Acute Lymphoblastic Leukemia Phase Research Articles

Molecular characteristics and oncogenic role of CHD family genes: a pan-cancer analysis based on bioinformatic and biological analysis

Chromodomain helicase DNA-binding protein (CHD) gene family, an ATP (adenosine triphosphate) -dependent chromatin remodeler family, is involved in multiple developmental process and tumor development. However, there have been none pan-cancer analyses of this family. The expression levels, survival profiles, mutation profiles and immune infiltration of the CHD family genes from TCGA and TARGET database were analyzed using online tools or R packages. Interestingly, all types of CHD gene expressions were associated with the prognosis of Neuroblastoma, Acute lymphoblastic leukemia-Phase 3 and Acute Myeloid Leukemia (All P < 0.05). Knock down of CHD7 and CHD9 in K562 (human erythromyeloblastoid leukemia) and HEC-1-B (human endometrial adenocarcinoma) cells significantly inhibit cell proliferation and migration (P < 0.05). Proliferation, colony formation and migration assays were performed in CHD7 and CHD9 knockdown K562 and HBC-1-B cell lines. Mechanisms were also analyzed by PPI and GO ontology for our experiments. Histone modification, especially the methylation of H3K4, might be involved in CHD7 and CHD9 related oncogenesis. Through bioinformatic analysis, we showed CHD genes significantly affected the prognosis of different tumor types, including childhood tumor. Our findings provide new insights into the function and mechanism of CHD gene family, especially in CHD7 and CHD9.

ALL-621 Managing Pulmonary Embolism During Induction Phase of Acute Lymphoblastic Leukemia: A Successful Case Study

ALL-621 Managing Pulmonary Embolism During Induction Phase of Acute Lymphoblastic Leukemia: A Successful Case Study

Colo-Colic Intussusception as the Presenting Feature of Neutropenic Typhlitis during Induction Phase of Acute Lymphoblastic Leukemia in an 8-Year-Old Child

Colo-Colic Intussusception as the Presenting Feature of Neutropenic Typhlitis during Induction Phase of Acute Lymphoblastic Leukemia in an 8-Year-Old Child

A parent–child conjoint psychological intervention for children in maintenance phase of acute lymphoblastic leukemia: Feasibility and preliminary outcomes from a randomized control pilot trial

ObjectiveTo develop and test a brief Composite Intervention Module for Pre-adolescents with Acute Lymphoblastic Leukemia (CIMPALL). DesignSingle-center randomized controlled design. SettingA tertiary care center of national importance ParticipantsA total of 36 children with acute lymphoblastic leukemia in the maintenance phase of the treatment. InterventionA five-session (540 min) brief, multidomain, audiovisually aided, therapist-facilitated conjoint intervention module for children with cancer and their parents. Main outcome measuresStandardized psychological tools for children including CBCL, CPSS (Child Posttraumatic Stress Disorder Symptoms Scale), PedsQol (Pediatric Quality of Life), and NIMHANS (National Institute of Mental Health and Neurosciences) neuropsychological battery and parents including PTSD CC (Posttraumatic Stress Disorder Civilian Checklist), CHIP (Coping Health Inventory for Parents), CBS (Caregiver Burden Scale), and SRQ (Self-Reporting Questionnaire). ResultsA total of 36 patients were randomized to an experimental or a control group. Over 80% agreement was observed on indices of expert evaluation; 100% of participants found the sessions to be helpful, useful, appropriate in terms of time, duration, and place, and interventionist. The participation rate in the sessions was 94% and the study flow was smooth; 97.3% eligible candidates agreed to participate. Furthermore, 100% agreement on performance of activities was observed and the attrition rate was 5.26%. ConclusionThis pilot study presents the CIMPALL, which to the best of our knowledge is the first of its kind in India. The data suggest that the CIMPALL intervention is feasibly delivered by a clinical psychologist and that the CIMPALL intervention has an impact on important psychosocial variables for children with acute lymphoblastic leukemia and their parents.

