Pediatric Acute Leukemia Patients Research Articles

Analysis of Pulmonary Complications in Pediatric Acute Lymphocytic Leukemia Patients following Three Years of Chemotherapy Treatment: A Cross-Sectional Study

Background: This study aimed to investigate the pulmonary side effects of chemotherapy drugs in children with Acute Lymphocytic Leukemia (ALL) three years after treatment. The results could be of great help in managing lung complications in pediatric oncology patients. Materials and Methods: This cross-sectional descriptive study included 50 patients (22 males and 28 females) with ALL. Data were collected from patients' files, including age, sex, duration of illness, last dose of chemotherapy, and medications such as PEG.Asparginas, Cyclophosphamid, thioguanine, Dexamethason, cytarabin, cytosin.arabinosid, vincristine, mercaptopurine, and methotrexate. Pulmonary function tests (Forced Vital Capacity (FVC), FEV1 (Forced Expiratory Volume in the first second)) were assessed by spirometry. Results: Out of 50 patients, 47 (94%) did not have pulmonary disorders, while 3 (6%) had pulmonary dysfunction. Forty-seven patients (94%) did not have respiratory symptoms. FVC results showed that 45 patients were normal, and 5 were abnormal. Similarly, 45 patients had normal FEV1, and 5 had abnormal results. Spirometry results were normal in 45 patients and abnormal in 5. A significant relationship was found between the use of these drugs in different doses and spirometry results, recurrence rate, and pulmonary complications (P <0.05). No significant relationship was observed between pulmonary dysfunction and other drugs (P> 0.05). No correlation was found between pulmonary complications due to chemotherapy with duration of chemotherapy, patient age, and patient gender (P> 0.05). Conclusion: Pulmonary dysfunction and respiratory syndrome were observed in 6% of patients receiving chemotherapy. A significant relationship was found between the frequency of pulmonary and respiratory complications with some chemotherapy drugs in children with ALL. Further research is needed to optimize treatment strategies and minimize lung complications in pediatric oncology patients.

Evaluation of FOXP3 and IL10 as immunosuppressant markers in pediatric acute lymphocytic leukemia patients in Iraq

Background. Increased FOXP3+ Treg levels in the TME were positively correlated with a worse prognosis in certain cancer patients. FOXP3 was significantly overexpressed in pediatric B-ALL patients, and this overexpression was associated with a worse prognosis and increased risk of disease relapse. It is unknown if children that have the condition would have different prenatal immune development. This study investigates the relationship between IL10, and immunological development in pediatric ALL. Methods. The 70 blood samples from children between the ages of 2 and 14 for both sexes were obtained from patients with Acute lymphoblastic leukemia. Furthermore, this study comprised 54 healthy controls. Included in this study, FOXP3 expression on leukemic blast cells were assessed using flow cytometry. And IL10 were assessed using ELISA test. Results. Increase of FOXP3 cells was noticed in children with ALL compared to healthy individuals with significant increase of FOXP3 (mean ± SD, 91.156 ± 12.255 vs. 14.88 ± 7.897pg/ml (p <0.05). In light of these findings, significant differences in the levels of FOXP3, which was higher in induction than consolidation stage of chemotherapy (mean ± SD, 91.24± 11.078vs. 86.35±5. 16.66) pg/ml (p <0.05). Additionally, it was found that the prevalence of lymphoblast that express FOXP3 was notably higher in the HR group in contrast to the SR group (mean ± SD, 95.52± 5.79 vs. 42.88± 31.38) pg/ml (p <0.05). Following these findings, significant differences in the levels of FOXP3 was higher in relapse than new diagnosis chemotherapy stage (mean ± SD, 95.66± 5.167 vs. 91.035±5. 13.177) pg/ml (p<0.05). On the other hand, children with ALL were also found to have significantly higher levels of IL10 in the current study when compared to healthy controls (mean ± SD, 0.146 ± 0.145 vs. 0.076 ± 0.10 pg/ml (P <0.05). Following these findings, significant differences in the levels of IL10 was higher in consolidation than induction chemotherapy stage (mean ± SD, 0.165± 0.084 vs.0 .0720±.018) pg/ml (p <0.05), the serum levels of IL-10 were evaluated in the two groups: new diagnosis and relapse cases. As in the description profile, serum levels are higher in the relapse group with a highly significant difference. For the parameter IL10 (P ≤0.05). As for he mean level, it was as follows: of IL10 (0.130) pg/ml and (0.216) pg/ml, with (P-value =0.0001) in new diagnosis and relapse receptivity. Conclusions. According to our findings, B-ALL patients have significant amounts of both FOXP3 and IL10. This pilot study provides a novel way to look into the process mediating the appearance of these markers in a greater number of B-ALL patients at various stages of their treatment.

Increased donor inhibitory KIR are associated with reduced GVHD and improved survival following HLA-matched unrelated donor HCT in paediatric acute leukaemia.

