Childhood Acute Leukemia Research Articles

Quantification of deoxythioguanosine in human DNA with LC-MS/MS, a marker for thiopurine therapy optimisation.

In the treatment of diseases such as acute childhood leukaemia (ALL) and inflammatory bowel disease (IBD), the thiopurines azathioprine, 6-mercaptopurine, and 6-thioguanine are used. Thiopurines are antimetabolites and immunomodulators used to maintain remission in patients. They are all prodrugs and must be converted into thecompeting antimetabolites thioguanosine triphosphate and deoxythioguanosine triphosphate for final incorporation into RNA or DNA. The current therapeutic drug monitoring (TDM) method measures the sum of the formed metabolites in the sample, after acidic hydrolysis at high temperature. In this work, the goal is to measure these drugs closer to their pharmacological endpoints, once incorporated into DNA. After extracting DNA from whole blood, followed by DNA hydrolysis, 2'-deoxythioguanosine (dTG) and the complementary natural nucleobase 2'-deoxycytidine (dC) were measured. Chromatographic separation on a HSS T3 column followed by mass spectrometric detection was performed in multi-reaction monitoring (MRM) mode on a Xevo TQ-XS with ESI in positive mode, within 5 min. The concentration range for dTG was 0.04-5 nmol/L, and for dC, 0.1-12.5 µmol/L. The lower limit of detection was determined to a concentration of 0.003 nmol/L for dTG and 0.019 µmol/L for dC. The intra- and inter-assay imprecision for the quality controls ranged between 3.0 and 5.1% and between 8.4 and 10.9%, respectively. Sample stability for up to 4 years is shown. In summary, a sensitive method to quantify the thiopurines incorporated into DNA as dTG has been developed and will be used in further clinical studies for a better understanding of the mode of action of the thiopurines and the use of this method in TDM.

Considerations for using tree-based machine learning to assess causation between demographic and environmental risk factors and health outcomes.

Evaluation of the heterogeneous treatment effect (HTE) allows for the assessment of the causal effect of a therapy or intervention while considering heterogeneity in individual factors within a population. Machine learning (ML) methods have previously been employed for HTE evaluation, addressing the limitations associated with modelling complex systems. In this work, three tree-based ML algorithms, causal random forest (CRF), causal Bayesian additive regression trees (CBART), and causal rule ensemble (CRE), are used to analyze the potential causation of benzene exposure to cause childhood acute myeloid leukemia (AML). Data for this analysis is generated by drawing samples from a previously developed model that estimates AML probability given as input demographic information and benzene exposure. Comparison is drawn between the three tree-based algorithms in terms of the predicted average treatment effect (ATE), the regression coefficient of determination, and the computational time of each algorithm. Minimal difference is reported between the three tree-based algorithms in terms of the ATE, as well as the regression coefficient of determination. However, CRF outperforms CBART in terms of algorithm computational time. Moreover, CRF allows for both continuous and binary treatment variables, as opposed to CBART and CRE, making it better suited to environmental health studies, where exposure levels of pollutants shall be considered continuous. Following the comparison of all three algorithms, the influence of adding Gaussian noise to the treatment and outcome variables, as well as outliers, is investigated using CRF. A set of considerations is drawn to guide researchers in using these algorithms. These considerations detail the simulation settings, applications, and results interpretation and aim to provide prompt information in decision-making surrounding the establishment of pollutant exposure thresholds in environmental risk assessments.

