الفهرس 
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Abstract
Acute myeloid leukemia (AML) is a heterogeneous disorder with treatment results much inferior to acute lymphoblastic leukemia. Treatment failure is largely attributed to the persistence of leukemia stem cells (LSCs) which are less accessible and hence less responsive to chemo-therapeutics. The classical LSCs phenotype is CD34+/CD38-; however LSCs express other markers especially CD123 and CD133 which may be even earlier than CD34. We hypothesized that that CD123 and CD133 may be better markers of LSCs and that the more the number of LSCs at diagnosis /and or at follow up periods, the more the case would be resistant to therapy. Purpose: The purpose of this study was to test the efficiency of various antibodies separately or in combinations to characterize LSCs and, if possible, to discriminate them from normal hematopoietic stem cells (HSCs). We aimed thereafter to demonstrate the impact of LSCs frequency at diagnosis and at follow up periods as compared to minimal residual disease (MRD) on overall survival (OS), disease free survival (DFS). We aimed lastly to study the relationship between MRD and LSCs frequency at follow up periods to verify which will be better correlated to outcome. Patient and Methods: The study was performed on 84 newly diagnosed AML patients including 51 Male and 33 females with an age range of 18 - 70 with a median of 31.5 years. Two 4 color panels of monoclonal antibodies were used: Abstract 2 CD38FITC/CD123PE/CD34ECD/CD45PE-PC5 and CD90FITC/CD133PE/ CD45ECD/CD33PE-PC5 analyzed on Navios Flow cytometer. Cell populations with different surface markers were calculated using the prism function of the software. Results were correlated to other prognostic parameters at diagnosis. The median value for each marker alone and in different combinations (panels) was used to divide the cohort into high and low expressers. Patients were treated by (3+7) protocol; they were followed up for a period of 0.2-18 with a median of 5.5 months and evaluated for overall survival and disease free survival. The study was performed according to Helsinki declaration for studies on human subjects and approved by the Institution Review Board (IRB) of the National Cancer Institute, Cairo University. An informed signed consent was obtained from all study subjects before enrollment. Results: Panels or MRD expression were not correlated to age, gender, hemoglobin level, Total leukocytic or platelet count.Among the studied single marker; A higher CD 123 % at diagnosis (<p=0.001) and at day (d) 14 (p=0.004 & p=<0.001 respectively) had an adverse impact on OS and DFS, but at d28 had no impact on either. A higher CD 133 % at diagnosis and at d14 (P=0.006 & P=<0.001 and P=<0.001 & P=<0.001 respectively), had an adverse impact on OS and DFS, but not at d28.
Among the panels; A higher [CD123+/ CD34-] % at diagnosis (P=0.040 & P=0.003) and follow up period (d14 & d28) (P=<0.001 & P=<0.001 and P=0.035 & P=0.002 respectively) had a significantly adverse impact on OS and DFS. A higher [CD34+/CD38-/CD123+] % at diagnosis (P=0.005 & P=<0.001) and follow up periods (at d14 and d28) (P=<0.001 & P=<0.001 and P=0.002 & 3 P=<0.001 respectively) was significantly associated with adverse impact on OS and DFS. A higher [CD34-/CD38+/CD123+] % at diagnosis (P=0.025 & P=<0.001) had adverse impact on OS and DFS, at d14 (P=0.029) had adverse impact only on DFS, but not at d28 at all.