Killer immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play an important role in natural killer cell-mediated effects after haematopoietic stem cell transplantation (HCT). Previous work has shown that accounting for known KIR-KIRL interactions may identify donors with optimal NK cell-mediated alloreactivity in the adult transplant setting. Paediatric acute leukaemia patients were retrospectively analysed, and KIR-KIRL combinations and maximal inhibitory KIR ligand (IM-KIR) scores were determined. Clinical outcomes were examined using a series of graphs depicting clinical events and endpoints. The graph methodology demonstrated that prognostic variables significant in the occurrence of specific clinical endpoints remained significant for relevant downstream events. KIR-KIRL combinations were significantly predictive for reduced grade 3-4 aGVHD likelihood, in patients transplanted with increased inhibitory KIR gene content and IM-KIR = 5 scores. Improvements were also observed in associated outcomes for both ALL and AML patients, including relapse-free survival, GRFS and overall survival. This study demonstrates that NK cell KIR HLA interactions may be relevant to the paediatric acute leukaemia transplant setting. Reduction in aGVHD suggests KIR effects may extend beyond NK cells. Moving forward clinical trials utilizing donors with a higher iKIR should be considered for URD HCT in paediatric recipients with acute leukaemia to optimize clinical outcomes.

Feasible diet and circadian interventions reduce invivo progression of FLT3-ITD-positive acute myeloid leukemia.

Acute myeloid leukemia (AML) with an internal tandem duplication in the fms-like tyrosine kinase receptor 3 gene (FLT3-ITD) is associated with poor survival, and few studies have examined the impact of modifiable behaviors, such as nutrient quality and timing, in this subset of acute leukemia. The influence of diet composition (low-sucrose and/or low-fat diets) and timing of diet were tested in tandem with anthracycline treatment in orthotopic xenograft mouse models. A pilot clinical study to test receptivity of pediatric leukemia patients to macronutrient matched foods was conducted. A role for the circadian protein, BMAL1 (brain and muscle ARNT-like 1), in effects of diet timing was studied by overexpression in FLT3-ITD-bearing AML cells. Reduced tumor burden in FLT3-ITD AML-bearing mice was observed with interventions utilizing low-sucrose and/or low-fat diets, or time-restricted feeding (TRF) compared to mice fed normal chow adlibitum. In a tasting study, macronutrient matched low-sucrose and low-fat meals were offered to pediatric acute leukemia patients who largely reported liking the meals. Expression of the circadian protein, BMAL1, was heightened with TRF and the low-sucrose diet. BMAL1 overexpression and treatment with a pharmacological inducer of BMAL1 was cytotoxic to FLT3-ITD AML cells. Mouse models for FLT3-ITD AML show that diet composition and timing slows progression of FLT3-ITD AML growth invivo, potentially mediated by BMAL1. These interventions to enhance therapy efficacy show preliminary feasibility, as pediatric leukemia patients responded favorable to preparation of macronutrient matched meals.

THU150 The Association Between Glycated Albumin And HbA1c In Pediatric Acute Leukemia Patients

Abstract Disclosure: S. Sim: None. M. Ahn: None. B. Suh: None. Introduction: Traditionally, HbA1c has been used as a preferred glycemic index in diabetes patients. However, as many acute leukemia patients often present with anemia and/or pancytopenia, HbA1c may not accurately represent blood glucose level in this group. Glycated albumin represents the average level of blood glucose in recent 2-3 weeks, independent of red blood cell life. In this study, we aim to evaluate the usefulness of glycated albumin as glycemic monitoring index in pediatric patients diagnosed with acute leukemia. Methods: We performed retrospective analysis of a total of 206 pediatric patients from The Seoul St. Mary’s hospital, Catholic university of Korea. Medical records of 25 patients diagnosed with type 2 DM and 66 patients with acute leukemia were investigated for serum glycated albumin, HbA1c, fasting blood glucose level, and demographic data such as sex, age, height, weight and BMI z-scores. 115 children and adolescents who visited our outpatient center for routine child health examination were enrolled as the control group. Results: The median serum glycated albumin levels were 12.4%, 19.1% for acute leukemia and T2DM patients. HbA1c and fasting blood glucose levels, 5.3% and 7.6%, 92mg/dl and 129mg/dl respectively, also differed in the two groups. All glycated albumin, HbA1c and fasting blood glucose level did not appear different in between the control and acute leukemia group. In type 2 DM patients, glycated albumin and HbA1c showed positive correlations (r=0.926, p<0.01). Fasting blood glucose level was also positively correlated to glycated albumin (r=0.821, p<0.001) and HbA1c (r=0.773, p<0.001). While glycated albumin did not appear related to HbA1c in the normal control group (r=-0.02, p=0.824), patients with acute leukemia also revealed a positive correlation between glycated albumin and HbA1c (r=0.253, p=0.04). Glycated albumin was negatively related to BMI z-scores in the control group (r=0.554, p<0.001); however, the level showed no correlation to BMI z-scores in acute leukemia group and in T2DM patients (r=-0.133, p=0.286 and r=-0.292, p=0.156). HbA1c level was positively related to BMI z-scores in the control group (r=0.241, p=0.01) and showed no relations in the other two groups. Regression analysis found glycated albumin to be positively correlated to HbA1c both in acute leukemia pediatric patients and T2DM patients even when adjusted for age, sex and BMI z-score (p=0.039, p=0.007). Conclusion: In acute leukemia patients, glycated albumin may be a complementary parameter of glycemic status as in diabetic patients. Presentation: Thursday, June 15, 2023

Investigation of Treg in Pediatric Acute Lymphocytic Leukemia Patients during Chemotherapy Stages and Relapse