The role of routing in the diagnosis of acute leukemia in children: an observational retrospective non-randomized study

Introduction. Acute leukemia (AL) is the commonest malignancy of childhood. Early diagnosis of AL is difficult due to the non-specificity of primary symptoms, which are often hidden under the "masks" of other diseases. Aim. Assess the delay in diagnosis depending on the areas of residence in the Tver region and area remoteness from the Tver Regional Clinical Children's Hospital. Materials and methods. The analysis included 35 patients hospitalized in the Department of Oncology and hematology of the RCCH for the period from 2018 to 2023. The diagnoses were: ALL - 30 (86%), AML - 3 (9%), and AL of unspecified cell type (ALUCL) - 2 (5%) patients. The mean age was 61 months. Thrombocytopenia and anemia at the time of diagnosis were found in 76% and 78%, respectively. Leukocytosis 20 x 109/L was observed in 58%, leukopenia 3.5 x 109/L in 15% of patients. In 97% of cases blasts (2% to 95%) were detected in peripheral blood. In the city of Tver (group 1) and the Tver region (group 2), 16 (46%) and 19 (54%) patients were identified, respectively. The mean age of patients in group 1 is 28.6 months, and in group 2 - 72.3 months (p = 0.1). Results. In group 1 and 2, ALL was diagnosed in 14 (88%) and 16 (84%), AML in 1 (6%) and 2 (11%) and ALUCL in 1 (6%) and 1 (5%) cases, p = 0.6, 0.7 and 0.95, respectively. Delay of diagnosis in the general group (n = 35) was observed 2 weeks in 21 (60%) cases, 2-4 weeks - in 7 (20%), ≥4 - ≤ 8 weeks - in 4 (11%) and 8 weeks - in 3 (9%) cases. Delayed diagnosis among patients living in the city of Tver and Tver region was observed 2 weeks in 7 (44%) vs. 13 (68%) cases, 2-4 weeks - in 6 (38%) vs 3 (17%), ≥4 - ≤ 8 weeks - in 1 (6%) vs 1 (5%) and 8 weeks - in 2 (12%) vs 2 (10%) cases, respectively (p = 0.37). There was no significant impact of the distance of the residence place from the level 3 children's hospital providing specialized care (RCCH) on the time of diagnosis. Conclusion. The distance from the third-level hospital did not affect the period of diagnosis of AL in children.

Glycated albumin may have a complementary role to glycated hemoglobin in glucose monitoring in childhood acute leukemia.

Glycated hemoglobin (HbA1c) as a glycemic index may have limited value in pediatric patients with acute leukemia as they often present with anemia and/or pancytopenia. To address this issue, we evaluated the usefulness of glycated albumin (GA) as a glycemic monitoring index in pediatric patients with acute leukemia. Medical records of 25 patients with type 2 diabetes mellitus (T2DM), 63 patients with acute leukemia, and 115 healthy children from Seoul St. Mary's Hospital, The Catholic University of Korea, were retrospectively investigated for serum GA, HbA1c, and fasting blood glucose (FBG) levels, along with demographic data. GA, HbA1c, and FBG levels did not differ between the control and acute leukemia groups. In the T2DM group, positive correlations were observed among GA, HbA1c, and FBG (P<0.01). Although GA level was not associated with the HbA1c level in the control group, GA and HbA1c levels showed a positive correlation in the acute leukemia group (P=0.045). Regression analysis revealed GA and HbA1c levels to be positively correlated in the acute leukemia and T2DM groups even after adjusting for age, sex, and body mass index z-score (P=0.007, P<0.01). GA may be a useful complementary parameter to HbA1c for glycemic monitoring in pediatric patients with acute leukemia, similar to its use in patients with T2DM.

Central nervous system complications during treatment in childhood acute leukemia.

