Introduction
As rates for curing childhood acute lymphoblastic leukemia (ALL) increased, study of adverse effects of chemotherapy became an important. Osteonecrosis is one of these complications.
It affects up to 33% of patients treated for ALL.
Osteonecrosis may result in severe pain in joint, limitations on physical activity, some cases need to surgical intervention to restore function.
Corticosteroids administration is one of important hazards for osteonecrosis as it has been reported to induce ischemia, upregulate apoptosis of osteoblasts and osteocytes, and prolong osteoclast lifespans.
Different gene studies have reported several polymorphisms in genes related to the development of osteonecrosis, such as plasminogen activator inhibitor-1 (PAI-1) , vitamin D-receptor(VDR)
Polymorphism in the plasminogen activator inhibitor-1 (PAI-1) gene and vitamin D-receptor genetic(VDR) variants have been connected with bone and vasculature morbidity, these pharmacogenetic associations likely mirror to the interaction of antileukemic medications with germline sensitivity to drug actions, and might distinguish ALL patients at highest risk to develop osteonecrosis.
However ,there is studies debated about association of Plasminogen activator inhibitor-1 gene and osteonecrosis in acute lymphoblastic leukemia.
Rational
Osteonecrosis is a severe complication of therapy in children with acute lymphoblastic leukemia. Polymorphisms in Plasminogen activator inhibitor-1 gene and vitamin D- receptor gene may be related to osteonecrosis.
RESEARCH QUESTION
-What is the frequency of osteonecrosis in children with acute lymphoblastic leukemia?
-Is there a role of polymorphisms in Plasminogen activator inhibitor-1 gene and vitamin D- receptor gene in development of osteonecrosis ?
AIM OF THE WORK
To define important risk factors for osteonecrosis in childhood acute lymphoblastic leukemia.
OBJECTIVES
1- To determine polymorphisms of Plasminogen activator inhibitor-1 gene and vitamin D- receptor gene in children with acute lymphoblastic leukemia.
2- To determine the association between polymorphisms of Plasminogen activator inhibitor-1 gene and vitamin D- receptor gene and development of osteonecrosis as acomplication of treatment.
Subjects & Methods
1-Technical design:
A) Site of study: This work will be carried out on pediatric patients in heamatology and oncology unit , children's hospital,zagazig university.
B) Type of study: Comprehensive study.
C)Sample size: All acute lymphoblastic leukemia patients admitting to heamatology and oncology unit , children's hospital,zagazig university.
d)subjects included in the study:
Inclusion criteria:
1-Newly diagnosed hospitalized children with acute lymphoblastic leukemia,(both sexes,age:1-18years )
Exclusion criteria:
1.Hospitalized patiants who newly diagnosed with acute lymphoblastic leukemia and previously diagnosed by osteonecrosis.
2. Patiants with other malignancies.
3. Patients who on chemotherapy.
4. Relapse acute lymphoblastic leukemia.
2)Operational design:
-Steps of performance and techniques:
All patients will be subjected to followings:
-Full medical history.
-Full clinical examination:(General & local).
-The following investigations:
1-CBC,serum electrolytes, serum calcium, phosphate, vitamin D and alkaline phosphatase.
2-Bone marrow examination.
3-Blood sampling: 2 ml whole blood for detection of polymorphisms in Plasminogen activator inhibitor-1 gene and vitamin D- receptor gene by PCR(polymerase chain reaction).at start of treatment.
-Imaging:
1-Magnetic resonance imaging (MRI) on hip.
2-Xray on hip.
3) Administrative design:
-Consent will be obtained from relatives of patients.
-Approval for performing the study will be obtained from pediatric Department, Faculty of Medicine, Zagazig University after Institutional Review Board of Zgazig University (IRB-ZU) approval.
Results
The collected data will be presented in tables and suitable graphs and analyzed by )SPSS) Statistical Package for the Social Sciences program using appropriate statistical methods .
DISCUSSION
Discussion will be done on results compared to related relevant literatures and scientific researches. To explain the reasons for getting such results .
CONCLUSION and RECOMMENDATIONS
It will be derived from the findings of the study.