الفهرس 
ACQUIIRED APLASTIIC ANEMIIAOnly 14 pages are availabe for public view
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Abstract
A
cquired aplastic anemia (AA) is a bone marrow failure syndrome characterized by pancytopenia with a hypocellular bone marrow. Most cases of AA are idiopathic, although viral infections, medications, or other primary immune disorders are occasionally implicated. For many years, an immune-mediated pathogenesis has been postulated for AA because Immunosuppressive Therapy (IST) is often successful in the treatment of AA and bone marrow lymphocytes from AA patients can suppress normal bone marrow in vitro.
The disease manifestations are thought to result from destruction of hematopoietic stem cells by auto-reactive T-lymphocytes.
Several factors have been proposed as good markers that appear to reflect the immune pathophysiology of AA.
CD4+CD25+ regulatory T cells (Tregs) were believed to control development and progression of autoimmunity by suppressing autoreactive effector T cells, but little was known regarding the function of Tregs in AA.
The aim of this study was to explores the prevalence and natural history of T-regulatory cells in pediatric patients with sever aplastic anemia both at diagnosis and in follow up to determine their potential utility as a prognostic tool.
The present study was carried out on 22 newly diagnosed children and adolescent with sever Aplastic anemia attended Ain Shams University children hospital Hematology/Oncology outpatient clinic and bone marrow transplantation clinic or admitted to the inpatients’ ward and 20 healthy control subjects of comparable age and sex Ain - Shams University children hospital outpatient clinic during the period from September 2013 to March 2015.
The mean age among the studied patients was 9.59±4.69 years ranged from 2 to 18 years. 17 of them were males (77.3 %) and 5 were females (22.7%).
All studied patients were subjected to full history taking, complete clinical examination and anthropometric measurements. Laboratory investigations at diagnosis in the form of: complete blood count (CBC) with differential, absolute reticulocyte count, BM aspiration and trephine biopsy to exclude malignancy and to determine morphological abnormalities and overall cellularity, Conventional cytogenetic analysis for presence of chromosomal abnormalities, Peripheral blood chromosomal breakage analysis to exclude Fanconi anaemia, Viral screening for (HAV, HBV, HCV, HSV, EBV, CMV, HIV), CD55+ /CD59+ cells using flow cytometric analysis to detect PNH clones, Vitamin B12 and folate to exclude Megaloblastic anemia, Autoantibody screen: Anti nuclear antibody and anti-DNA antibody, HLA matching, Preipheral blood (T-reg) cells CD4+/CD25+ using flow cytometric analysis.
Patients with matched sibling donor were prepared to receive peripheral stem cell transplantation (PSCT) according to Ain Shams university BMT unit protocol of stem cell transplantation.
Patients without matched related donor have received Immunosuppressive therapy (ATG + CyA) according to Ain Shams university BMT unit protocol of IST.
To evaluate the response of therapy in treated group another complete blood count (CBC) with differential, absolute reticulocyte count, Preipheral blood (T-reg) cells CD4+/CD25+ using flow cytometric analysis were done six months after receiving the definitive treatment (BMT or IST).
Eight patients received PSCT, six patients received IST and eight patients died before starting treatment, some patients received CsA due to unavailability of ATG.
The results of the current study were as the following:
• There was no statistical difference between patients and controls as regard weight, height, BMI.
• None of the patients had family history of Aplastic anemia, 9.1 % had history of drug exposure in the form of (diclofenac and metamizole), 13.6 % had history of preceding hepatitis, 100% manifested with bleeding, 90.9 % manifested with pallor and 63.6 % manifested with fever.
• There was a highly significant decrease in mean values of all hematological parameters in patients than in control.
• There was a highly significant decrease in initial T-reg percentage in patients than in controls.
• Because of the small sample size statistical analysis of data after treatment couldn’t have been done for each treated group separate.
• Patients who received PSCT recovered completely.
• Patients who received IST; two of them showed complete response, one showed partial response and 3 failed to respond to treatment.
• There was a significant increase in T reg percentage after treatement than initial T-regs.
• There was still a significant decrease in T-reg percentage after treatement than in healthy control which indicate that T reg improved after treatement but didn’t reach normal value.
• There was a significant increase in WBC’s count, RBC’s count, Hb, Platelet count, retic, neutrophils, monocytes after treatement.
• There was no significant correlations between initial Tregs and initial BM cellularity.
• There were no significant correlations between Tregs and RBC’s, WBC’s, neutrophil, lymphocyte, monocyte, esinophils, basophils, Platelet, Absolute reticulocyte counts and Hb either initially or after treatment.
We concluded that Tregs may be involved in the immune-pathogenesis of aplastic anemia by protection of hematopoietic stem cells from immune destruction.