Malnutrition is a predisposing factor for developing recurrent fever following febrile neutropenia in children with acute lymphoblastic leukemia

IntroductionThe factors that predict recurrence of fever following defervescence (DS) during febrile neutropenia (FN) episode have not been studied. The objective was to estimate the incidence and risk factors for recurrent fever (RF) in children with FN during the intensive phase of acute lymphoblastic leukemia (ALL) treatment. MethodsThe study included 113 consecutive patients diagnosed with ALL. Total of 256 FN episodes in these patients between January 2016 and June 2017 were analysed retrospectively. RF was defined as recurrent febrile event with absolute neutrophil count <500/mm3 that developed after an afebrile interval of 24 h but not exceeding 7 days following a febrile neutropenia episode. ResultsRF developed in 38/256 FNE (14.85%). Evidence of documented focus of infection was observed in 26/38 RF. Risk factors associated with development of RF were: non-remission status of bone marrow, profound neutropenia, persistent neutropenia, clinically or microbiologically documented infection, severe underweight and documented weight loss. Multivariate analysis revealed significant association between RF and non-remission status of bone marrow, profound neutropenia and severe underweight. ConclusionSevere underweight, profound neutropenia and non-remission status of bone marrow predispose the development of RF. These patients require close observation and may require prolonged administration of antibiotics irrespective of DS status.

Effect of NUDT15 on incidence of neutropenia in children with acute lymphoblastic leukemia.

6-Mercaptopurine (6-MP) is considered the backbone of therapy in the maintenance phase of acute lymphoblastic leukemia (ALL). Gene polymorphisms involved in thiopurine degradation are predictors of toxicity in patients treated with 6-MP. We investigated the effects of nucleoside diphosphate linked moiety X (nudix) type motif 15 (NUDT15) polymorphism NUDT15c.415C>T on neutropenia incidence, dose adjustment for 6-MP, and survival rates in Thai children with ALL. Children diagnosed with ALL who received 6-MP in the maintenance phase of treatment, in 2005-2016, were retrospectively enrolled. The subjects consisted of 102 patients (median age, 5.2years; 58 boys). On genetic testing 78, 22, and two patients were normal (CC), heterozygous (CT), and homozygous (TT), respectively. The incidence of neutropenia at 3months was significantly higher in the CT/TT than CC polymorphism groups (OR, 12; 95%CI: 3.781-38.085, P < 0.001). The mean dose of 6-MP at 3, 6, and 12months was significantly lower in the CT/TT versus the CC group (P < 0.001). The 5year overall survival (OS) rate for CC was 80.4%, and for CT/TT, 95.5% (P = 0.34). The 5year event-free survival (EFS) for CC and CT/TT was 75.1% and 85.7%, respectively (P = 0.17). After adjusted risk classification, no significant differences were observed for OS or EFS between the CC and CT/TT groups. Patients harboring the CT/TT polymorphism of NUDT15 had a significantly higher incidence of neutropenia during the first 3months of maintenance, resulting in significantly lower doses of 6-MP.

Endothelial Function in Children with Acute Lymphoblastic Leukemia (ALL) May Reflect the Clinical Outcome.

Endothelial dysfunction is a common feature of early complications of hemato-oncologic therapy. The aim of our study was to assess the profile of endothelial function at diagnosis time, then during initial treatment phase of acute lymphoblastic leukemia (ALL), and to verify the presence of its correlation with early clinical outcome (ECO). 28 ALL children and 18 healthy age-matched control ones were recruited. Study group was examined at baseline and at 33rd and 78th day of treatment. At each protocol step the endothelial function was assessed by measurement of sP-selectin (CD62-P), PAI-1(serpinE1), sE-selectin (CD62E), sICAM-1(sCD54), sVCAM-1(sCD106), and VEGF concentrations. Higher baseline sICAM-1 and sVCAM-1 levels and lower sP-selectin and VEGF were observed in children with ALL. sICAM-1, sVCAM-1, and sE-selectin levels were decreasing following the treatment with protocol I. Higher sE-selectin and lower baseline sICAM-1 levels were observed in children treated unsuccessfully. Lower PAI-1 levels were observed in children who survived. Higher baseline sE-selectin levels and lower sICAM-1 and VEGF were observed in children treated unsuccessfully. A decrease in sE-selectin and lower PAI-1 at the 78th day of therapy were associated with better ECO. High baseline VEGF and sE-selectin levels, significant increase in PAI-1, and low initial sICAM-1 levels are prognostics for poorer prognosis in the ALL children.

