Acute Lymphoblastic Leukemia Patients Research Articles

Hierarchical DNA Octahedral Nanoplatform for in Situ Biosensing and Clinical Monitoring of Acute Lymphoblastic Leukemia.

Developing nanoscale platforms with high integration, assembly efficiency, and structural stability for performing complex computations in specific cells remains a significant challenge. To address this, the Three-dimensional Hierarchical Octahedral Robotic (THOR) DNA nanoplatform is introduced, which integrates targeting, logic computation, and sensing modules within a single framework. This nanoplatform specifically binds to cancer cell surface proteins, releasing aptamer-linked fuel chains to initiate subsequent computational processes. Three logic gates efficiently compute any arbitrary binary combination of target proteins. The sensing module employs catalytic hairpin assembly for detecting specific miRNAs with high sensitivity. THOR demonstrates robust functionality both in vitro and in situ. As a proof-of-concept, this nanoplatform to distinguish acute lymphoblastic leukemia (ALL) patients from other leukemia subtypes and healthy participants, achieving 100% accuracy is applied. Additionally, this approach reliably monitored the therapeutic progress of ALL patients, showing strong concordance with bone marrow smear results. The THOR platform highlights the feasibility of constructing a reliable, hierarchical, and multifunctional analytical system based on a single DNA polyhedron. It offers a promising auxiliary tool for clinical diagnostics and therapeutic monitoring.

Effects of oral Lcarnitine supplementation on liver enzymes in pediatric acute lymphoblastic leukemia patients in the maintenance phase of treatment: a randomized clinical trial study

Effects of oral Lcarnitine supplementation on liver enzymes in pediatric acute lymphoblastic leukemia patients in the maintenance phase of treatment: a randomized clinical trial study

Delay in treatment for childhood Acute Lymphoblastic Leukemia at the University of Gondar Comprehensive Specialized Hospital, Northwestern Ethiopia

Background: Despite the critical importance of early blood cancer diagnosis in children for timely treatment, late presentation, delayed diagnosis, and delayed treatment initiation remain significant issues in developing countries, including Ethiopia. Addressing these delays requires improving healthcare infrastructure, public awareness, provider training, and reducing financial barriers. This study aimed to assess referral delays, diagnostic delays, and overall treatment delays among children with acute lymphoblastic leukemia at the University of Gondar Comprehensive Specialized Hospital. Methods: A facility-based cross-sectional study was conducted among pediatric acute lymphoblastic leukemia (ALL) patients under 18 years. Data were collected using a structured questionnaire administered to primary caregivers from December 29, 2022, to January 30, 2024. During the study, 90 ALL cases were included using a consecutive sampling technique. Data were entered and analyzed using SPSS version 25 software, with results presented through descriptive statistics, including frequencies, percentages, graphs, and tables. Binary logistic regression examined associations between sociodemographic factors and treatment delays among childhood ALL patients. Results: A total of 90 children participated, 63 (70.0%) male. Median time from first symptoms to medical consultation was 9.7 days, referral delay 51.3 days, diagnosis delay 3.2 days, and treatment initiation delay 4.6 days. Total delay to treatment was 69 days, with induction mortality at 22%. High-risk ALL, malaria, and delays of 30–90 days increased induction mortality risk. Conclusion: The study revealed significant delays in childhood ALL treatment, contributing to high mortality rates. Timely diagnosis and treatment initiation are critical, particularly for high-risk patients and those with malaria. Strengthening healthcare infrastructure, awareness, and provider training is vital to improve outcomes.

The effects of bone marrow humoral components of B-cell acute lymphoblastic leukemia patients on natural killer cell suppression.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common form of cancer diagnosed in children. While the majority of patients survive with conventional treatment, chemotherapeutic agents have adverse effects and the potential for relapse persists even after full recovery. Given their pivotal function in anti-cancer immunity, there has been a surge in research exploring the potential of natural killer (NK) cells in immunotherapy, which has emerged as a promising avenue for treating leukemia. Nevertheless, the efficacy of NK cell immunotherapy is less pronounced than expected, which suggests the external conditions that affect NK cell functions after the administration to patients with leukemia. In this study, the effects of humoral components in the bone marrow humoral components of B-ALL patients on healthy NK cells were investigated. Healthy peripheral blood mononuclear cells were cultured with and without bone marrow-derived plasma samples of B-ALL patients. The expression of PD-1 and IL-10 were found to be increased whereas the proliferative capacities of NK cells were found to be decreased at the presence of B-ALL plasma samples. Moreover, high IL-10 versus low IL-18 levels were detected in bone marrow plasma samples of B-ALL patients. These findings indicate that humoral components in the bone marrow of B-ALL patients exert a suppressive effect on NK cell functions.

