The Relationship between FLT-3 mutation and the response to treatment in children with acute myelocytic leukemia

Abstract

Background: Acute  Myelocytic Leukemia (AML)  is a rare disease with annual diagnosis of new cases about  (500-600) case/year  in USA, and (30-45) cases according to the statistics of the unversity children hospital in Damascus . The surviving rates in the patients of AML are  still modest in the last three decades and doen’t exceed of (30-40%).

The modification in the systems of the diagnosis and the chemotherapy and the supportive care have improved the prognosis of the patients who  have acute myelocytic  leukemia in the last years significantly .

However , a high rate of children don’t respond to the first line treatment or they relapse , and they need to undergoing a new treatments . So the need  was highlighted to discover  new agents  other than chemotherapy in the last years to overcome drug-related  complications of resistance and toxicity . among these agents is the identification of  the molecular mutations and the cytogenetic abnormalities and their diagnostic and therapeutic relevance to acute myelocytic leukemia  warning .

FLT-3  is tumor gene of the receptors for tyrosine kinas class 3 . who interfers with the basic stages of the hematopoiesis. Such as reproduction, differentiation and survival . in the recent years , the  FLT-3 mutations  become important marker in the hematological malignancy , and they have a prominent  and distinguished role in the acute myelocytic leukemia as these mutations have been associated with clinical prognosis , treatment , and survival in children .

We will analyze the occurrence of these mutations in patients with acute myelocytic leukemia with its differnt subtypes .and determine  their prevalence rate in the AML  patients , and will study their prognostic value and their relationship to response to treatment .

Methods : the study we are doing is a prospective , longitudinal, interventional , diagnostic , cohort study .

The study includes a sample size consisting of (49)patients who have been diagnosed withe acute myelocytic leukemia who were referred to the university children’s hospital and BASMA Association Support children with Cancer in 2019, and have a normal karyotype The patients were followed up by conducting an analysis PCR to identify   the FLT-3 Mutations and then studying the prevalence of these mutations and the relationship of their presence to response  to treatment .                                                         

Results :the study showed that there is no real statistically significant correlation between the presence of mutations and the response to treatment at the end of the INDUCTION stage  according to the resulting probability value (P –VALUE= 0.380)

Conclusions : It is necessary to evaluate FLT-3 mutations in patients  with acute myelocytic leukemia befor starting treatment . and conduct other studies in order to evaluate the relationship of the presence of  FLT-3 mutations with the rate of survival (os) and the event –free  rate (EFS) in AML  Patients , because that might enable us to formulate a better treatment plan and know the prognostic aspects in each case .