A cross-sectional case-control study has been carried out on Treg cells in pediatric acutelymphoblastic leukemia (ALL) patients admitted to Al-Basrah Children Teaching SpecialtyHospital from November 2022 to May 2023. A total number of 70 patients (25 newlydiagnosed, 12 relapse, 21 during induction, and 12 during consolidation chemotherapy)were enrolled, aged 2 to 14 years, along with 54 healthy controls who were the sameage and gender as the study. Blood samples were collected from all participants for flowcytometer applied to study Treg cell markers. The results of the current study showedthat the highest percentage of ALL patients was in the age group of 2 to 5 years 54.3%followed by age group 6 to 12 years 41.4%, whereas the lowest percentage was in patientsolder than 12 year 4.3% (p-value 0.802). The p-value was considered significant if it is ?0.05 and highly significant if ? 0.001. Regarding the flow cytometry analysis results forCD3, CD4 and CD25, ALL patients had a significantly higher mean of these markers thanthe control group (p-value ? 0.005). A slightly higher level CD4 was noted in new casescompared to relapse cases, and induction and consolidation (p = 0.080). The results ofTreg levels cells in relapse, induction, consolidation and new diagnosis cases. On the otherhand, demonstrate higher levels in the relapse group, with highly significant differencesfor the two parameters: CD3–CD25 (p ? 0.005). The level of CD25 displayed a highlysignificant difference when comparing induction with consolidation (p ? 0.005). Fromthis study, we conclude that the immunological marker (CD 25) specifically provided themost highly significant value as immunosuppression parameters in all patients, whereaschemotherapy represents the key risk factor for immunosuppression in all patients variessignificantly among chemotherapy stages, with consolidation having the most impact.This effect may be due to the high dose of MTX.Background: T regulatory cells (Tregs) are immunosuppressive cells that can be dividedinto numerous subsets. Tregs comprise a small but heterogeneous population, which thephenotype may identify as CD3+CD4+CD25+. They play a crucial role in the preservation of immunological homeostasis and self-tolerance. They also play important roles In the control of cancer immunity. Tregs mayalso be important in acute leukemia.Patients and Methods: A7 0 blood samples of both sexes with the age range 2 to 14 years old were collected from patients withALL. Additionally, this investigation included 54 healthy controls included in CD3, CD4 and CD25 expression on leukemicblast cells were assessed using flow cytometry.Results: Increased values of CD3+CD25+ T cells were observed in children with all in comparison to healthy controls withsignificant differences in the markers for Tregs (mean ± SD, 14.971 ± 11.06 vs. 5.680 ± 2.96 pg/mL) (p <0.05).Following these findings, significant differences in the levels of CD25 was higher in consolidation than in the inductionchemotherapy stage (mean ± SD, 17.657 ± 13.890 vs. 5.100 ± 5.1438) pg/mL (p <0.05), children with all were also found tohave significantly higher levels of CD4 in the current study when compared to healthy controls (mean ± SD, 29.261 ± 13.828vs. 28.3465 ± 11.17146) pg/mL (p <0.05), Table 2.According to the chemotherapy stage there were significant significant differences in the levels of CD25 in the relapse state,which was higher than the chemotherapy stage for new diagnosis (mean ± SD, 22.185 ± 15.148 vs. 13.649 ± 5. 83) pg/mL (p<0.05). A further finding was that the frequency of lymphoblast that expresses CD25 was considerably higher in the high-riskgroup compared to the standard risk group (mean ± SD, 15.75 ± 4.74 vs. 7.92 ± 1.012) pg/mL (p <0.05) Table 3.Conclusion: Chemotherapy represents the interested immunosuppression risk factor in ALL patients. There is a significantvariation among chemotherapy stages in ALL patient immunosuppression. Consolidation represent the high influence on ALLpatient in immune suppression may be related to the high dose of MTX.

Access to Chimeric Antigen Receptor T Cell Clinical Trials in Underrepresented Populations: A Multicenter Cohort Study of Pediatric and Young Adult Acute Lymphobastic Leukemia Patients

Chimeric antigen receptor T cell (CAR-T) therapy is a promising approach to improve survival for children and adults with relapsed/refractory (r/r) B cell acute lymphoblastic leukemia (B-ALL), but these clinical trials might not be equally accessible to patients of low socioeconomic status (SES) or to patients from racial or ethnic minority groups. We sought to describe the sociodemographic characteristics of pediatric and adolescent and young adult (AYA) patients enrolled in CAR-T clinical trials and to compare these characteristics to those of other patients with r/r B-ALL. We conducted a multicenter retrospective cohort study at 5 pediatric consortium sites to compare the sociodemographic characteristics of patients treated and enrolled in CAR-T trials at their home institution, other patients with r/r B-ALL treated at these sites, and patients referred from an external hospital for CAR-T trials. The patients were age 0 to 27 years with r/r B-ALL treated at 1 of the consortium sites between 2012 and 2018. Clinical and demographic data were collected from the electronic health record. We calculated distance from home to treating institution and assigned SES scores based on census tract. Among the 337 patients treated for r/r B-ALL, 112 were referred from an external hospital to a consortium site and enrolled in a CAR-T trial and 225 were treated primarily at a consortium site, with 34% enrolled in a CAR-T trial. Patients treated primarily at a consortium site had similar characteristics regardless of trial enrollment. Lower proportions of Hispanic patients (37% versus 56%; P = .03), patients whose preferred language was Spanish (8% versus 22%; P = .006), and publicly insured patients (38% versus 65%; P = .001) were referred from an external hospital than were treated primarily at a consortium site and enrolled in a CAR-T trial. Patients who are Hispanic, Spanish-speaking, or publicly insured are underrepresented in referrals from external hospitals to CAR-T centers. External provider implicit bias also may influence referral of these patients. Establishing partnerships between CAR-T centers and external hospital sites may improve provider familiarity, patient referral, and patient access to CAR-T clinical trials.