Central nervous system (CNS) complications can be seen in patients with leukemia, depending on the disease itself and the chemotherapeutic agents used. This study focused on CNS complications during treatment in children with acute leukemia in a single pediatric institution. CNS complications were evaluated retrospectively in 115 patients with ALL and AML. Patients with CNS leukemia infiltration at the time of diagnosis or during a neurological event, late-onset encephalopathy, peripheral neuropathy, or a previous history of neurological abnormalities were excluded from the study. A total of 115 children's clinical records with acute leukemia over a four-year period were reviewed. Acute CNS complications developed in 23.1% of acute myeloid leukemia (AML) patients and in 13.5% of acute lymphoblastic leukemia (ALL) patients. CNS complications developed most frequently during the induction phase of the treatment (66.7%). Seizures were the most common symptom (9 patients, 50%), followed by hemiparesis (4 patients, 22.2%) and headache (4 patients, 22.2%). Six patients (33.3%) had chemotherapy-induced toxic leukoencephalopathy, two (11.1%) had Wernicke's encephalopathy, and one patient (5.6%) each had sinus vein thrombosis, posterior reversible encephalopathy syndrome, and CNS infection. Sequelae occurred in three patients (16.7%), and only one patient (5.6%) died due to a CNS complication. Awide variety of symptoms can be observed in childhood leukemia, depending on the disease itself, the chemotherapeutic agents used and a lot of other conditions such as nutritional problems. Our research shows that several CNS complications might manifest with similar symptoms; differentiated diagnosis between the underlying etiological reasons can be made by neuroimaging.

Familial Cases of Acute Leukemia in Children in Uzbekistan

Familial Cases of Acute Leukemia in Children in Uzbekistan

Long-Term Outcomes of Childhood Acute Lymphocytic Leukemia Treated with Adapted Berlin-Frankfurt-Münster (BFM) Protocols: A Multicentric Analysis from a Developing Country.

The objective of the current study was to determine the survival probabilities of children and adolescents with acute lymphocytic leukemia treated with adapted Berlin-Frankfurt-Münster (BFM) protocols and compare our results with the original BFM reports. This retrospective study included 695 patients up to 19 years old treated with adapted BFM protocols between 1997 and 2018 in four hospitals in Rio de Janeiro. The 1997-2007 and 2008-2018 cohorts were analyzed separately. More than half of the patients were stratified into the high-risk BFM classification. Overall and event-free survivals were, in the 1997-2007 period, respectively, 88% and 80% (BFM standard risk group-SRG), 75% and 67% (intermediate risk group-IRG), and 48% and 33% (high-risk group-HRG). The corresponding numbers for the 2008-2018 period were 93% and 84% (SRG), 75% and 63% (IRG), and 64% and 57% (HRG). In the second period, both the OS (HR = 0.71, p = 0.011) and EFS (HR = 0.62, p < 0.001) were higher. Except for the intermediate-risk group, the latter results are comparable to the BFM. The BFM protocol adaptations can be safely implemented in developing countries, accounting for local specificities.

Cost-effectiveness of treating childhood acute myeloid leukemia at a tertiary care center in North India.

Childhood cancers are a significant global health concern, particularly in low- and middle-income countries (LMICs), where over 80% of childhood cancer patients reside. In India, acute myeloid leukemia (AML) constitutes a significant portion of childhood cancers; however, the data on the cost-effectiveness of childhood AML treatment in India and other LMICs remain limited. The study focused on children (<15years of age) diagnosed with AML at a tertiary care cancer center in North India. Data, including treatment outcome, treatment-related morbidity, mortality, and costs were retrospectively collected from the electronic medical record and hospital database. Cost-effectiveness was assessed using disability-adjusted life years (DALY) averted in relation to the country-specific cost-effectiveness threshold. Among 59 AML patients, treatment-related high mortality rates, abandonment, and limited access to bone marrow transplantation were notable challenges. Intensive chemotherapy resulted in substantial sepsis-related complications, with treatment-related mortality reaching 30%. The 3-year event-free survival and overall survival of the 43 patients who received intensive therapy were 24.5%±7.6% and 27.9%±8.3%, respectively. Despite these challenges, treating childhood AML was still found to be cost-effective. The total cost per newly diagnosed patient treated with curative intent was $4454. Cost per DALY averted accounted for 24% of the gross domestic product (GDP) per capita, rendering the treatment to be cost-effective with a stringent cost-effectiveness threshold utilized. The study underscores the challenges faced while treating childhood AML in LMICs, including treatment-induced high sepsis-related mortality and abandonment. Despite these challenges, it remains cost-effective to treat childhood AML in India. Future efforts should focus on reducing treatment-related morbidity and mortality to further improve outcomes and cost-effectiveness.

