Cytogenetics in acute leukemia

Cytogenetic analyses in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) have revealed a great number of non-random chromosome abnormalities. In many instances, molecular studies of these abnormalities identified specific genes implicated in the process of leukemogenesis. The more common chromosome aberrations have been associated with specific laboratory and clinical characteristics, and are now being used as diagnostic and prognostic markers guiding the clinician in selecting the most effective therapies. Specific chromosome aberrations and their molecular counterparts have been included in the World Health Organization classification of hematologic malignancies, and together with morphology, immunophenotype and clinical features are used to define distinct disease entities. However, the prognostic importance of less frequent recurrent aberrations in AML and ALL, both primary and secondary, is still to be determined. This review summarizes current views on clinical relevance of major cytogenetic findings in adult AML and ALL.[1]

Comparison of Reduced-Intensity Hematopoietic Cell Transplantation with Chemotherapy in Patients Age 60-70 Years with Acute Myelogenous Leukemia in First Remission

We compared the outcomes of patients age 60-70 years with acute myelogenous leukemia receiving reduced-intensity allogeneic hematopoietic cell transplantation (HCT) in first remission (CR1) reported to the Center for International Blood and Marrow Research (n = 94) with the outcomes in patients treated with induction and postremission chemotherapy on Cancer and Leukemia Group B protocols (n = 96). All patients included had been in CR1 for at least 4 months. The HCT recipients were slightly younger than the chemotherapy patients (median age, 63 years vs 65 years; P < .001), but there were no significant between-group differences in the proportion with therapy-related leukemia or in different cytogenetic risk groups. Time from diagnosis to CR1 was longer for the HCT recipients (median, 44 days vs 38 days; P = .031). Allogeneic HCT was associated with significantly lower risk of relapse (32% vs 81% at 3 years; P < .001), higher nonrelapse mortality (36% vs 4% at 3 years; P < .001), and longer leukemia-free survival (32% vs 15% at 3 years; P = .001). Although overall survival was longer for HCT recipients, the difference was not statistically significant (37% vs 25% at 3 years; P = .08). Our findings suggest that reduced-intensity conditioning allogeneic HCT in patients age 60-70 with acute myelogenous leukemia in CR1 reduces relapse and improves leukemia-free survival. Strategies that reduce nonrelapse mortality may yield significant improvements in overall survival. [2]

Risk Factors for Acute Leukemia in Children: A Review

Although overall incidence is rare, leukemia is the most common type of childhood cancer. It accounts for 30% of all cancers diagnosed in children younger than 15 years. Within this population, acute lymphocytic leukemia (ALL) occurs approximately five times more frequently than acute myelogenous leukemia (AML) and accounts for approximately 78% of all childhood leukemia diagnoses. Epidemiologic studies of acute leukemias in children have examined possible risk factors, including genetic, infectious, and environmental, in an attempt to determine etiology. Only one environmental risk factor (ionizing radiation) has been significantly linked to ALL or AML. Most environmental risk factors have been found to be weakly and inconsistently associated with either form of acute childhood leukemia. Our review focuses on the demographics of childhood leukemia and the risk factors that have been associated with the development of childhood ALL or AML. The environmental risk factors discussed include ionizing radiation, non-ionizing radiation, hydrocarbons, pesticides, alcohol use, cigarette smoking, and illicit drug use. Knowledge of these particular risk factors can be used to support measures to reduce potentially harmful exposures and decrease the risk of disease. We also review genetic and infectious risk factors and other variables, including maternal reproductive history and birth characteristics. [3]

Level of Pentraxin-3 in Patients with Acute Leukemia in Septicemia and Its Prognostic Value

Introduction: In acute leukemia, sepsis is potentially fatal. Pentraxin3 is a protein rapidly produced in response to primary inflammatory signals. It shows high levels in sepsis, specially associated with vascular and end-organ damage.

Aim of the Work: To measure the level of PTX3 in sepsis in patients with acute leukemia and correlate its level to higher risk of complications compared with CRP.