DNA Damage Response-Related Proteins Are Prognostic for Outcome in Both Adult and Pediatric Acute Myelogenous Leukemia Patients: Samples from Adults and from Children Enrolled in a Children's Oncology Group Study.

The survival of malignant leukemic cells is dependent on DNA damage repair (DDR) signaling. Reverse Phase Protein Array (RPPA) data sets were assembled using diagnostic samples from 810 adult and 500 pediatric acute myelogenous leukemia (AML) patients and were probed with 412 and 296 strictly validated antibodies, respectively, including those detecting the expression of proteins directly involved in DDR. Unbiased hierarchical clustering identified strong recurrent DDR protein expression patterns in both adult and pediatric AML. Globally, DDR expression was associated with gene mutational statuses and was prognostic for outcomes including overall survival (OS), relapse rate, and remission duration (RD). In adult patients, seven DDR proteins were individually prognostic for either RD or OS. When DDR proteins were analyzed together with DDR-related proteins operating in diverse cellular signaling pathways, these expanded groupings were also highly prognostic for OS. Analysis of patients treated with either conventional chemotherapy or venetoclax combined with a hypomethylating agent revealed protein clusters that differentially predicted favorable from unfavorable prognoses within each therapy cohort. Collectively, this investigation provides insight into variable DDR pathway activation in AML and may help direct future individualized DDR-targeted therapies in AML patients.

Poor Outcomes Among Pediatric Non-Down Syndrome Acute Megakaryocytic Leukemia Patients Irrespective of Receipt of Hematopoietic Stem Cell Transplant

Poor Outcomes Among Pediatric Non-Down Syndrome Acute Megakaryocytic Leukemia Patients Irrespective of Receipt of Hematopoietic Stem Cell Transplant

Pediatric non-Down's syndrome acute megakaryoblastic leukemia patients in China: A single center's real-world analysis.

Non-Down’s syndrome acute megakaryocytic leukemia (non-DS-AMKL) is a subtype of childhood acute myeloid leukemia (AML), whose prognosis, prognostic factors and treatment recommendations have not yet to be defined in children. We conducted a retrospective study with 65 newly diagnosed non-DS-AMKL children from August 2003 to June 2020 to investigate the clinical impact of factors and clinical outcome. Among all 65 patients, 47 of them were treated at our center who received three different regimens due to time point of admission (CAMS-another, CAMS-2009 and CAMS-2016 protocol), and the efficacy were compared. Patients with newly diagnosed non-DS-AMKL accounted for 7.4% of pediatric AML cases. The median age of the patients was 18 months at diagnosis, and over 90% of them were under three-years-old. The overall survival (OS) rates were 33.3% ± 1.7%, 66.7% ± 24.4% and 74.2% ± 4.0% for three groups (CAMS-another, CAMS-2009 and CAMS-2016 regimen), respectively. In CAMS-2016 group, the complete remission (CR) rate after induction was 67.7% (21/31), while the total CR rate after all phases of chemotherapy was 80.6% (25/31). The 2-year survival probability did not significantly improve in patients underwent HSCT when compared with non-HSCT group (75.0% ± 4.7% vs. 73.9% ± 4.6%, p=0.680). Those who had a “dry tap” during BM aspiration at admission had significantly worse OS than those without “dry tap” (33.3% ± 8.6% vs. 84.0% ± 3.6%, p=0.006). Moreover, the results also revealed that patients with CD34+ had significantly lower OS (50.0% ± 6.7% vs. 89.5% ± 3.5%, p=0.021), whereas patients with CD36+ had significantly higher OS than those who were negative (85.0% ± 4.0% vs. 54.5% ± 6.6%, p=0.048). In conclusion, intensive chemotherapy resulted in improved prognosis of non-DS-AMKL children and subclassification may base on “dry tap” and immunophenotypic. Although some progress has been made, outcomes of non-DS-AMKL children remain unsatisfactory, especially in HSCT group, when compared with other AML types.

Genetic variation in FOXP3 and ROR-γ genes in pediatric acute lymphocytic leukemia (ALL) patients: correlation with associated cytokines