National study reveals gram negative bacteremia on contemporary pediatric AML protocol

Since bacteremia complicates childhood Acute myeloid leukemia (AML) patients, we assessed bacteremia rates in Israeli children with de-novo AML. All chemotherapy courses of patients enrolled in NOPHO-DBH-2012 AML protocol were included. Down syndrome, acute promyelocytic leukemia were excluded. Among 69 patients, seven had focal bacterial infections. Of the remaining 62, 77.4% had 1–8 bacteremias. Of 238 chemotherapy courses, 98 (41.2%) had bacteremia: 66 (67.3%) predominantly Gram-negative rods (GNR); 28 (28.6%) Gram-positive cocci. Escherichia coli; followed by Klebsiella were most common. Older age, Arab ethnicity, and presenting white blood cell count were associated with an increased risk of bacteremia in the univariable analysis, but these associations were not confirmed in the multivariable analysis. Mortality was high (9.7%), and bacteremia increased PICU utilization 7-fold half from GNR. Most isolates were sensitive to vancomycin/meropenem (94.7%), but GNR had low sensitivity to quinolones (61.8%). High mortality and morbidity of de-novo AML patients from predominantly GNR bacteremia require specific interventions but limited susceptibility to quinolones hampers prophylaxis.

Long-term survival outcome of childhood acute myeloid leukemia: a 43-year experience in Thailand, a resource-limited country

Although there have been advances in treating pediatric patients with acute myeloid leukemia (AML) in developed countries, outcomes in low- to middle-income countries remain poor. The goal of this study was to investigate the outcomes in children with AML who were treated at a tertiary care center in Thailand. We divided the study into 4 research periods based on the chemotherapy protocols employed. The 5-year probabilities of event-free survival (pEFS) rates for periods 1–4 were 19.0%, 20.6%, 17.4%, and 37.3% (p value = 0.32), while the 5-year probabilities of overall survival (pOS) rates were 19.0%, 24.7%, 18.7%, and 42.5% (p value = 0.18), respectively. The multivariable model indicated an improvement in 5-year pOS between periods 1 and 4 (p value = 0.04). Age, white blood cell count, and study period were significant predictors of survival outcomes. The pOS of AML patients improved over time, increasing from 19.0% to 42.5%.

Current situation and prospect of diagnosis and therapy of childhood acute leukemia in China

Acute leukemia is the most common hematopoietic stem cell malignant tumor in children, which ranks in the top one of the incidence of tumor in children, it is a major disease that affects the growth and survival of children. With the continuous improvement of medical diagnosis and treatment and the extensive development of immunotherapy, the survival rate and quality of life of children with acute leukemia have been significantly improved. In recent years, three cooperative groups of childhood leukemia have been established in China, and a series of high-level research results have been published. In the future, efforts should be made to promote the process of standardization and homogenization in the diagnosis and treatment of children's acute leukemia, explore the monitoring targets of sensitive residual diseases, and find the best treatment for refractory/recurrent cases. Speeding up the clinical research of new drugs will be an urgent problem and development direction in the field of acute leukemia diagnosis and treatment in children.

Review of Leukemia in Children

Leukemia is the most common cancer in children, accounting for approximately one-third of all pediatric cancers. This disease affects the blood-forming tissues, with leukemic cells first growing in the bone marrow, then entering the peripheral blood, and possibly spreading to various organs, including the skin. Acute leukemia’s clinical symptoms stem from the frequently rapid onset of bone marrow failure. The clinical presentation typically includes high fever, gastrointestinal and pulmonary symptoms, severe and worsening anorexia, muscle and joint pain, and bleeding. This review explores the incidence and general epidemiology of childhood leukemia, including risk-increasing syndromes; recognizes the clinical presentation and interpretation of blood counts; examines potential oncologic emergencies; describes prognostic factors and the importance of minimal residual disease in precursor B-lymphoblastic leukemia; highlights supportive care in treating acute myelogenous leukemia; and addresses long-term complications of modern childhood leukemia treatments. This narrative review discusses the evidence suggesting an in-utero origin of childhood acute leukemia, focusing on acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). It highlights the significant diagnostic presence of these acute leukemias among hematologic cancers, the investigations into prenatal leukemogenesis, and the literature on prenatal risk factors during gestation.

