Prevalence of Gene Rearrangement by Multiplex PCR in De Novo Acute Myeloid Leukemia in Adult Iraqi Patients

BACKGROUND: Acute myeloid leukemia (AML) is a complex, heterogeneous disease driven by acquired somatic mutations. The presence of specific mutations advances stratification, treatment, and prognosis. Linear accumulation of mutations over time is a crucial factor in cancer development, particularly among elderly patients. Our recent study on gene rearrangement in AML revealed a significant association between age and adverse risk cases. AIM: The aim of this study was to examine the distribution of age, molecular characteristics, risk stratification, and treatment response based on age among patients with de novo AML in Iraq. PATIENTS AND METHODS: A prospective cohort study enrolled 115 Iraqi adult patients diagnosed with de novo AML using morphology and flow cytometry from December 2020 to May 2022. The Leukemia Q-Fusion Screening Kit, employing multiplex reverse transcription–real-time quantitative polymerase chain reaction with 30 gene rearrangements, was employed for the identification of gene rearrangement. The patients received care and follow-up at the Hematology Unit of Baghdad Teaching Hospital in Medical City. Ethical approval from the College of Medicine’s Ethical Committee at the University of Baghdad was secured before commencing the research, ensuring adherence to ethical standards throughdout the study. RESULTS: The age distribution exhibited a bimodal pattern, with a mean of 45.1 ± 17.5 years, ranging from 18 to 84 years, and a median of 46 years. A total of 39.1% of patients were diagnosed with AML before the age of 35 years, while 43% were diagnosed after the age of 51 years. AML patients with RARA mutations, RUNX1:: RUNX1T1 alterations, and NPM1 mutations were predominantly observed in younger individuals, as well as those diagnosed with AML defined by differentiation. Conversely, KMT2A rearrangements were more prevalent among older age groups, with a statistically significant difference in the distribution of AML classifications according to the World Health Organization (WHO) by age categories (P = 0.001). The risk stratification based on age and response assessment showed a notable higher risk profile observed among elderly patients that was associated with adverse risk and poorer response and mortality (P < 0.05). The prediction of treatment response accuracy rate was improved by adding age to the WHO classification and ELN 2022 risk stratification (73.5%–87.9%). CONCLUSION: Age significantly influences AML prognosis and treatment response. Incorporating age into risk stratification improves accuracy. Tailored approaches considering age are vital for optimizing AML management and outcomes.

Age-related dynamics in acute myeloid leukemia: Implications for prognosis, risk stratification, and treatment response

Aljabban,

Alalsaidissa

2024

Lysine (K)-specific methyltransferase 2A (KMT2A) rearrangements among Iraqi de novo acute myeloid leukemia

Al Jadir,

Abdulameer,

Alalsaidissa

et al. 2024

BACKGROUND: The classification of acute myeloid leukemia (AML) has evolved extensively over the last 20 years significantly, impacting the diagnosis and prognosis of the patients. The lysine (K)-specific methyltransferase 2A (KMT2A) gene, which has more than 80 gene fusions, is present in approximately 10% of all leukemias. Most KMT2A rearrangements are associated with adverse prognosis and need heavy chemotherapy protocol upfront. OBJECTIVE: This study aims to study the prevalence of KMT2A gene fusion among Iraqi patients with AML and its association with clinical and hematological parameters and patients’ outcomes. PATIENTS, MATERIALS, AND METHODS: A prospective cohort study conducted between December 2020 and May 2022 enrolled 115 Iraqi adults newly diagnosed with AML at the Hematology Unit of Baghdad Teaching Hospital. The patients were also monitored at this facility during the study period. Genetic rearrangements were detected using the Leukemia Q-Fusion Screening Kit through Real-Time Quantitative Reverse Transcription PCR (RT-qPCR) analysis. RESULTS: KMT2A rearrangements were identified in 23 (20%) patients. The most common was t(10;11) which presented in 15 (13%) patients, followed by t(9;11) in 5 (4.3%) patients and t(11;17) in 3 (2.6%) patients. Patients with KMT2A rearrangements were significantly older and more likely to have splenomegaly. At 1-month posttreatment, they had significantly lower red blood cell counts and hemoglobin levels and higher blast percentages. Only 4.3% achieved complete remission (CR) compared to 76.1% without KMT2A rearrangements, with a significantly higher mortality rate (30.4% vs. 5.4%, P = 0.0001). Regarding the treatment response, no significant differences were observed among the different fusion types of KMT2A rearrangements. CONCLUSION: KMT2A rearrangements are more prevalent among Iraqi AML patients compared to the global trend and are associated with older age, higher rates of splenomegaly, poorer hematological recovery, and worse outcomes, regardless of the KMT2A rearrangement fusion type.

Incidence of QT interval prolongation during arsenic trioxide-based therapy in a sample of Iraqi adult patients with acute promyelocytic leukemia (a single-center experience)

Hassan,

Almothaffar

2024

BACKGROUND: Arsenic trioxide (ATO) regimen is now the standard of care for acute promyelocytic leukemia (APL). The complete remission and possible cure are reported to be 50%–80% of APL patients. Prolongation of the QT interval has been consistently observed in clinical trials with ATO, which is known to have a direct effect on cardiac repolarization with the recommendations for management include electrocardiogram (ECG) monitoring, discontinuation of drugs that prolong the QT interval, and careful repletion of serum potassium and magnesium. OBJECTIVES: To study the incidence and clinical consequences of QT prolongation in a sample of Iraqi APL patients treated with ATO. PATIENTS AND METHODS: A prospective, cross-sectional study was conducted on 24 adult patients with newly diagnosed APL at Baghdad Teaching Hospital. ECG was performed at baseline and twice weekly till the end of induction treatment course. Corrected QT interval was calculated based on Bazett and Fridericia formulas (QTc interval of more than 500 ms is considered dangerous): Serum potassium, calcium, and magnesium levels were also measured simultaneously. RESULTS: The mean QT at baseline was 424 ± 18 ms and 402 ± 15 ms by Bazett and Fridericia, respectively, and at the end of induction, the mean QT was 436 ± 20 ms and 418 ± 20 ms by Bazett and Fridericia, respectively. The rate of developing prolonged QT was 62.5% by Bazet, in which 15 patients developed prolonged QT (at any time point). The comparison between prolonged and dangerous QT groups by Bazet showed significant difference, in which QT-related complications were associated with dangerous QT (>500 ms) prolongation significantly, while Fridrica method did not label these patients as having dangerous QT prolongation. The change in QT started as early as 1 week after treatment, the comparison between baseline QT and QT at week 1 showed that there was significant increase in QT. The electrolytes analysis and comparison with baseline results for potassium, magnesium, and calcium showed that there were no significant differences over time for tested electrolytes. CONCLUSION: Bazett formula is useful to monitor Iraqi patients with APL who are treated with ATO for the detection of dangerous prolongation of QT.