in South Egypt. Neurovascular causes and peripheral neuropathy are the most common NCs, and CNS hemorrhage is the most fatal. Supportive measures for these NCs must be optimized to improve outcome.
Background: FMS-Like Tyrosine kinase 3 (FLT3) plays an important role in early stages of hematopoiesis. FLT3 stimulation enhances proliferation and reduces apoptosis. One potential mechanism of FLT3 involvement in leukemia is over expression of its wild type and its ligand. The FLT3 protein is highly expressed in most patients with AML. In patients with ALL, FLT3 protein is highly expressed in up to 50% of leukemic blasts. Here, we aimed to evaluate the frequency of FLT3 protein expression in pediatric patients with
Background: As the survival rates of pediatric malignancies increased, many survivors experienced various long-term effects. Cognitive dysfunction may be one of the hazardous late effects among this critical age group. This study aimed to evaluate the cognitive functions, brain volume, and risk factors affecting them among survivors of hematological malignancies. Methods: This case-control study was conducted on 68 survivors of hematological malignancies, with a mean follow-up period 2.1± 1.2 years (ranged from 1 to 6.2 years). Age and sex-matched 68 child were selected as a comparison group. Detailed clinical and therapeutic data were collected from patients’ records. Assessment of cognitive function was done using Arabic version of the Stanford-Binet Test (version IV). Quantitative volumetric assessment of the brain was done using the NeuroQuant study (NQ). Results: The cancer survivors showed significantly lower levels in IQ and their subitems than the control group. Brain atrophy was observed in the NQ impression in the majority of our survivors. AML survivors had significantly lower volumes of thalami, white matter, and hippocampus than other survivors. Many risk factors had a significantly adverse effect on different IQ subitems, such as radiotherapy (RTH), high cumulative doses of methotrexate (MTX), and prednisone. While low white matter volume (WMV) was observed with higher mean cumulative doses of MTX and anthracyclines. Conclusions: Survivors of pediatric hematological malignancies showed significant cognitive impairment, this can be attributed to neuronal degeneration (brain volume loss). RTH, high cumulative doses of MTX and steroids were the most prominent risk factors.
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