Review of Leukemia in Children

Leukemia is the most common cancer in children, accounting for approximately one-third of all pediatric cancers. This disease affects the blood-forming tissues, with leukemic cells first growing in the bone marrow, then entering the peripheral blood, and possibly spreading to various organs, including the skin. Acute leukemia’s clinical symptoms stem from the frequently rapid onset of bone marrow failure. The clinical presentation typically includes high fever, gastrointestinal and pulmonary symptoms, severe and worsening anorexia, muscle and joint pain, and bleeding. This review explores the incidence and general epidemiology of childhood leukemia, including risk-increasing syndromes; recognizes the clinical presentation and interpretation of blood counts; examines potential oncologic emergencies; describes prognostic factors and the importance of minimal residual disease in precursor B-lymphoblastic leukemia; highlights supportive care in treating acute myelogenous leukemia; and addresses long-term complications of modern childhood leukemia treatments. This narrative review discusses the evidence suggesting an in-utero origin of childhood acute leukemia, focusing on acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). It highlights the significant diagnostic presence of these acute leukemias among hematologic cancers, the investigations into prenatal leukemogenesis, and the literature on prenatal risk factors during gestation.

Diagnosis of acute leukemia in children: the impact of remote residence on the time to make a diagnosis

Background. Acute leukemia (AL) is the most common childhood cancer with an incidence rate of about 55–62 cases per 1 million children under 18 years of age. Acute leukemia is difficult to diagnose due to nonspecific symptoms, which are often hidden under the “masks” of other diseases. This problem is especially relevant for regions with a population of up to 100,000 people, where AL in children is diagnosed once every 2–5 years causing too low cancer alertness among pediatricians. Aim: to assess the delay in diagnosis depending on the areas of residence in the Tver region and area remoteness from the Tver Regional Clinical Children’s Hospital (RCC H). Material and Methods. The analysis included 35 patients hospitalized in the Department of Oncology and Hematology of the RCC H for the period from 2018 to 2023. The diagnoses were: ALL, C91.0 – 30 (86 %), AML , C92 – 3 (9 %), and AL of unspecified cell type (ALUCL ), C95.0 – 2 (5 %) patients. The mean age was 61 months. Thrombocytopenia and anemia at the time of diagnosis were found in 76 % and 78 %, respectively. Leukocytosis &gt;20×109/L was observed in 58 %, leukopenia &lt;3.5×109/L in 15 % of patients. In 97 % of cases, blasts (2 % to 95 %) were detected in peripheral blood. In the city of Tver (group 1) and the Tver region (group 2), 16 (46 %) and 19 (54 %) patients were identified, respectively. The mean age of patients in group 1 was 28.6 months and the mean age in group 2 was 72.3 months (p=0.1). Results. In group 1 and 2, ALL was diagnosed in 14 (88 %) and 16 (84 %), AML in 1 (6 %) and 2 (11 %) and ALUCL in 1 (6 %) and 1 (5 %) cases, p=0.6, 0.7 and 0.95, respectively. Delay in diagnosis in the general group (n=35) was observed &lt;2 weeks in 21 (60 %) cases, 2–4 weeks – in 7 (20 %), ≥4–≤8 weeks – in 4 (11 %) and &gt;8 weeks – in 3 (9 %) cases. Delayed diagnosis among patients living in the city of Tver and Tver region was observed &lt;2 weeks in 7 (44 %) vs 13 (68 %) cases, 2–4 weeks – in 6 (38 %) vs 3 (17 %), ≥4–≤8 weeks – in 1 (6 %) vs 1 (5 %) and &gt;8 weeks – in 2 (12 %) vs 2 (10 %) cases, respectively (p=0.37). There was no significant impact of the distance of the residence place from the level 3 children’s hospital providing specialized care (RCC H) on the time of diagnosis. With the removal of &lt;50 km the diagnosis delay &lt;2 weeks, 2–4 weeks, ≥4–≤8 weeks, &gt;8 weeks was observed in 36, 36, 21 and 7 %, respectively. With the removal of ≥50–≤100 km, the diagnosis was made in the period of 2–4 weeks in 100 % of cases. With the removal of &gt;100 km the diagnosis delay &lt;2 weeks, 2–4 weeks, ≥4–≤8 weeks, &gt;8 weeks was observed in 30, 30, 20 and 20 %, respectively (p=0.78). Conclusion. The distance from the third-level hospital did not affect the period of diagnosis of AL in children, which is achieved by holding daily on-line conferences with country hospitals and out-patient departments followed by the rapid hospitalization of children with suspected oncohematological disorders in the specialized department.

