الفهرس 
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Abstract
The efficacy and the toxicity of 6MP are mostly related with the
concentration of active TGNs, inter-patient differences in TPMTactivity
can have serious impact on the effects of this drug. There are more than
20 variant alleles of TPMT that cause decreased enzymatic activity. We
studied the most common variant alleles of TPMT and their frequency
distribution in the Egyptian children with acute lymphoblastic leukemia.
This study was conducted on twenty five patients with acute
lymphoblastic leukemia, their ages ranged from (1-18 years) with a mean
of age 6.4±4.0 years
All patients were submitted to detailed history taking and clinical
examination. Patient’s filing system was revised retrospectively for these
investigation at diagnosis.
- Complete blood count.
- Bone marrow examination at diagnosis, day 14 and day28 of
induction chemotherapy.
- Immunophenotyping and cytochemical analysis were
recorded if done.
- Identification of (TPMT) gene mutations by PCR technique
followed by RFLP analysis.
Results showed that:
1- In our study the mutant genotyping (20/25=80%) represented into:
TPMT*3A with alleles frequency of (16.12%) and genotyping frequency
of (56%), TPMT*3C with alleles frequency of (0.08%) and genotyping
frequency of(16%) , TPMT*3B with alleles frequency of (0.04%) and
genotyping frequency of (8%), all also represented into.
Summary
• Homozygous type that has mutant/mutant alleles(8/20=40%)
with genotype frequency of (32%),all of them represented in
(TPMT*3A /PMT*3A).
• Heterozygous type that has wild/mutant alleles
was(12/20=60%) with genotype frequancy of (48%)
represented in:
1-(Heterozygous TPMT*3A ) was the most prevelant
represented in( 6/20=30%) of mutant patients.
2- (Heterozygous TPMT*3C) represented in ( 4/20=20%) of
mutant patients.
3-( Heterozygous TPMT*3B ) represented in( 2/20=10%) of
mutant patients.
In (5/25=20%) of our patients, (N0*3A,*3B,*3C) was detected.
2-There was no statistical significant difference between
(no*3A,*3B*3C) and mutant patients as regarded complications of
chemotherapy during the course of treatment ,while the patients with
homozygous alleles needed significants prolonged duration of drug
interruption to the heterozygous alleles.
3- Although no significant difference between (no*3A,*3B*3C) and
mutant regarding duration of hepatotoxicity we can differentiate between
both at cut of point of( 3.5) weeks with sensitivity (100%)and
specificity(100%) ,regarding missed treatment in weeks we can
differentiate between (no*3A,*3B*3C) and mutant at cut of point
of(6.5)weeks with sensitivity (100%) and specificity(70%) .
4- Although no significant difference between homozygous and
heterozygous regarding duration of neutropenia we can differentiate
between both at cut of point of( (1.25) weeks with sensitivity (40%) and
Summary
specificity(100%), regarding duration of hepatoxicity we can differentiate
between both at cut of point of( (1.5) weeks with sensitivity (80%) and
specificity(60%), regarding missed treatment in weeks we can
differentiate between wild and mutant at cut of point of(5.5)weeks with
sensitivity (80%) and specificity(100%) .
5-Although there was no statistical significant difference between
(no*3A,*3B*3C) and mutant patients as regard overall survival, the
numbers of dead patients with mutant genotyping was more than of the
(no*3A,*3B*3C) type.
6- The numbers of dead patients with homozygous genotyping was more
than of the heterozygous with statistical significant regarding overall
survival comparison between homo and hetero genotype of TPMT.
7-Although there was no statistical significant difference between
(no*3A,*3B*3C) and mutant cases as regard relapse free survival, the
numbers of patients had relapse with mutant genotyping was more than of
the (no*3A,*3B*3C) type.
8-Although there was no statistical significant difference between
homozygous and heterozygous genotyping as regard relapse free
survival, the numbers of patients with homozygous genotyping had
relapse more than that of heterozygous genotyping .