A Unique Case of Extramedullary Relapse in Acute Lymphoblastic Leukemia: Testicular to Ocular, Cardiac, and Colonic Involvement and the Role of Sperm Phenotyping in Diagnosis-Case Report and Literature Review.

Acute lymphoblastic leukemia (ALL) is a malignant condition of lymphoid progenitor cells that primarily affects the pediatric population, but also adults. The 5-year survival rate is 90% in children and approximately 40% in adults, with survival increasing through the use of peripheral stem cell allotransplantation (SCT). The relapse rate after stem cell transplantation (SCT) in adult acute lymphoblastic leukemia (ALL) patients ranges from 35% to 45%, making relapse a major cause of death in this population. Background: We present an atypical case of late testicular involvement in ALL in a 50-year-old man diagnosed with ALL pro-T in remission post-chemotherapy (GMALL 2003 protocol) and allogeneic stem cell transplantation (alloSCT) from a related donor. Methods: This case describes a 50-year-old male with ALL pro-T who experienced three rare extramedullary relapses post-chemotherapy and alloSCT. Five years after remission, he had a unilateral testicular relapse confirmed by immunophenotyping of spermatic fluid. Results: Despite no bone marrow involvement, he was treated with chemotherapy, intrathecal therapy, and bilateral testicular radiotherapy. He later relapsed in the orbit, controlled by radiotherapy, followed by a third relapse in the heart and colon. Conclusions: This case highlights the unusual sites and consecutive nature of extramedullary relapses in adult ALL.

Tyrosine kinase inhibitor discontinuation in non-allografted Philadelphia-positive acute lymphoblastic leukemia patients: a Campus ALL real-life study.

Not available.

Asciminib resistance of a new BCR::ABL1 p.I293_K294insSSLRD mutant detected in a Ph + ALL patient.

Chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia patients largely benefit from an expanding tyrosine kinase inhibitors (TKIs) toolbox that has improved the outcome of both diseases. However, TKI success is continuously challenged by mutation-driven acquired resistance and therefore, close monitoring of clonal genetic diversity is necessary to ensure proper clinical management and adequate response to treatment. Here, we report the case of a ponatinib-resistant Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patient harboring a BCR::ABL1 p.I293_K294insSLLRD mutation. Using in vitro proliferation assays on newly generated Ba/F3 cell lines, we confirmed that the mutation confers moderate resistance to ponatinib, and to imatinib and nilotinib. In contrast, BCR::ABL1SLLRD Ba/F3 cells remain highly sensitive to dasatinib. Unexpectedly, the insertion also provides resistance to asciminib with no inhibitory effect up to 1000nM. Based on predicted structural models, we speculate that the p.I293_K294insSLLRD disrupts the interaction between the SH3 domain and the kinase domain, shifting the equilibrium toward the active conformation. This shift confers resistance to TKIs that preferentially bind to the inactive conformation, as well as to the allosteric asciminib inhibitor. However, the mutation retains sensitivity to dasatinib, which targets the active form of the kinase.

Drug-Induced Cauda Equina Syndrome in an 8-Year-Old Boy With Acute Lymphoblastic Leukemia: An Uncommon Case Report.

Intrathecal methotrexate can cause cauda equina syndrome in pediatric ALL patients, as demonstrated in this rare case of an 8-year-old boy. Symptoms included progressive limb weakness and urinary retention. Early recognition, prompt discontinuation of the offending agent, and multidisciplinary management are crucial. Vigilant neurological monitoring is essential for pediatric acute lymphoblastic leukemia patients receiving intrathecal chemotherapy.

Total body irradiation-based myeloablative conditioning for acute lymphoblastic leukaemia patients undergoing allogeneic haematopoietic stem cell transplantation: the best way to prevent relapse in a real-world scenario.

Total body irradiation-based myeloablative conditioning for acute lymphoblastic leukaemia patients undergoing allogeneic haematopoietic stem cell transplantation: the best way to prevent relapse in a real-world scenario.

Prognostic and therapeutic implications of measurable residual disease levels during remission induction of childhood ALL.