Clinicohematological profile and immunophenotypic patterns of childhood acute leukemia: Prognostic correlation

Acute leukemia (AL) presents a heterogeneous molecular profile, requiring precise diagnostic categorization and subcategorization. The present study aims to estimate the clinicohematological profile and immunophenotypic pattern of childhood AL while conducting prognostic assessments. This cross-sectional study analyzed a total of 68 samples of AL collected from January 2019 to June 2021. The male-to-female ratio was 4.6:1, with a mean age of 6.6 &amp;plusmn; 3.4 years. Total leukocyte count (TLC) was significantly increased in all types of AL (P = 0.03). The median value (interquartile range) of TLC (&amp;times;106/dL) was 8,450 (4,100 &amp;ndash; 27,950), with blast counts in peripheral smears at 59 (24 &amp;ndash; 80), and in bone marrow aspirates (BMAs) at 95 (75 &amp;ndash; 98). There was a significant association (P &lt; 0.001) and a strong association (C = 0.9110) between the morphology of BMA with immunophenotype. Based on immunophenotype, AL was categorized into four groups: B-cell acute lymphoblastic leukemia (B-ALL) (51.5%), T-cell acute lymphoblastic leukemia (T-ALL) (10.3%), AML (22%), and mixed phenotype AL (MPAL) (16.2%). Furthermore, eight subgroups were identified: B lineage, Ia-Common-B-ALL (88.6%) and Ib-Pre-B-ALL (11.4%); T-lineage, IIa-Cortical T-ALL (71.4%) and IIb-Pre-T-ALL (28.6%); AML subgroups, IIIa-M2 (73.93%) and III-M4 (26.7%); and MPAL subgroups, IVa-aberrant expression of myeloid antigens in B-ALL (90.9%), and IVb-aberrant expression of lymphoid markers in AML (9.1%). A poor prognostic immunophenotype (T-ALL, AML) was significantly (P = 0.023) more prevalent in deceased patients with AL. The highest mortality rate was observed in AML (86.4%), followed by T-ALL (57.2%). The most common immunophenotype observed was Common-B-ALL in childhood AL, and a poor prognostic immunophenotype (T-ALL and AML) with the highest mortality rate was found in AML. Thus, knowledge about clinicohematological and immunophenotypic patterns will aid in patient management.

Identification of a novel MEF2C::SS18L1 fusion in childhood acute B-lymphoblastic leukemia