Cytomegalovirus Retinitis Occurring as a Complication of HyperCVAD Chemotherapy: Report of Two Cases

AbstractCytomegalovirus (CMV) retinitis is usually diagnosed in patients with acquired immunodeficiency syndrome and in solid organ and hematopoietic stem cell transplant recipients. It produces a characteristic necrotizing retinitis which is a sight-threatening condition in these patients. CMV retinitis occurs rarely in patients undergoing only chemotherapy, and very few cases have been reported during the maintenance phase of acute lymphoblastic leukemia (ALL) in children. We report two patients, one with ALL and the other with Burkitt’s lymphoma on HyperCVAD chemotherapy developing CMV retinitis during the course of treatment. Both patients were treated with intravenous ganciclovir, oral valganciclovir and intravitreal ganciclovir. Both patients are alive in remission at 60 and 40 months, respectively, with preservation of normal vision.

The relationship between child and caregiver sleep in acute lymphoblastic leukemia maintenance.

The purposes of this study are to describe sleep quality and sleep disturbance among caregivers of children in the maintenance phase of acute lymphoblastic leukemia (ALL) and to examine the relationship between sleep quality, child sleep disturbance, and caregiver guilt and worry. Caregivers of 68 children with ALL, ages 3 to 12years old, completed measures of caregiver guilt and worry, caregiver sleep quality, and child's developmental history and sleep habits. Demographic and treatment correlates of poor caregiver sleep were examined, and caregiver guilt and worry was tested as a moderator between child and caregiver sleep. More than half of caregivers (55.9%) reported clinically significant poor sleep and less than 40% were obtaining adequate sleep durations. Caregiver sleep was significantly related to child age at diagnosis, child sleep, and caregiver guilt and worry. Caregiver guilt and worry did not moderate the relationship between child sleep and caregiver sleep. Poor sleep is common in caregivers of children with cancer. Further research on the timing of sleep interventions and the most effective intervention targets are needed to maximize caregiver functioning during a child's cancer treatment. Targeted interventions seeking to improve caregiver sleep should be directed towards caregivers of children diagnosed in early childhood, caregivers of children with poor sleep, and caregivers with high guilt and worry.

The Relation between Plasma Levels of Thrombomodulin and Endothelial Dysfunction in Syrian Children with Acute Lymphoblastic Leukemia

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancies, representing nearly one-third of all pediatric cancers. Thrombomodulin is a membrane glycoprotein expressed on endothelial cells, Its plasma level depends on the integrity of the endothelium. Soluble thrombomodulin is derived from injured endothelial cells or proteolytically cleaved from thrombomodulin by proteases. In the past, the endothelium was considered to be inert, described as a 'layer of nucleated cellophane', with only non-reactive barrier properties. However, it is now becoming clear that endothelial cells actively and reactively participate in hemostasis and immune and inflammatory reactions. They regulate vascular tone via production of nitric oxide, endothelin and prostaglandins. Severe endothelial dysfunction is present during the acute phase of acute lymphoblastic leukemia and it result from the disease itself, from treatment, or from other conditions (e.g. sepsis). Objective:The aim of this study was to determine the level of serum soluble thrombomodulin as a marker of endothelial activation in children with ALL at time of diagnosis and after the chemotherapy. Methods and Materials: A case - control study included Thirty patients with ALL and twenty healthy children. We analyzed serum soluble thrombomodulin levels by enzyme-linked immunosorbent assay. Results: In children with acute lymphoblastic leukemia, there was a significant increase in soluble thrombomodulin levels during the acute phase of the disease and during treatment. Conclusion: severe endothelial dysfunction is present during the acute phase of ALL and during treatment and appears to result from the disease itself and from the treatment.

