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العنوان
Pattern of transaminases in relation to chemotherapy in patients with acute lymphoblastic leukemia as a predictor of hepatotoxicity
المؤلف
Mohamed Abd El-Aziz,Al-Shimaa
هيئة الاعداد
باحث / Al-Shimaa Mohamed Abd El-Aziz
مشرف / Manal Hamdy EL-Sayed
مشرف / Samar Mohamed Farid
مشرف / Shereen Mohamed Abd El-Ghany
الموضوع
 Acute Lymphoblastic Leukemia(ALL.
تاريخ النشر
2010.
عدد الصفحات
146.p؛
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
طب الأطفال ، الفترة المحيطة بالولادة وصحة الطفل
تاريخ الإجازة
1/1/2010
مكان الإجازة
جامعة عين شمس - كلية الطب - Pediatric
الفهرس
Only 14 pages are availabe for public view

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from 146

Abstract

This retrospective analytical study was conducted at Hematology/Oncology Clinic, Children’s Hospital, Ain Shams University during the period between February and August 2009. The study included 99 of cured ALL survivors that are relapse free for at least 12 months. Patients were divided according to risk group and protocol of chemotherapy received into 3 groups:
Group A: patients received BFM-90 protocol, standard risk group (BFM SRG) (49 patients) representing 49.50% of cases.
Group B: patients received CCG protocol, standard risk group (CCG SRG) (33 patients) representing 33.33% of cases.
Group C: patients received CCG protocol, high risk group (CCG HRG) (17 patients) representing 17.17% of cases.
There was no patient on BFM-90 protocol, high risk group.
Patients in group A were significantly older in age at the time of the study and had a longer duration of cure and longer duration of chemotherapy compared to the other 2 groups. There was no significant difference between the three groups regarding the age at diagnosis.
The number of patients who received combined chemotherapy and radiotherapy in group C (35.3%) were significantly higher compared to those in group A (8.2%) and B (3.0%).
The number of patients underwent serological screening for hepatitis markers were significantly higher in group B (60.6%) and C (58.8%) compared to group A (20.4%). In those who did the serological test markers, there were no HBsAg positive patients or HCV Ab positive patients in the three studied groups before initiation of chemotherapy.
All patients had received hepatitis B vaccination before initiation of treatment, as the obligatory hepatitis B vaccine was carried out since 1993. Booster doses of hepatitis B vaccination were given to some patients with ALL just after the diagnosis and before the initiation of treatment. Five patients in group A (10.2%), 17 patients in group B (51.5%) and 9 patients in group C (52.9%) received hepatitis B vaccine before the initiation of chemotherapy. Percent of patients that had received HBV vaccine was significantly lower in group A than the two other groups.
Fifty two patients underwent abdominal ultrasound before initiation of treatment of which, 20 patients in group A, 14 patients in group B and 4 patients in group C had abnormality in the form of hepatomegaly alone or hepatosplenomegaly with no statistically significant difference among the three groups.
There was no statistical difference among the 3 studied groups as regards the initial serum ALT, AST and ALT/AST ratio. Although total serum bilirubin level was significantly higher in group A, still within the normal range.
Some patients were vaccinated during phases of chemotherapy. Number of patients that were not vaccinated after completion of chemotherapy is significantly higher in group A (73.5%) than the 2 other groups.
Two patients in group A (4.1%) had positive HBsAg, while no one in group B or C were positive for HBsAg. As regards HBsAb, 22.4% of group A, 42.4 % of group B and 17.6 % of group C were positive. There were 15 patients in group A (30.6%), 2 patients in group B (6.1%) and 3 patients in group C (17.6%) tested positive for HCV Ab after completion of chemotherapy.
During follow up visits, no patients had jaundice, lower limb oedema, hepatomegaly or any other sign suggestive of chronic hepatic affection.
Regarding hepatitis B infection confirmed by PCR, patients in group A had more HBV infection (28.5%) compared to the other 2 groups. Patients that were HCV positive confirmed by PCR were significantly more in group A (34.7 %) compared to group B and group C (6.1% and 17.6 % respectively). No patient in the three studied groups developed hepatitis B and hepatitis C co-infection.
Hemoglobin levels were significantly higher in patients of group B compared to those of group A and C, meanwhile there was no statistical difference between the three studied groups regarding total leucocytic count, neutrophils or platelet count all through follow up period.
A significantly higher serum AST and ALT levels in group A and C compared to group B, while no significant difference among the 3 groups regarding ALT/AST, T.s.B, albumin and PT.
During period of chemotherapy, liver transaminases levels were followed up. In each phase of chemotherapy 3 readings of ALT, AST and ALT/AST were recorded; at onset, mid-phase and at end. The mean of the three readings was calculated. ALT level was significantly higher in group A compared to group B (during phases 3, 8, 9, 10, 11 and 12) and group C (during phase 8,9,11 and 12).
AST level was significantly higher in group A compared to groups B (during phases 3, 8, 9, 10 and 11) and group C (during phases 8,9 and 12).
There was no statistically significant difference among the three studied groups as regards the total number of hepatitis flares, number of modified doses and number of DROPped doses during the period of chemotherapy.
Elevated liver enzymes (ALT and/or AST) were the commonest cause of dose modification of chemotherapy in group A, while neutropenia was the commonest cause of modification in the other 2 groups. Severe infection and gastroenteritis were infrequently cause modification of doses of chemotherapy, with equal distribution in the 3 groups.
Chemotherapy was interrupted, either due to elevated liver enzymes (ALT and or AST) > 5 folds, or due to neutropenia or other causes such as herpetic eruption, fever, infection (chest, throat, otitis media) or patient’s non compliance (absent). There was no significant difference between the 3 groups of patients regarding the cause of DROPped doses. Except in cycle 3 where Patients in group A show significantly higher number of DROPped dose due to elevated liver function and neutropenia compared to the other 2 groups.
There was significantly positive correlation between ALT and AST at the end of chemotherapy and the number of hepatitis flares, number of modified doses and number of DROPped doses in group A. There was significantly positive correlation between ALT and AST at the end of chemotherapy and number of hepatitis flares in group B and C.
Patients who were positive for hepatitis B and C viruses had significantly higher number of modified doses, mean level of ALT and AST both at the end of chemotherapy and during follow up period compared to those who were negative. Also positive patients had higher number of DROPped doses, higher levels of total serum bilirubin and lower albumin levels during follow up although the difference was not statistically significant.
Patients, who had hepatomegaly or hepatosplenomegaly by US at presentation showed more hepatitis flares, modified doses, DROPped doses than those who had normal US at presentation. Also those who had hepatomegaly or hepatosplenomegaly had higher levels of ALT, AST both at the end of chemotherapy and during follow up, higher levels of total serum bilirubin and lower levels of albumin although all these differences were not statistically significant.