PurposeLeukemia-associated fusion genes are closely related to the occurrence, development, diagnosis, and treatment of leukemia. DNA microarrays and second-generation sequencing have discovered multiple B-ALL fusion genes. We identified a novel MEF2C::SS18L1 fusion gene in a child diagnosed with B-ALL. This study investigates the oncogenicity and prognosis of this fusion gene in B-ALL.MethodsA child with B-ALL who has a MEF2C::SS18L1 fusion is reported as a newly discovered case. Compared the breakpoints, structural domains, clinical phenotypes, and differential expression genes of MEF2C::SS18L1 and MEF2D::SS18.Using “ONCOFUSE” software, the carcinogenicity of MEF2C::SS18L1 is predicted. Using whole transcriptome sequencing, we analyze the breakpoints and the secondary structure of the fusion protein. Further, we compared the structures, differentially expressed genes, and clinical phenotypes of MEF2D and MEF2C fusion genes by DESeq, GO functional enrichment, and flow cytometry immunophenotyping analysis.ResultsWhole transcriptome sequencing identified a MEF2C::SS18L1 fusion transcript in a 3-year-old child with B-ALL. The MADS box, MEF structural domain, HJURP_C structural domain, and TAD I structural domain of MEF2C, and the QPGY structural domain of SS18L1, make up the fusion protein. “Oncofuse” found a 0.99 Bayesian probability that the fusion gene drives cancer. The breakpoint positions, fusion protein secondary structures, differentially expressed genes, and clinical characteristics of this patient were identical to those with MEF2D::SS18 fusion gene.ConclusionWe identified a novel MEF2C::SS18L1 fusion gene in childhood ALL, which shares similar structural and clinical characteristics with MEF2D::SS18. Further studies with more samples should be conducted in future.

Chimeric antigen receptor T-cell therapy in childhood acute myeloid leukemia: how far are we from a clinical application?

Recurrent and/or refractory (R/R) pediatric acute myeloid leukemia (AML) remains a recalcitrant disease with poor outcomes. Cell therapy with genetically modified immune effector cells holds the promise to improve outcomes for R/R AML since it relies on cytotoxic mechanisms that are distinct from chemotherapeutic agents. While T cells expressing chimeric antigen receptors (CAR T cells) showed significant anti-AML activity in preclinical models, early phase clinical studies have demonstrated limited activity, irrespective of the targeted AML antigen. Lack of efficacy is most likely multifactorial, including: (i) a limited array of AML-specific targets and target antigen heterogeneity; (ii) the aggressive nature of R/R AML and heavy pretreatment of patients; (iii) T-cell product manufacturing, and (iv) limited expansion and persistence of the CAR T cells, which is in part driven by the immunosuppressive AML microenvironment. Here we review the results of early phase clinical studies with AML-specific CAR T cells, and avenues investigators are exploring to improve their effector function.

Racial disparities in pediatric patients with acute myeloid leukemia.

10031 Background: Leukemia is a cancer of the blood and bone marrow characterized by the rapid and uncontrolled production of abnormal white blood cells. Acute myeloid leukemia (AML) makes up 15–20% of all childhood acute leukemias (1). The purpose of this study is to use the National Cancer Database (NCDB) to provide an updated investigation of racial disparities in survival in pediatric patients with AML. Investigating the different factors associated with poor outcomes provides valuable information when allocating resources and understanding where policies will be useful to improve patient outcomes. Methods: Pediatric (0-19 years old) AML patients were identified in this retrospective cohort study via the 2004-2020 NCDB. Chi square analysis, Fischer's exact test, and t-tests were used to analyze demographic variables. Kaplan Meier survival analysis was used to compare mean survival across race categories which was repeated with demographic variables of interest using a multivariate Cox regression. Results: A total of 4765 patients were identified in this study. Most patients were male (53.5%), White (73.0%), held private insurance (52.3%), and resided in metropolitan areas (82.0%). The mean age at diagnosis was 8.1 years old. There was no significant difference in age at diagnosis and time to treatment start across racial categories. Black patients had lower mean survival compared to White patients (131 vs 148 months, p&lt;0.001). When controlling for age, sex, metropolitan status, comorbidity status, income, education, and insurance status as covariates, Black race independently portended a poorer prognosis compared to White race (hazard ratio: 1.174, 95% confidence interval: 1.003-1.376, p=0.046). Black patients were more likely to be uninsured (4.1%) compared to White patients (2.8%) (p&lt;0.001). Black patients were more likely to reside in zip codes with lower incomes (36.0% vs 17.6%, p&lt;0.001) and lower education attainment (38.7% vs 27.8%, p&lt;0.001) compared to White patients. Black patients were more likely to have comorbidities with a Charlson-Deyo score of &gt;1 than White patients (11.2% vs 6.2%, p&lt;0.001). Black patients were also more likely to be from metropolitan areas than White patients (90.5% compared to 83.9%, p&lt;0.001). Conclusions: This study indicates that Black AML patients experience lower survival rates and are subject to more predictors of poor outcomes. Black patients were more likely to be uninsured, have comorbidities, live in zip codes with lower incomes and lower education attainment. 1. Morais, R. V. de et al (2021). J De Pediatria, 97(2), 204–210. https://doi.org/10.1016/j.jped.2020.02.003.

