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All Trans Retinoic Acid (ATRA) therapy in acute promyelocytic leukemia AML-M3 Results of treatment of 29 Iraqi adult patients with AML-M3
نتائج العلاج لـ(29) مريض عراقي بالغ بمرض ابيضاض الدم النقياني الحاد نوع M3 بعقار اترا

Author: Ibrahim Khalil Al-Shemari ابراهيم خليل الشمري
Journal: IRAQI JOURNALOF COMMUNITY MEDICINE المجلة العراقية لطب المجتمع ISSN: 16845382 Year: 2012 Volume: 25 Issue: 2 Pages: 119-123
Publisher: Al-Mustansyriah University الجامعة المستنصرية

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Abstract

Background: All trans Retinoic acid (ATRA) when combined with chemotherapy induce complete remission in more than 85% of cases of AML-M3 , and significantly increase overall survival (OS) and Leukemia Free Survival (LFS). Aim of the study: to evaluate the efficacy of ATRA therapy in low dose (25mg/m2) together with anthracyclin-based regimen in achieving (Complete Remission) CR in patients with AML-M3.Patients and methods: Twenty nine patients with newly diagnosed AML-M3 (acute promyelocytic leukemia) based on morphology according to FAB (French-American-British) association enrolled between December2003 to June 2006. For induction of remission with ATRA therapy in dose of 25 mg/m2/day in two divided doses for 4-6 weeks along with anthracyclin-based chemotherapy and closely monitored clinically and laboratory to evaluate the response and to look for the complications . Mean follow up duration was 108 weeks.Results: Twenty nine patients with mean age of 43 year. Twenty three patients were cases of classical AML-M3 (79%) and 6 were cases of variant subtype (21%). Sixteen patients (55%) were males while 13 (45%) patients were females, Twenty one patients (73%) achieved complete remission, with induction related mortality of 27% (8 patients of 29). Three died because of ATRA syndrome, three due to sepsis and the other two because of intracranial hemorrhage, Three patients of those who achieved complete remission (CR) eventually relapsed, two within the first year of CR and died because of their disease, while the third one relapsed after one year of CR and achieved a second remission, After a median follow of 108 weeks the DFS was 86% and the OS 66%. Nine patients developed ATRA syndrome which proved to be fatal in three of them.Conclusion: ATRA therapy in a dose of 25 mg/m2/day in two divided doses with anthracyclin-based chemotherapy achieved CR in the majority of newly diagnosed adult Iraqi patients with AML-M3.Key words: AML-M3, ATRA

الخلفية:لقد اثبت الدراسات الحديثة بان استخدام عقار اترا مع العلاج الكيمياوي لعلاج هذا النوع من ابيضاض الدم النقياني الحاد يزيد نسبة الهوادة الكلية للمرض بـ85% كذلك نسبة البقاء على قيد الحياة الكلية ونسبة البقاء على قيد الحياة بدون اثر للمرض, لكن لهذا العلاج بالرغم من هذه الفوائد اعراض جانبية خطرة ولهذا يجب مراقبة المريض بصورة دقيقة خلال فترة استخدام العلاج للكشف عن هذه المضاعفات ومعالجتها سريعاً.الهدف من الدراسة:الغرض من هذه الدراسة هو لتقييم استخدام عقار اترا بجرعة اقل مع العلاج الكيمياوي في معالجة هذا النوع من ابيضاض الدم النقياني الحاد لدى المرضى البالغين في العراق.الطريقة:تم استخدام هذا العلاج لتسعة وعشرون مريضاً في ردهة أمراض الدم / مستشفى بغداد التعليمي للفترة من كانون الأول 2003 إلى حزيران 2006 وبجرعة ( 25 ملغم / م2) مرتين يومياً لمدة 6-8 أسابيع مع العلاج الكيمياوي، تم متابعة المرضى لتحديد الاستجابة او للكشف عن المضاعفات سريرياً ومختبرياً لمدة 108 أسبوع.النتائج:ان نسبة الهوادة الكاملة 73% ونسبة البقاء على قيد الحياة الكلية 66% ونسبة البقاء على قيد الحياة بدون اثر للمرض 86%.أظهرت الدراسة إن نسبة الوفاة عند استخدام العلاج في المرحلة الأولى 27% واوعز هذا إلى متلازمة اترا او الخمج او بسبب نزف دماغي، أصيب 9 من المرضى بمتلازمة اترا وتوفي ثلاثة منهم.الاستنتاجات:ان استخدام عقار اترا بجرعة (25 ملغم / م2) مرتان يومياً مع العلاج الكيمياوي المعتمد على الانثر اسايكلين اثبت فائدة في تحقيق نسبة هوادة كلية جيدة للمرضى البالغين في العراق المصابين بمرض ابيضاض الدم النيقاني الحاد M3.لهذا العقار مجموعة من الاعراض الجانبية الخطرة والتي تحتاج الى المراقبة الدقيقة والعلاج المبكر.

Keywords

AML-M3 --- ATRA


Article
THE FREQUENCY OF FLT3 MUTATION IN FIFTY FIVE IRAQI ADULT PATIENTS WITH ACUTE MYELOID LEUKEMIA

Authors: Maysaa AR Dhahi ميساء عبد الرزاق ضاحي --- Subh S. Al-Mudallel صبح سالم المدلل --- Ethar K Dhahir ايثار كاظم ظاهر
Journal: IRAQI JOURNAL OF MEDICAL SCIENCES المجلة العراقية للعلوم الطبية ISSN: P16816579,E22244719 Year: 2012 Volume: 10 Issue: 2 Pages: 140 -147
Publisher: Al-Nahrain University جامعة النهرين

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Abstract

Background: Mutations within the FLT3 gene, which code for the class-III-receptor kinase FLT3, ranked within the most frequent recurrent known genetic markers in acute myelocytic leukemia (AML). Internal tandem duplication (ITD) mutations in the juxtamembrane domain of FLT3 gene occur in 20-25% of AML.Objectives: This study designed to detect the frequency of FLT3-ITD mutation in adult AML patients, and to correlate the prevalence of this mutation with the clinical presentation of the patients and their response to induction therapy.Methods: The study comprised 55 AML patients and 33 healthy controls. For each patient, complete blood picture, blood film, bone marrow aspiration and biopsy was done. FLT3-ITD mutation was detected by conventional Polymerase Chain Reaction technology. Complete hematological remission achievement after induction chemotherapy was assessed by clinical examination and full laboratory investigations.Results: Out of 55 AML patients 8 (14.54%) had FLT3-ITD mutation and all of them presented as de novo AML. Moreover, 6 (75%) out of 8 mutated patients were newly diagnosed whereas 2 out of 8 were in relapse and were not on any therapy. The mean age of patients who had the mutation was lower than those without the mutation; also the majority of patients with mutation were male. The mean WBC count in mutated patients was not significantly higher than non-mutated patients. Higher bone marrow blast cell percent was found in mutated patients. FLT3-ITD mutation was mostly detected in M3 (37.5%) followed by M2 (25%), and lastly in M1 and M4 subtypes (12.5% for both subtypes) of FAB classification. Four out of 8 mutated patients failed to response to induction therapy although they were with good compliance to drug and 1/8 died throughout the induction therapy.Conclusion: Since FLT3-ITD mutation was associated with higher WBC count, significantly higher bone marrow blast cell percent and low rate of response to induction therapy; therefore it had been considered one of poor prognostic factor. It is a factor in defining risk stratification of AML patients.Keywords: AML, FLT3-ITD mutation, conventional PCR, FAB sub-types

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