Childhood Acute Leukemia Patients Research Articles

Impact of TP53 gene variants on prognosis and survival of childhood acute lymphoblastic leukemia

The tumor suppressor protein 53 (TP53) gene is one of the most studied genes in cancer. Although TP53 variants are rare events in acute leukemia, recent observations showed that relapse samples might harbor TP53 variants. Here, we aimed to determine TP53 variants (hotspot region, exon 4–11) in childhood acute lymphoblastic leukemia (B and T-ALL) patients (n = 94) including diagnostic-relapse pairs (n = 15) by amplicon sequencing and evaluate the clinical impact of these variants. In total, nine different (E298*, R283C, R273H, L252F, C229F, I195T, E286G, c.955_956insC, and c.920-1G > C) variants were identified in 17 (18%) childhood ALL patients. c.(920-1G> C) splice site variant and c.(955_956insC) insertion were reported for the first time. In diagnose-relapse pair samples, we identified acquired and/or loss of TP53 variants in the samples at the time of relapse. TP53 variants were found to be more common in T-ALL (37%) than in B-ALL patients (9%). Pathogenic TP53 variants were associated with a shorter overall survival time (p = 0.001).TP53 variants were found to be associated with inferior outcomes in our cohort and can be an independent risk factor for poor prognosis in childhood acute leukemia patients. Identification of low-frequent variants with next-generation sequencing approaches enables better knowledge of the clonal dynamics of ALL.

Molecular Cytogenetics and Immunophenotypic Characterization of Childhood Acute Leukaemia Patients in Tertiary Care Center of Bangladesh – An observative study

Background: Childhood leukemia is genetically a heterogeneous disease. Various types of cytogenetic abnormalities and immunophenotypic character are present in leukaemia which are important for risk stratification, treatment and play as significant prognostic factor. Pediatric acute leukaemia presents with varying clinical, morphological, immunological and molecular characteristics. It is very highly curable if diagnosed and treated properly. For detail typing and subtyping of acute leukemia immunophenotyping and cytogenetics are crucial. The aim of this study was to find out the genetic abnormalities and immunophenotypic characterization of childhood acute leukaemia patients in Bangladesh. Material & Methods: This was a retrospective observational study and was conducted in the Department of pediatric hemato-oncology of Combined Military Hospital, Dhaka and Ahsania Mission Cancer Hospital, Mirpur, Dhaka, Bangladesh during the period from February,2014 to March, 2022. There was total 98 cases of acute leukaemia. Results: In total 98 patients completed the study. We found that 79.59% patients were ALL and 20.41% patients were AML. Among ALL 80.64% were B cell type, 6.40% were T cell Type ; 12.82 % had TEL/AML1 or ETV6/RUNX1 t(12;21)(p13;q22), 5.13% patient had TCF3/PBX1 or E2A/PBX1 t(1;19)(q23;p13). In AML30.00% patient had PML/RARAt(15;17)(q22;q21), 10.00% patient had AML1/ETO or RUNX1/CBFA2T1 t(8;21) (q22;q22), 5.00% patient had FLT3/ ITD. In case of B-ALL highest expression of antigen was CD19 (91.64%) followed by CD10 (80.58%), HLADR (67.94%), CD22 (72.68%), CD79a (72.68%), TdT (52.14%) and CD34 (48.98%). In 44.24% cases there was co-expression of CD10 and CD19 and there was 11.6% expression of myeloid marker CD13 and 1.58% expression of T cell marker CD5. In case of T-ALL there was 100% expression of CD3. Expression of other antigen CD4, CD5, CD7, CD8, CD4/8 co-expression, TdT was 60%. There was 40% expression of CD1a and CD2. There was 20% expression of CD10, CD34 and TCRab also. In case of AML highest expression was MPO (93.75%) followed by CD33 (87.50%), CD13 (81.25%), CD117 (75%), HLADR (43.75%) and CD64 (50%). There was 6.25% aberrant expression of B-ALL marker CD19 and T-ALL marker CD3, CD4, CD5, CD7 also. Conclusion: Depending on this study we can say that except few variations distribution of immunophenotypical subtypes and genetic abnormalities of childhood acute leukaemia are almost similar to other literature published from neighboring countries.This study will serve as a guideline for future study in our country in this aspect.

Clinical, laboratory features and some genetic abnormalities in childhood acute leukemia at Hue Central Hospital, Viet Nam

Background: Acute leukemia is the most common malignant disease in children. Some genetic abnormalities have been recognized to have prognostic or therapeutic relevance. Objective: To analyze the clinical presentations, laboratory features, and genetic abnormalities in childhood acute leukemia patients. Materials and methods: It was a descriptive cross-sectional study on childhood acute leukemia patients who admitted to the hospital between November, 2017 and May-2022. Results: There were 83 new patients with acute lymphoblastic leukemia (ALL) (70.3%) and 35 patients with acute myeloid leukemia (AML) (29.7%), the ratio of male to female was 1.51:1. The median age was 5.8 ± 4.0 years. The most common symptoms were anemia (87.3%), hepatomegaly (48.3%), enlarged lymph nodes (44.9%), fever (44.9%), splenomegaly (41.5%), bleeding (39.8%) and bone pain (21.2%). Regarding laboratory features, white blood cell (WBC) median is 12.3x109/l, there is 28.8% of the patients with WBC ≥ 50x109/l. Platelet (PLT) median is 43,5x109/l, there is 75.4% patients with PLT <100x109/l. Hemoglobin (Hb) mean is 8.0 ± 2.3 g/dl, there is 78.9% patients with Hb < 10 g/dl. In ALL, genetic analysis showed that 18.1% patients have NUDT15 polymorphism, 6.9% patients have TPMT polymorphism, 12.1% patients have TEL/AML1, 4.8% patients with BCR/ABL1, 2.4% patients with MLL/AF4, 3.6% patients with E2A/PBX1 and 1.2% patient with SET/NUP214. In AML, the percentage of AML1/ETO, AML1/ETO+BCR/ABL1, PML/RARA, MLL/AF6 and KMT2A/MLLT10 were 14.2%, 2,9%, 8.6%, 5.7% and 2.9% respectively. Conclusions: The most common clinical presentations were anemia, hepatosplenomegaly, fever, enlarged lymph nodes, bleeding and bone pain. Some genetic abnormalities help classification, prognosis and treatment for childhood acute leukemia. Key words: Acute leukemia, children, genetic abnormalities.