BackgroundFOXP3 and ROR-γ genes are master regulators of the Treg and Th17 differentiation, respectively. This work was planned to investigate the impact of FOXP3 (rs3761548C/A and rs3761549C/T) and ROR-γ (rs9017A/G & rs9826A/G) gene polymorphism on the vulnerability of pediatric Egyptians to acute lymphoblastic leukemia (ALL). Furthermore, we evaluated the impact of these genetic variations on Treg/Th17-related cytokines.MethodsFOXP3 SNPs were genotyped using PCR-based restriction fragment length polymorphism (PCR-RFLP), while ROR-γ SNPs polymorphism were performed by PCR-sequence-specific primer (PCR-SSP). An Enzyme-linked immunosorbent assay (ELISA) was used to assess the levels of Treg/Th17 associated cytokines on 128 ALL children and 124 healthy donors.ResultsCompared to controls, patients had a significant increase (p < 0.01/p < 0.05) in FOXP3rs3761548CC genotype and a significant decrease (p < 0.001/p < 0.01) inrs3761548CA genotype. A significant elevation (p < 0.001/p < 0.01) in ROR-γ rs9017AA genotype and a significant reduction (p < 0.01/p < 0.05) in rs9017AG genotype were detected in ALL patients versus controls. An insignificant change in FOXP3 (rs3761549C/T) and ROR-γ (rs9826A/G) genotypes was demonstrated between both groups. ROR-γ GG and GA haplotypes were significantly decreased (p < 0.05/p < 0.05; p < 0.05/p < 0.05) in ALL subjects compared to healthy ones. Relapsed patients had a significantly higher (p < 0.05/P < 0.05) frequency of FOXP3 rs3761548CA genotype than non-relapsed subjects. ROR-γ rs9017AG and rs9826GG genotypes might be associated with the increase in IL-23 plasma level.ConclusionsOur preliminary data provided evidence for the impact ofFOXP3 (rs3761548C/A) and ROR-γ (rs9017A/G) gene polymorphisms and the occurrence of ALL in Egyptian children. Another large-scale prospective study should be conducted to validate these findings.

Respiratory Viral Infections in Pediatric Acute Leukemia Patients Presenting with Febrile Neutropenia in a Tertiary Hospital in Ankara, Turkey

Background: The prevalence and roles of respiratory viral pathogens in pediatric acute leukemia patients with febrile neutropenia is not well understood and laboratory tests to detect viral agents are not a routine practice in the investigation of these patients.Patients and methods: The medical records of 50 neutropenic episodes in pediatric acute leukemia patients in the Hacettepe University Children’s hospital, Ankara-Turkey, were reviewed. Blood samples were obtained for blood culture, aspergillus antigen and other routine tests. Nasopharyngeal aspirate samples were collected and transferred to the laboratory in a viral transport medium. Therapy for febrile neutropenia was initiated according to our institution’s protocols.Results: Fifty (50) consecutive febrile neutropenic episodes in 44 pediatric ALL and AML patients were included in the study between 1st October 2009 and 31st August 2010. Microbiologically documented infections were found in 36% of the episodes, clinically documented infections in 16% of the episodes and 48% of the episodes were accepted as Fever of Unknown Origin. Twenty-two percent (22%) of the microbiologically documented infections were due to viral agents, 56 % were due to Gram positive bacteria, 21% were due to Gram negative bacteria (E. coli) and only one episode of fungemia was documented.Conclusions: Fever of Unknown Origin constituted nearly 50% of the febrile neutropenic episodes in this study despite the availability of advanced laboratory diagnostic methods. Among the episodes with microbiologically documented infections, bacterial pathogens were especially common. Presenting complaints like cough and rhinorrhea are not specific to a viral etiology and care should be taken not to miss potentially threatening bacterial pathogens in such episodes.

The Evaluation of Central Venous Catheter-related Complications in Pediatric Acute Leukemia Patients: Single Center Experience.

Central venous catheters (CVCs) are important for maintenance of childhood leukemia treatment but CVCs may develop complications. The aim of this study was to retrospectively evaluate the CVC-related complication rate, complication types, and outcome in children with acute leukemia. Complications developing in 310 CVCs (ports n=250, Hickman catheters n=60) inserted in 262 patients were evaluated. A total of 225,296 catheter days were screened. Median (range) CVC in-dwelling time was 661.5 (1 to 2636) days. In total, 157 complications developed of which 91 (58%) were infectious complications, 35 (22.3%) were vascular, 19 (12.1%) were surgical, and 12 (7.6%) were mechanical. Hickman catheters had a higher complication rate and were more prone to mechanical complications ( P <0.01) but there was no difference for other complications. A lower absolute neutrophil count at insertion was observed in children with infectious complications ( P <0.01). Seventy-eight of 136 catheters (57.3%) had to be removed prematurely. The overall complication rate was 0.65 per 1000 catheter days. In multivariate analysis, relapse leukemia, Hickman catheter and low absolute neutrophil count increased complication risk by 4.00, 1.97, and 1.92 times, respectively. Five (1.9%) deaths occurred because of catheter complications. Safe use of CVCs can be improved by early detection of complications and an experienced catheter care team.

Therapeutic Outcomes of Pediatric Acute Myeloblastic Leukemia Patients at a Tertiary Hospital in Bandung, Indonesia

Background: Acute myeloblastic leukemia (AML) is a subtype of leukemia characterized by myeloid infiltration into the bone marrow, blood, and other tissues. AML ranks 5th malignancy in children and the prognosis is poor. After chemotherapy, the outcomes vary. Therefore, this study aimed to provide further insight into the therapeutic outcomes of pediatric AML patients. Methods: This study was conducted with a cross-sectional descriptive method. The data were obtained from the medical records of children diagnosed with AML at the Department of Child Health of Dr. Hasan Sadikin General Hospital in 2017–2019 with the total sampling method. Data including age at determination, gender, laboratory values including hemoglobin, leukocyte, thrombocyte as well as blast cell count on peripheral blood smear were collected. Also, the bone marrow punctures gathered were clustered based on the French-American-British (FAB) classification. Data were presented in tables. Results: In total, 46 data of AML patients were retrieved, with the age category at first diagnosis was &gt;5–12 years (48%) and predominantly males (63%), children with moderate anemia (41%), leukocytosis (35%), severe thrombocytopenia (46%), and blast cell count ≥20% (83%). AML-M2 was the most common subtype (30.4%). The majority of patients (91%) underwent chemotherapy and most (45%) patients died during chemotherapy Conclusion: The outcome of AML therapy among children is mostly poor, and particularly die during chemotherapy. Early detection and follow-up of patients to continue therapy are important aspects to reduce the mortality rate of AML.