Prognostic value of plasma levels of thrombomodulin and von Willebrand factor in Egyptian children with acute lymphoblastic leukemia

Acute lymphoblastic leukemia is the most common childhood malignancies, representing nearly one-third of all pediatric cancers. Thrombomodulin is a membrane glycoprotein in the vascular endothelium. Its plasma level depends on the integrity of the endothelium. Soluble thrombomodulin is derived from injured endothelial cells or proteolytically cleaved from thrombomodulin by proteases. Von Willebrand factor is a blood glycoprotein involved in homeostasis. Its plasma level increases in neoplastic diseases and arises from adverse changes in the endothelium. Severe endothelial dysfunction is present during the acute phase of acute lymphoblastic leukemia. Plasma levels of von Willebrand factor and soluble thrombomodulin have been used as indexes of endothelial dysfunction. The aim of this study was to assess serum soluble thrombomodulin and von Willebrand factor levels in children with acute lymphoblastic leukemia during acute phase of the disease to assess their potential prognostic value. Forty patients with acute lymphoblastic leukemia included 26 males and 14 females with their ages ranged from 2 to 10 years and 20 healthy children of matched age and sex were included in this study. We analyzed serum soluble thrombomodulin and von Willebrand factor levels by enzyme-linked immunosorbent assay. In children with acute lymphoblastic leukemia, there was a significant increase in soluble thrombomodulin, and von Willebrand factor levels during the acute phase of the disease. Children with an unfavorable outcome had higher levels of thrombomodulin and von Willebrand factor levels. Serum thrombomodulin and von Willebrand factor levels as a parameter of endothelial dysfunction during the acute phase of acute lymphoblastic leukemia might represent an additional prognostic marker in childhood acute lymphoblastic leukemia.

Sequential acquisition of IgH and TCR rearrangements during the preleukemic phase of acute lymphoblastic leukemia in an adolescent patient

Acute lymphoblastic leukemia (ALL) can be preceded by a prodromal phase of bone marrow failure. In serial trephine biopsies in a girl with acquired bone marrow hypoplasia, we have identified a monoclonal B-cell precursor population characterized by a clone-specific IgH-FR3 gene rearrangement. Progression to ALL more than 4 months later was accompanied by acquisition of an additional T-cell receptor rearrangement. Thus, hypoplastic pre- and overt leukemia share a common clonal origin. Prospective biobanking and extended molecular analysis can help to better understand the nature and sequence of genetic events during progression of a covert (pre)leukemic clone.

Terminal deoxynucleotidyltransferase distribution in neoplastic and hematopoietic cells.

In the present study, terminal deoxynucleotidyltransferase was examined in the peripheral blood and (or) bone marrow of 115 children with a variety of neoplastic, hematologic, and other unrelated disorders. Terminal deoxynucleotidyltransferase activity was present at 4.08+/-0.74 U/108 cells in 23 morphologicall normal bone marrow samples from childhood controls. Terminal transferase was present at greater than 23 U/108 nucleated cells and at greater than31 U/108 blasts in the bone marrow of all children with acute lymphoblastic leukemia studied at initial diagnosis and at disease relapse. Terminal deoxynucleotidyltransferase was detectable at low levels, less than 7.5 U/108 cells, in all remission marrow smaples. Bone marrow terminal transferase activity was markedly elevated in all untreated acute lymphoblastic leukemia patients, whereas low levels which were difficult to interpret were present in the peripheral blood samples of two patients at diagnosis and six patients at relapse who had low absolute lymphoblast counts. Because of greater variation in the lymphoblast content of peripheral blood, bone marrow assays are more reliable in detecting disease activity. Marrow terminal deoxynucleotidyltransferase values obtained during the active phase of acute lymphoblastic leukemia were significantly greater than those found in other types of leukemia, bone marrow malignancies, and hematologic disorders. Terminal transferase determinations in blast cells of two patients with leukemic conversion of non-Hodgkin's lymphoma and in tumor cells from one patient with Burkitt's lymphoma were within the control range. These dat further define the usefulness of terminal deoxynucleotidyltrnasferase assay in the differentiation and classication of hematologic malignancies.

Unusal complications of pentamidine in the treatment of Pneumocystis carinii pneumonia

A 3-year-old girl, during a remission phase of acute lymphoblastic leukemia, developed <i>Pneumocystis carinii</i> pneumonia. The infection was treated successfully with pentamidine, but she developed toxic epidermal necrolysis and azotemia. Acute tubular necrosis of the kidney was found at autopsy.