Investigation of Port Catheter-Associated Infections in Childhood Acute Leukemia Patients

Investigation of Port Catheter-Associated Infections in Childhood Acute Leukemia Patients

Incidence of venous thromboembolism in childhood acute leukemia patients - tertiary care centre experience from kingdom of Saudi Arabia

Incidence of venous thromboembolism in childhood acute leukemia patients - tertiary care centre experience from kingdom of Saudi Arabia

A case-control study on correlation of pesticide exposure with childhood acute leukemia

To evaluate the correlation of pesticide exposure with childhood acute leukemia. An exploratory case-control study was conducted among childhood acute leukemia patients under 15 years old in Shanghai, China. From January 1st, 2006 to December 31st, 2008, a total of 80 newly diagnosed acute leukemia patients were recruited from Shanghai Children's Medical Center for the case group. Another 96 age-matched patients who visited the hospital for health examination, pediatric treatment or osteological therapy excluding hematological system diseases and neoplastic disease, were recruited for the control group. A questionnaire survey was conducted in both groups; and a 30 - 40 ml random urine sample was collected from each participant. Five types of organophosphorus pesticide metabolites was then detected among the samples, using Gas Chromatography with Flame Spectrophotometry. According to result of the questionnaire survey, more participants (55.0% (44/80)) in case group than in the control group (33.3% (32/96)) reported using mosquitocidal, which might increase the risk of childhood acute leukemia (OR = 2.444; 95%CI: 1.326 - 4.506). At the same time, the detection showed that the concentration (median) of organophosphate metabolites diethyl phosphate, dimethyl phosphate, dimethyl thiophosphate, diethyl thiophosphate and diethyl dithiophosphate in case group were 0.0682, 0.0082, 0.0183, 0.0233, 0.4259 µg/g Cr, which were all significantly higher than in control group (0.0865, 0.0025, 0.0112, 0.0123, 0.1207 µg/g Cr) except the concentration of diethyl phosphate (Z = -1.081, P = 0.279). The difference showed statistical significance (Z = -5.752, -2.800, -3.316, -8.120, P < 0.05). Pesticide exposure may be one of the risk factors for childhood acute leukemia.

The Frequency of HLA Class I and II Alleles in Turkish Childhood Acute Leukaemia Patients

In this study, blood samples were taken from 200 patients with childhood acute leukaemias, including acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML), and from 100 healthy volunteers (controls). The frequency of the human leucocyte antigen (HLA)-DRB1*04 allele was significantly higher, and the frequencies of the HLA-A23 and HLA-B7 antigens were significantly lower, in patients with ALL compared with controls. Among patients with AML, the frequency of the HLA-B49 antigen and the HLA-DRB1*15 allele were significantly higher, whereas the frequencies of the HLA-A11 and HLA-B38 antigens were significantly lower compared with controls. The frequency of the HLA-DRB1*04 allele was also significantly higher in male patients with ALL and AML, whereas the HLA-DRB1*13 allele was found significantly less frequently in male AML and female ALL patients than in controls. To date, this is the only study to evaluate the associations between HLA molecules and leukaemia in a Turkish population with acute childhood leukaemia.

Localized residual leukaemia in bone marrow of extremities

This study aimed to confirm localized residual leukaemia in the abnormal expanded peripheral bone marrow (e-PBM) of the extremities using Tc-sulfur colloid imaging and bone marrow aspirations. Whole-body bone marrow scintigraphy was performed in 420 adult and 48 childhood leukaemia patients using Tc-sulfur colloid (370 MBq). Central bone marrow (CBM) from the iliac crest and e-PBM from the proximal epiphyseal line of the tibia were aspirated at the time of routine examination and compared. The expansion rate of the PBM in the non-remission stage of acute leukaemia was 73.1%, and it decreased to 38.4% in the complete remission stage. The most common site of PBM expansion was the epiphysis of the knee joint (74.5%). Cytological examination of the e-PBM at the complete remission stage revealed 30.9% localized residual leukaemia. The complete remission period (69+/-23 days) of PBM expansion was significantly greater than that of CBM depletion (43+/-31 days) (P<0.01). Localized residual leukaemia of the e-PBM could not be detected in the childhood acute leukaemia patients and in the patients without e-PBM. The difference in the relapse rate and time was statistically significant between patients with e-PBM (29.1%) and without e-PBM (3.5%) (P<0.01). These findings suggest that induction chemotherapy does not always have a synchronous and parallel effect on CBM and PBM. The e-PBM is less sensitive to chemotherapy and can easily exist in localized residual leukaemia. The detection of residual leukaemia in the e-PBM by bone marrow scintigraphy is very important in the treatment of leukaemia.