Health-related quality of life in children with childhood acute myeloid leukemia in China: A five-year prospective study

PurposeThis study aims to identify the key factors influencing health-related quality of life (HRQoL) of pediatric acute myeloid leukemia (AML) patients following their initial diagnosis and examine their impact on the five-year survival prognosis. MethodsA chart review and follow-up were conducted for children with AML who participated in a prospective cohort study between 2017 and 2020. We identified factors influencing HRQoL through Pediatric Quality of Life Inventory™ (PedsQL™ 4.0), PedsQL™ Cancer Module 3.0 (CM 3.0) and PedsQL™ Family Impact Module 2.0 (FIM 2.0), as well as assessed the impact of impaired HRQoL on the overall outcomes of patients. ResultsSixty-four subjects enrolled in the study had complete HRQoL outcome data, and 61 of them completed the 5-year follow-up. In CM 3.0, age was positively associated with parental proxy reports (p = 0.040), whereas divorced families were negatively associated with child self-reports (p = 0.045). A positive medical history correlates with FIM 2.0 (p = 0.025). Residence (p = 0.046), the occupation of caregivers (p = 0.014), disease severity (p = 0.024), and the only child (p = 0.029) exhibited statistically significant associations with the impairment of HRQoL. Impaired HRQoL scores shown by the PedsQL™4.0 parent proxy report (p = 0.013) and FIM 2.0 (p = 0.011) were associated with a reduced 5-year survival rate. ConclusionsThis study demonstrated that early impairment of HRQoL in pediatric acute myeloid leukemia patients has predictive value for long-term prognosis. Once validated, these findings may provide some guidance to clinicians treating children with AML.

The outcome of relapsed childhood acute lymphoblastic leukemia after allogeneic hematopoietic stem-cell transplantations: A single-center experience.

In children with high-risk childhood acute leukemia who undergo allogeneic hematopoietic stem-cell transplantation (allo-HSCT), relapse is still the leading cause of treatment failure. The prognosis is poor, yet prospective studies have only limited data on risk factors and outcomes. We aimed to understand the outcomes and prognostic factors for patients with acute lymphoblastic leukemia (ALL) who relapsed following allo-HSCT. We analyzed retrospectively 46 children with childhood acute lymphoblastic leukemia who had relapsed after receiving their first alloHSCT. All these patients received salvage chemotherapy which consisted of fludarabine, cytarabine, and idarubicin before performing a second alloHSCT. The median follow-up of the 46 patients after the first transplantation was 366 days. The median time from first allo-HSCT to relapse was 278.4±238.4 days. Forty-six patients received salvage chemotherapy before the second alloHSCT, and CR was achieved in 32 of 46 patients. However, only 17 (37%) of 46 patients received a second allo-HSCT, and 15 of 46 patients died from disease progression, infections, and bleeding. Twelve patients are still alive after the second allo-HSCT. Two-year overall survival (OS) was 38.9%. Local therapy was given to 10 (21.8%) patients, either as part of systemic therapy or alone. In multivariate analyses, the time of relapse and curative salvage therapy with a second allo-HSCT were identified as significant prognostic factors for OS. Children with leukemia who had relapsed after the first allo-HSCT received salvage chemotherapy. Our statistical analysis showed that the second HSCT could be beneficial for outcomes if patients relapsed beyond 180 days of the first allo-HSCT.