Post-Transplantation Cyclophosphamide-Based Haploidentical versus Matched Unrelated Donor Peripheral Blood Hematopoietic Stem Cell Transplantation Using Myeloablative Targeted Busulfan-Based Conditioning for Pediatric Acute Leukemia

The use of haploidentical related donors (HRDs) is a common alternative donor strategy used when matched sibling or unrelated donors are not available for hematopoietic stem cell transplantation (HSCT). However, there have been no studies comparing HRD HSCT with post-transplantation cyclophosphamide (PTCy) and matched unrelated donor (MUD) HSCT with antithymocyte globulin using similar busulfan-based myeloablative conditioning regimens in pediatric acute leukemia. Here we compared the outcomes in children and adolescents with high-risk acute leukemia who underwent HRD HSCT with PTCy (n=35) or MUD HSCT (n=45) after targeted busulfan-based myeloablative conditioning using intensive pharmacokinetic monitoring. The median duration of follow-up was 3.7 years in the HRD group and 4.6 years in the MUD group. No engraftment failure was observed in either group. There were no significant between-group differences in the cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) (34.3% versus 48.9%; P=.142), grade III-IV acute GVHD (2.9% versus 8.9%; P=.272), moderate to severe chronic GVHD (11.4% versus 18.3%; P=.417), relapse (25.6% versus 28.0%; P=.832), and nonrelapse mortality (0% versus 2.2%; P=.420). The 3-year severe chronic GVHD-free/relapse-free survival (GRFS), leukemia-free survival (LFS), and overall survival (OS) rates in the HRD and MUD groups were 62.9% (95% confidence interval [CI], 45.8% to 80.0%) versus 49.8% (95% CI, 34.9% to 64.7%; P=.318), 74.4% (95% CI, 58.7% to 90.1%) versus 67.5% (95% CI, 53.4% to 81.6%; P=.585), and 88.6% (95% CI, 78.0% to 99.2%) versus 83.7% (95% CI, 72.5% to 94.9%; P=.968), respectively. In a subgroup analysis of patients with acute lymphoblastic leukemia (HRD, n=17; MUD, n=26), the 3-year GRFS, LFS, and OS rates in the HRD and MUD groups were 49.4% (95% CI, 24.3% to 74.5%) versus 39.5% (95% CI, 19.7% to 59.3%; P=.601), 61.8% (95% CI, 37.5% to 86.1%) versus 63.6% (95% CI, 44.4% to 82.8%; P=.872), and 82.4% (95% CI, 64.4%, 100%) versus 84.2% (95% CI, 70.1% to 98.3%; P=.445), respectively. In patients with acute myelogenous leukemia (AML) (HRD, n=16; MUD, n=16), the 3-year GRFS, LFS, and OS rates in the HRD and MUD groups were 80.8% (95% CI, 61.2% to 100%) versus 61.9% (95% CI, 37.8% to 86.0%; P=.326), 87.1% (95% CI, 70.2% to 100%) versus 73.9% (95% CI, 51.8% to 96.0%; P=.478), and 93.8% (95% CI, 81.8% to 100%) versus 85.6% (95% CI, 67.0% to 100%; P=.628), respectively. Although the difference was not statistically significant and the number of patients was small, the promising outcomes of HRD HSCT in AML patients were encouraging. Our results demonstrate that HRD HSCT with PTCy using a targeted busulfan-based myeloablative conditioning regimen has outcomes similar to those of MUD HSCT with antithymocyte globulin. HRD HSCT with PTCy could be a feasible option for pediatric high-risk acute leukemia patients who lack an HLA-matched related or unrelated donor.

Study of Factors Affecting the Time to Diagnosis and Treatment in Pediatric Acute Leukemia Patients- A study from India

Timely diagnosis and early initiation of treatment of acute leukemia in children improve survival. Our study aimed to identify the factors associated with delayed diagnosis of acute leukemia in children.&nbsp;A prospective observational study was done at a tertiary care Superspeciality hospital in Northern India. The study included 100 children aged 0&ndash;12 years over 18 months with the diagnosis of acute leukemia. A mixed-methods technique was used, combining important variables with qualita

The Role of ETO and CtBP1 in CBFA2T3-GLIS2 Mediated Transcriptional Regulation and Leukemogenesis