Study Design: Prospective study.

Place and Duration of the Study: Department of hematology, Alexandria main university hospital, from April 2012 to August 2013.

Methods: The study included 60 patients, they had routine workup for leukemia. Serum CRP and plasma PTX3 levels were measured with ELISA on days 1, 2, 3 of febrile neutropenia after chemotherapy.

Results: Male to female ratio 1:1, age ranged from 18 to 62 years (median of 40 yrs). 41 patients suffered from acute myeloid leukemia, and 19 from acute lymphoblastic leukemia. High PTX3 levels on the 1st day of sepsis have been a strong indicator for development of complications (septic shock and mortality) (P=.001) compared to CRP (P=.032). High PTX3 level has been associated with coagulation impairment (P=.001). PTX3 showed sensitivity of 100% and specificity of 70% for prediction of bad prognosis, whereas CRP showed sensitivity of 88.5% and specificity of 60.5%.

Conclusion: PTX3 is highly recommended in diagnosis of sepsis in patients with acute leukemia during neutropenia and it shows high sensitivity and specificity in prediction of bad prognosis (septic shock, coagulation impairment and mortality) in comparison with CRP. [4]


Prognostic Implications of Expression of the Wilms Tumor 1 (WT1) Gene in Acute Leukemia (Experience from South Egypt)

Background: Wilms’ tumor (WT1) gene expression has been reported in the majority of acute leukemia patients at diagnosis and has been evaluated as a prognostic and minimal residual disease (MRD) marker but its role is still controversial.

Methods: Real-time quantitative polymerase chain reaction was used on bone marrow samples from 100 newly diagnosed adults and pediatrics acute leukemia patients (50 AML and 50 ALL patients). WT1 expression were examined at diagnosis and at the end of induction.

Results: WT1 was expressed in (14%) ALL and in (36%) AML patients. We found no statistically significant impact of WT1 expression at diagnosis on response p= 0.054, 0.057, DFS (P = 0.591, 0.858), or OS (p= 0.339, p= 0.331) in ALL and AML patients respectively. Persistence of WT1 expressions at the end of induction didn’t show any effect on relapse rate in AML however, it showed significant results in ALL p=0.045.

Conclusion: Our results suggest that WT1 expression in patients with acute leukemia doesn’t have any implication on response or survival however, significant association was found in predicting ALL relapse but the small sample size should be considered.[5]

Reference

[1] Mrozek, K., Heerema, N.A. and Bloomfield, C.D., 2004. Cytogenetics in acute leukemia. Blood reviews, 18(2), pp.115-136.

[2] Farag, S.S., Maharry, K., Zhang, M.J., Pérez, W.S., George, S.L., Mrózek, K., DiPersio, J., Bunjes, D.W., Marcucci, G., Baer, M.R. and Cairo, M., 2011. Comparison of reduced-intensity hematopoietic cell transplantation with chemotherapy in patients age 60-70 years with acute myelogenous leukemia in first remission. Biology of Blood and Marrow Transplantation, 17(12), pp.1796-1803.

[3] Belson, M., Kingsley, B. and Holmes, A., 2007. Risk factors for acute leukemia in children: a review. Environmental health perspectives, 115(1), pp.138-145.

[4] Elghandour, A., Naenaa, H., Eldefrawy, M., Elbordeny, M. and Mohammed, H. (2015) “Level of Pentraxin-3 in Patients with Acute Leukemia in Septicemia and Its Prognostic Value”, International Blood Research & Reviews, 4(1), pp. 1-7. doi: 10.9734/IBRR/2015/17737.

[5] Ibrahim, A., Badrawy, H. and Sayed, H. (2015) “Prognostic Implications of Expression of the Wilms Tumor 1 (WT1) Gene in Acute Leukemia (Experience from South Egypt)”, Journal of Advances in Medicine and Medical Research, 7(1), pp. 61-71. doi: 10.9734/BJMMR/2015/15834.

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