| Abstract: |
The aim of this work is to evaluate plasma level of VEGF in CML patients in different phases (chronic ,accelerated and blastic).And to correlate it with well known prognostic factors in order to establish its prognostic significance.The study was conducted on thirty five individuals classified into two groups :Patient group : Twenty five newly diagnosed chronic myeloid leukemia patients, 16 males (64%) and 9 females (36%). With their age ranged from 27 to 75 years with a mean ± SD 55.1 ± 12.9 years.They were subdivided into : -a) chronic phase subgroup (n = 15) their diagnosis based on* Full blood count with stained blood film (Marked Leucocytosis with presence of all granulocytic components –Basophilia )* Cytochemistry : Neutrophil Alkaline Phosphatase (NAP Score) which is low or absent.B ) Accelerated Phase subgroup (n = 5 ) their diagnosis based on :- Peripheral blast count < 5%.- Peripheral basophile count <10%.- Bone marrow blast count <10%.- Platelet count < 100 x 103.c) Blastic phase subgroup (n = 5) their diagnosis based on :- peripheral blast count > 30 %- Bone marrow blast count < 30%- Immunophenotyping ( 4 cases diagnosed in Myeloid blastic crisis CD13,CD33 positive and 1 case diagnosed in Lymphatic blastic crisis CD 19,CD20 Positive ).N.B : patients diagnosed in Accelerated and blastic phases already receiving chemotherapy for chronic phase CML ( 5 receiving hydroxy urea , 3 receiving combined therapy hydroxy urea and interferon ? and 2 receiving busulfan ). but they did not receive any management protocols for the new event (developing into accelerated or blastic phases) before sampling.Control group : Ten apparently healthy control subjects 7 males (70%) and 3 females (30%) they are age and sex matching with patient group. Their age ranged from 27 to 75 years with a mean ± SD 49 ± 14.7 .. All of them had no history suggesting any clinical, metabolic and haematological disorders. Routine Investigations (C.B.C , liver , kidney functions ) confirm their healthy state.For the patient group the following was done :1- Full history taking laying stress on age together with famous symptoms of CML including fatigue ,weight loss, easy brusing and bleeding.2- Thorough clinical examination laying stress on Splenic Size.3-Full blood count and stained blood films with Leishman stain .Laying stress on:- morphological characters of chronic myeloid leukemia (Marked Leucocytosis with presence of all granulocytic components –Basophilia )- Total leucocytic count (T.L.C.)- Number of Peripheral Blasts- Haemoglobin Concentration (Hb)- Platelet Count- Number of Peripheral Basophiles4-Cytochemical examination by Neutrophil Alkaline Phosphatase (NAP Score).5 – Routine liver and kidney functions.6- Measurement of plasma level of VEGF using ELISA technique.For cases with increased peripheral blasts > 5% the following was added:- Bone Marrow Examination with leishman stained film to confirm diagnosis of cases in accelerated and blastic crisis.For cases in blastic crisis ( peripheral blasts > 30%)the following was added:- Peroxidase stained freshly prepared blood film to differentiate myeloid from lymphoid blastic crisis.-Immunophenotyping to classify type of this blastic crisis.For control group the following was done :-Routine Investigations : encloding C.B.C , Liver, Kidney functions-Specific Investigations : Measurement of plasma level of VEGF using ELISA technique.The results of the study showed that plasma VEGF increased in all cases of CML in different phases when compared with control group. As regard difference in VEGF concentration between different phases of CML. Least significant difference (LSD) between each two phases and controls was done with the following results :There was statistically significant difference in VEGF conc. between :- Each of the three phases of CML and controls (p < 0.01).There was No significant difference in VEGF conc. between :-- each of the three phases of the disease ( p > 0.05).Correlation study of VEGF together with well established prognostic markers of CML revealed the following :-Plasma VEGF levels positively correlated with total leucocytic count, number of peripheral blasts , number of peripheral basophiles, splenic size.Negatively correlated with haemoglobin concentration.Not correlated with platelet count and age of the patientConclusionIn our study , we confirm the increase of VEGF plasma levels in newly diagnosed CML cases. Also we observe significant correlations between plasma VEGF concentration and well established prognostic markers in CML such as number of peripheral blasts , splenic size , haemoglobin concentration , total leucocytic count , number of Peripheral basophiles Supporting the hypothesis that VEGF may have a prognostic role in CML and targeting VEGF might be a potential therapeutic strategy in chronic myeloid leukemia .RecommendationsIt is advisable to do further prospective studies with larger number of patients and follow up of them during the course of the disease aiming to correlate the plasma VEGF level with patient survival in univariate and multivariate regression analysis in order to ensure its prognostic significance
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