CBFA2T3-GLIS2 is the most prevalent fusion oncogene in pediatric acute megakaryoblastic leukemia patients without Down syndrome and is associated with an event free survival of only 8%. A cryptic inversion event on chromosome 16 joins the three nervy homology regions (NHR) of CBFA2T3 to the five zinc fingers of GLIS2. This configuration enables the encoded chimeric transcription factor to bind GLIS2 consensus sequences throughout the genome and recruit transcriptional activators and repressors to alter gene expression and enhance self-renewal capability. Few cooperating mutations have been identified in patients harboring this fusion which suggests it is the sole oncogenic driver. The molecular mechanism by which CBFA2T3-GLIS2 drives leukemogenesis is not fully understood. Identification of components critical to the transcriptional complex and their role in gene regulation may reveal novel therapeutic targets to improve patient outcomes. Studies on the wild type CBFA2T3 and GLIS2 proteins have demonstrated interactions with the transcriptional regulators ETO and CtBP1 respectively. Further p300 has been shown to play a role in transcriptional regulation imparted by both transcription factors. We therefore hypothesize the fusion promotes transcriptional activation when the histone acetyltransferase p300 and the transcription factor ETO are recruited through NHR1 and NHR2, respectively. When the co-repressor CtBP1 is recruited through the PXDLS motif, located in the GLIS2 portion of the fusion, transcriptional repression predominates. Association of these co-factors with the fusion was confirmed through co-immunoprecipitations. Site-directed mutagenesis was then used to systematically delete NHR1 and NHR2 and mutate the PXDLS motif to evaluate the resultant effects on transcriptional regulation, self-renewal, and leukemogenesis imparted by the fusion. A luciferase reporter assay was used to assess transcriptional activation of the BMP2 promoter, a gene which is known to be upregulated by the CBFA2T3-GLIS2 fusion. Loss of NHR1, NHR2, or NHR3 did not alter the ability of the fusion to activate transcription. In contrast, loss of NHR1 and NHR2 in combination (NHR1-2Δ) and mutation of the PXDLS domain decreased transcriptional activation compared to the wild type fusion. The effect of the mutations on self-renewal capability was then evaluated through colony formation assays. Consistent with the luciferase reporter assay, NHR1-2Δ and PXDLS mutants decreased the number of colonies at week six compared to the unmanipulated fusion. Next, we investigated the effect of these mutations on leukemogenesis. Murine models harboring the CBFA2T3-GLIS2 fusion without cooperating mutations have been unsuccessful and patient-derived xenograft models are limited and difficult to manipulate. Therefore, we developed a novel in vivo model of CBFA2T3-GLIS2 driven leukemia. CD34+ stem cells were isolated from human cord blood and transduced with a lentivirus construct encoding the fusion and a GFP reporter. The cells were then differentiated to megakaryoblasts using human TPO and IL1-beta and sorted for purity prior to injection into immunodeficient NSG-SGM3 recipient mice. The fusion positive human primary megakaryoblasts induced a serially transplantable leukemia within 180 days that recapitulates CBFA2T3-GLIS2 positive patient specimens on a transcriptional and protein level. In contrast to our in vitro studies where NHR2 deletion alone did not alter transcriptional activation and self-renewal, the loss of this domain abrogated leukemogenesis in vivo, suggesting a dependency on the association of ETO with the fusion. Mice that received PXDLS mutant cells, however, developed leukemia at a normal latency suggesting that CtBP1 is not required. This study confirms the CBFA2T3-GLIS2 fusion is sufficient for oncogenic transformation of human CD34+ stem cells. We demonstrate that disruption of ETO, p300, and CtBP1 recruitment to the transcriptional complex decreases transcriptional regulation and self-renewal imparted by the fusion. The loss of ETO was the most detrimental to leukemogenesis in our murine model, uncovering a potential new pathway for the development of targeted therapies. Ongoing studies include CUT&RUN sequencing for the fusion, ETO, and CtBP1 to determine co-occupancy of target genes to further understand those that are critical in transformation. DisclosuresGruber: Kura Oncology: Consultancy.

Posttransplant Cyclophosphamide-Based Haploidentical Vs Matched Unrelated Donor Peripheral Blood Hematopoietic Stem Cell Transplantation Using Myeloablative Targeted Busulfan-Based Conditioning for Pediatric Acute Leukemia

Haploidentical related donor (HRD) is a common alternative donor strategy used when matched sibling or unrelated donors are not available for hematopoietic stem cell transplantation (HSCT). Post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis is an attractive option when performing a HRD HSCT because of its promising outcomes and easy application. However, there have been no studies comparing HRD HSCT with PTCy and MUD HSCT with antithymocyte globulin, using similar busulfan-based myeloablative conditioning regimen in pediatric acute leukemia. Herein, we compared the outcomes in children and adolescents with acute leukemia after HRD HSCT with PTCy (n=35) and matched unrelated donor (MUD) HSCT (n=45) after targeted busulfan-based myeloablative conditioning using intensive pharmacokinetic monitoring. The median follow-up times of the HRD and MUD groups were 3.7 and 4.6 years. No engraftment failure was observed. The cumulative incidence of GVHD grades II-IV (34.3% versus 48.9%, p=0.142), grades III-IV (2.9% vs. 8.9%, p=0.272), extensive chronic GVHD (11.4% vs. 18.3%, p=0.417), relapse (25.6% vs. 28.0%, p=0.832), and non-relapse mortality (0% vs. 2.2%, p=0.420) were not significantly different. The 3-year severe chronic GVHD-free/relapse-free, leukemia-free and overall survival rates in the HRD and MUD groups were 62.9±8.7% versus 49.8±7.6% (p=0.318), 74.4±8.0% versus 67.5±7.2% (p=0.585), and 88.6±5.4% versus 83.7±5.7% (p=0.968), respectively. In subgroup analyses of patients with acute lymphoblastic leukemia and acute myeloid leukemia, there were no significant differences in outcomes between the groups. Our results demonstrated that HRD HSCT with PTCy using a targeted busulfan-based myeloablative conditioning shows outcomes similar to those of MUD HSCT. HRD HSCT with PTCy could be considered for pediatric acute leukemia patients who lack an HLA-matched donor. DisclosuresKang: Cartexell: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Korea: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen Korea: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Outcomes for paediatric acute leukaemia patients admitted to the paediatric intensive care unit.

