الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Chemotherapy induced neutropenia is considered to be a major limiting toxicity in acute leukemia treatment that result in disruption of the integrity of the gastrointestinal mucosa which increases the risk for invasive infection due to colonizing bacteria and/or fungi that translocate across intestinal mucosal surfaces damaged by cytotoxic therapy. Since the magnitude of the neutrophil-mediated component of the inflammatory response may be muted in neutropenic patients, a fever may be the earliest and only sign of infection. It is crucial to determine neutropenic fever early and to initiate empiric systemic antibacterial therapy promptly in order to avoid progression to a sepsis syndrome and possibly death.
Sepsis is a potentially fatal medical emergency characterized by a generalized response that occur due to release of proinflammatory mediators leading to inflammatory state (called a systemic inflammatory response syndrome or SIRS) that is triggered by an infection. It is considered one of the most common causes of complications and mortality during neutropenia after chemotherapy in acute leukemia patients.
Early detection of infection as well as early prediction of bad prognosis using serological markers can aid in early intervention and treatment of infectious condition and thus improvement of outcome of acute leukemia treatment and reduction of mortality during bone marrow aplasia.
Angiopoietin1 and Angiopoietin2 are part of a family of vascular growth factor that play a role in embryonic and postnatal life. Ang-1 stabilizes the endothelium, inhibits vascular leakage, and suppresses inflammatory and coagulation gene expression through constitutive activation of Tie-2,while Ang-2 promotes loss of barrier integrity, mediating proinflammatory and proangiogenic effects that result in vascular leak and organ dysfunction.
The aim of the present work was to evaluate the value of Ang-2 /Ang-1 ratio as a predictive factor for progression to septic shock in acute leukemia patients presented with febrile neutropenia, and its role as a biomarker for risk assessment for febrile neutropenia patients.
The study included 36 patients with acute leukemia, 29 patients were of AML subtypes and 7 patients were of ALL subtypes patients. The age of AL patients ranged from 18 to 72 years with a mean age of 41.14 ± 16.46.Twenty (55.6%) patients were males and 16 (44.4%) were females., subjects participating in this study were subjected to the following:
I- Thorough history taking.
II- Thorough clinical examination.
III- Routine work up:
- Renal function tests.
- Liver function tests.
- Complete blood picture (CBP).
- Radiological work up (chest X-ray, U/S abdomen &pelvis).
- Erythrocyte sedimentation rate (ESR).C-Reactive Protein(CRP)
- Electrolytes: Sodium (Na), Potassium(K).
- Prothrombin time (PT) with international normalized ratio (INR), Partial thromboplastin time (PTT).
- Blood culture.
IV- MASCC score.
V- Serum Angiopoetin-1 and Angiopetin-2 by Enzyme linked immunoassay (ELISA).
VI- Diagnostic laboratory investigations:
a- Bone marrow examination.
b- Immunophenotyping.
c- Advanced investigations
The following results were obtained
1. 19 out of 36 patients had uncomplicated febrile neutropenia( group (A)) and 17 patients out of 36 their febrile neutropenia were complicated with septic shock( group(B)).
2. 35% of patients with febrile neutropenia who developed septic shock (group (B))has a comorbid condition, There was a statically significant difference regarding occurrence of septic shock and presence of co morbid conditions (P value=(0.037*))
3. MASCC score was lower in patients with complicated febrile neutropenia and there was a statistically significant difference between the two groups regarding MASCC score (p value=0.001).
4. There was no statistically significant difference between the two groups of patients regarding hematological profile, liver function tests, kidney function tests, coagulation profile and ESR.
5. The positivity of blood culture is more common in septic shock group of patients. There was statistically significant difference between the two groups regarding blood culture positivity. (P value=0.048).
6. CRP level was higher in septic shock group of patients and there was a there was a statistically significant difference between the two groups of patients regarding CRP. (P value=0.006)
7. Angiopoitin2 level was higher in FN patients that developed septic shock compared to patients with non –complicated FN while Angiopoitin 1 was lower in in FN patients that developed septic shock compared to patients with non –complicated FN
8. Angiopoitin 2/Angiopoitin1 ratio was higher in FN patients who developed septic shock compared to patients with non –complicated FN.There was a statically significant difference between the two groups regarding angiopoitin2/angiopoitin1ratio (p value =(<0.001)).
9. There was no statistically significant correlation between sex and age of the cases and angiopotien1,angiopotin2 and Angio2/Angio1 ratio
10. There was a moderate positive correlation between CRP and Angiopoitin/Angiopoitin1 ratio.that means the higher the CRP level, the higher the Angiopoitin/Angiopoitin1 ratio.
11. There was a moderate negative correlation between angiopoitin2 and MASCC score additionally there was a moderate positive correlation between angiopoitin1 and MASCC score.
12. ROC curve analysis was performed and it showed that certain Angio2/Angio1 ratio (more than 10) would be considered as a level that could predict sepsis in febrile neutropenic patients. (Area under the curve (AUC) = 0.854, represents the overall accuracy of this value in predicting septic shock with a specificity of 89.47 and a sensitivity of 70.59.