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العنوان
Flow FISH CD 34+ CD38- analysis for detection of minimal residual disease in acute myeloid leukemia patients /
المؤلف
Abd Rabou, Ayman Ahmed Mahmoud.
هيئة الاعداد
باحث / أيمن أحمد محمود عبد ربه
مشرف / عصمت عبد العزيز الشرقاوي
مشرف / دعاء محمد سيد
مشرف / أيمن جميل غبريال
مشرف / مصطفي احمد السيد
الموضوع
Pathology, Clinical.
تاريخ النشر
2023.
عدد الصفحات
127 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
أمراض الدم
تاريخ الإجازة
12/3/2023
مكان الإجازة
جامعة المنيا - كلية الطب - الباثولوجيا الاكلينيكية
الفهرس
Only 14 pages are availabe for public view

from 128

from 128

Abstract

Following induction chemotherapy, whether one or two rounds, assessment of minimum residual disease (MRD) detects a tiny proportion of acute myeloid leukemia (AML) cells that may pose a significant clinical issue. It is possible to achieve MRD negative, which implies there are no identifiable leukemic cells, by employing a variety of techniques. One of these techniques included morphologically examining BM aspirated samples for blast cell percentages less than 5%. Another crucial technique was the immunophenotyping using flowcytometry for the identification of LICs (CD34+/CD38-). Cytogenetic finding by FISH technique consider one of the other methods in addition to RT PCR which is considered an important tool. Recently using NGS remains a promising method.
In this study we consider Flow-FISH analysis of CD34+/CD38- the leukemia initiating cells (LICs) after separation of these cells in AML patients who receive one cycle of induction chemotherapy for detection of MRD with the probability of relapse in positive cases and this will predict outcomes for patients with AML.
The results show when the blast cells were increased more than 5%, the LICs (CD34+/CD38-) would increase and the patients were positive for MRD with strong prediction for relapse and bad prognosis.
However comparing group II (blast cells > 5%) and were positive for CD34+/CD38- versus only 20 % positive cases with cytogenetic findings showed a strong correlation and P value was 0.0001. This meant that there were a strong correlation between cytogenetic findings by FISH and LICs CD34+/CD38- cases. Also a strong positive correlation was found when comparing group II (blast cells > 5%) and cytogenetic findings with 20 % positive cases. P value was 0.0001.
In group II, there had been a statistically significant association between CD34+/CD38- and the proportion of cytogenetic findings (P value = 0.007), and the correlation was quite high (rs = 0.784).
Since there is currently no consensus about the most effective approach for MRD detection, it is challenging to compare results in AML patients when employing several methods.
Despite these difficulties, it is believed that patients with high-risk AML should have frequent monitoring to ensure MRD negative (Cluzeau et al., 2022).
Limitations and challenges and recommendations in MRD assessment in AML
There are discrepancies in the methods employed in various research since MRD measures are not often utilized in AML. Sampling varies widely across studies; some detect MRD on peripheral blood samples, while others employ bone marrow samples (Jentzsch et al., 2019). Although studies have shown that bone marrow has higher MRD levels and greater sensitivity, collecting peripheral blood samples is more practical for the patient (Cluzeau et al., 2022).
For MFC MRD evaluations, the European Leukemia Networking group advises using first-pull bone marrow aspirates, however for molecular MRD assessments, either bone marrow or peripheral blood samples are acceptable (Heuser et al., 2021b).
The findings for people with high-risk illness are still debatable, despite new research suggesting that MRD evaluations might predict clinical outcomes in patients with favorable or moderate risk AML. Additional research is required to improve and harmonize the time and methods of MRD evaluation in AML patients, especially in those with high-risk illness (Cluzeau et al., 2022).
Regarding the time of MRD tests utilized in clinical trials, there is a great deal of variation. There is currently little agreement on when MRD measurements should be taken across different methodologies and goals. Measurements upon diagnosis, after two rounds of induction/consolidation chemotherapy, before HCT, and at the conclusion of treatment are advised by the European Leukemia Networking group (Heuser et al., 2021b).
However, depending on the therapeutic regimen, the patient group, and the MRD measurement type, the ideal duration may vary. For instance, MFC MRD evaluations conducted after the first induction were the most accurate predictors of clinical outcomes in patients treated with fludarabine, cytarabine, and idarubicin induction. Another research indicated that MFC MRD analysis at the conclusion of the first induction was the most effective predictor of outcomes in patients with high-risk AML who were receiving cytarabine, daunorubicin, and etoposide (Tsai et al., 2021). In a study of persons with AML who received conventional induction chemotherapy, NGS MRD evaluations done at the time of the initial consolidation were also predictive of the clinical outcomes at the 5-year mark (Tsai et al., 2021).