Children with acute leukaemia (AL) are a high-risk population for infections and life-threatening conditions requiring paediatric intensive care unit (PICU) admission, presenting an increased mortality rate. A few literature exists about PICU outcomes in this kind of patients, especially with haematopoietic stem cell transplant (HSCT) background. We investigated the clinical and epidemiological characteristics of these patients as well as their outcomes. A retrospective, single-centre analytical/observational study was conducted from January 2011 to December 2018 in the PICU of a tertiary care hospital. AL patients from 28days to 18years old admitted to the PICU were included, excluding those with histories of HSCT or CAR T-cell therapy. We collected epidemiological and clinical characteristics, laboratory and microbiology results and outcomes. Forty-three patients with AL required urgent admission (35 lymphoblastic and 8 myeloblastic) for 63 different episodes. The main reasons were sepsis (21, 33.3%), hyperleukocytosis (12, 19%), respiratory failure (11, 17.5%) and seizures (8, 12.7%). Nineteen (30.2%) required inotropic support, and fifteen (23.8%) required mechanical ventilation. Three patients died at the hospital (3/43, 6.9%). Sixty-day mortality was 9.3%, and 1-year mortality was 13.9%. There was no differences regarding the type of AL and 60-day mortality (log-rank 2.652, p = 0.103).Conclusion: In our study, the main cause of admission for AL patients was infection, which was associated to more severity and longer hospital admission. What is Known: •Acute leukaemia is the most common childhood cancer. Admission to a paediatric intensive care unit is required in 30% of children with acute leukaemia. •Regarding the outcomes of children with acute leukaemia that require admission to the intensive care unit data are scarce. What is New: • Mortality in acute leukaemia patients admitted to the paediatric intensive care unit is lower than that of patients with a history of stem cell therapy but higher than that of patients with solid tumours. • The main reason for admission was sepsis, which is related in literature to more severity and long length of stay.

Renal Dysfunction in Pediatric Acute Leukemia Patients after Allogeneic Hematopoietic Cell Transplantation with Total Body Irradiation-Containing Conditioning Regimen

<h3>Purpose/Objective(s)</h3> Renal dysfunction after hematopoietic cell transplantation (HCT) is a multi-factorial disorder. Studies have linked dose and fractionation with the incidence of late renal dysfunction in patients who underwent total body irradiation (TBI)-based myeloablative conditioning, but the effect of dose rate remains under studied. We conducted a single-institution retrospective study to elucidate the effect of TBI parameters and peri-HCT factors on late renal dysfunction among pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) after allogeneic HCT. <h3>Materials/Methods</h3> 123 patients (age 1-22) with acute leukemia (38 AML, 85 ALL) underwent HCT using a TBI-based regimen at our institution from 2006-2019. HCT conditioning regimen included cyclophosphamide with or without fludarabine followed by TBI (13.2 Gy in 8 twice-daily fractions over 4 days). TBI dose rate was limited to < 20 cGy/min but ranged from 8.7-19.2 cGy/min depending on Linac availability. TBI parameters and peri-HCT factors were recorded and stratified by recipient of high-dose-rate (HDR; > 15 cGy/min; 35%) or low-dose-rate (LDR; ≤15 cGy/min; 65%) TBI. All patients received a calcineurin inhibitor to prevent graft-versus-host disease (GVHD). Serum creatinine (Cr) was recorded at baseline and trended post-HCT. Late renal dysfunction was defined as persistent increase of Cr > 1.2 mg/dL or ≥ 1.25 times the upper limit of age-dependent normal, onset ≥ 3 months after HCT. Using a statistical software, dichotomous variables were tested using Chi-square or Fisher's exact test; and continuous variables using Wilcoxon rank-sum test. Univariate and multivariate analyses were used to examine the association of these variables with late renal dysfunction. <h3>Results</h3> A total of 14 patients developed late renal dysfunction (11%): 6/38 patients in HDR group (14%) vs. 8/79 patients in LDR group (10%, <i>P</i> = 0.03). Comparison between HDR and LDR groups found no difference in age, sex, remission status, HCT comorbidity index (HCT-CI, predictive of late organ dysfunctions, factoring in baseline Cr) or baseline Cr. More patients in the HDR group were cord blood recipients taking cyclosporine/mycophenolate mofetil (37% vs. 19% in LDR, <i>P</i> < 0.01), and fewer were sibling recipients taking tacrolimus/methotrexate (0% vs. 10%, <i>P</i> < 0.01). More patients in HDR group developed acute GVHD (35% vs. 27%, <i>P</i> = 0.05). In univariate analysis, incidence of late renal dysfunction was associated with patient's age ≤12 at HCT (22% vs. 5% > 12), intermediate-high HCT-CI (22% vs. 6% low HCT-CI) and HDR (24% vs. 8% in LDR). On multivariate regression, late renal dysfunction remained associated with age, HCT-CI, and HDR (<i>P</i> = 0.01, 0.02, and < 0.01 respectively). <h3>Conclusion</h3> Patient's age ≤12 at HCT, intermediate-high HCT-CI, and HDR were associated with late renal dysfunction post-HCT. Since dose rate is the only modifiable factor, adoption of LDR TBI is recommended.