We evaluated the prognostic and therapeutic significance of measurable residual disease (MRD) during remission induction in pediatric acute lymphoblastic leukemia (ALL) patients. In the CCCG-ALL-2015 protocol, 7640 patients were categorized into low-, intermediate-, or high-risk groups based on clinical and genetic features. Final risk classification was determined by MRD assessed via flow cytometry on Days 19 and 46 of remission induction, with additional intensified chemotherapy for Day 19 MRD ≥1%. B-ALL patients with negative MRD (<0.01%) on Day 19 or Day 46 had significantly better 5-year event-free survival (EFS) than those with MRD 0.01-0.99%, who in turn had better EFS than patients with MRD ≥1%. Provisional low-risk patients with Day 19 MRD ≥1% but negative Day 46 MRD, reclassified as intermediate-risk, had comparable 5-year EFS to low-risk patients with Day 19 MRD 0.3-0.99% and negative Day 46 MRD (82.5% vs. 83.0%) and better EFS than provisional low-risk patients with MRD on both days (83.0% vs. 72.6%, P<0.001). Similarly, provisional intermediate-risk B-ALL patients with Day 19 MRD ≥1% but negative Day 46 MRD, who received additional therapy, had better 5-year EFS compared to those with Day 19 MRD between 0.3-0.99% (70.7% vs. 53.0%, P<0.001). Among low-risk patients with negative Day 46 MRD, those with negative Day 19 MRD had superior EFS compared to those with positive Day 19 MRD (91.7% vs. 86.1%, P<0.001). Optimal use of Day 19 MRD could improve individualized treatment and outcomes. Chinese Clinical Trial Registry (ChiCTR-IPR-14005706).

Hypersensitive reactions to platelet transfusion: A case report of urticarial hives and pre-septal cellulitis in the context of a patient with Pre-B acute lymphoblastic leukaemia patient

Hypersensitive reactions to platelet transfusion: A case report of urticarial hives and pre-septal cellulitis in the context of a patient with Pre-B acute lymphoblastic leukaemia patient

The Gene Expression Levels of ETS2, ADAM28, and GPRC5D Genes in Acute Lymphoblastic Leukemia Patients

Background: Genetic biomarkers significantly influence the pathological differentiation and proliferation of lymphoid precursor cells, contributing to the development of Acute Lymphoblastic Leukemia (ALL) in children. This case-control study aimed to assess the expression levels of three potential biomarkers: ETS2, ADAM28, and GPRC5D, in patients with ALL. Materials and Methods: In this cross-sectional study, a group of ALL patients (n=65) referred to the hematology-oncology departments of Nemazee Hospital and Amir Hospital in Shiraz, Iran, from May 2018 to May 2021 were selected as the patient group. A control group (n=65) of age- and gender-matched volunteers was also selected. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to study the expression profiles of these genes in patients and compare the results to those of a control group. The study included 65 patients with ALL and 65 healthy participants. The Pfaffl method of relative quantification, which compares the threshold cycle of a constitutive gene (TBP) with the test gene of each sample in duplicate, was used to determine the relative levels of ETS2, ADAM28, and GPRC5D gene expression. SPSS software version 16 was used for statistical analysis. Nonparametric tests were used to analyze non-normally distributed data, and the Mann-Whitney test was used to compare the medians and ranges and a p-value of 0.05 was considered significant. Results: The patient group showed significantly greater expression of the ETS2 and ADAM28 genes compared to the control group. (P &lt;0.0001; fold changes of 2.80 and 2.14, respectively), while GPRC5D expression remained unchanged (P &gt;0.05). Conclusion: These genetic biomarkers in patients with ALL may play an oncogenic role in the pathogenesis of the disease and could serve as potential novel biomarkers for ALL.

Clearing MRD positivity with blinatumomab in pediatric B-cell acute lymphoblastic leukemia: insights from droplet digital PCR and flow cytometry.

Blinatumomab has shown to improve survival outcomes in B-cell acute lymphoblastic leukemia (B-ALL) patients with measurable residual disease (MRD) detected by multiparametric flow cytometry (MFC). However, data on blinatumomab clearing MRD with high sensitivity remain scarce. This study evaluates the effectiveness of blinatumomab in eradicating low levels of MRD, as detected by droplet digital PCR (ddPCR) but undetectable by MFC, in children with B-ALL. Patients (n = 9) whose MRD was undetectable by MFC but detectable by ddPCR after chemotherapy and followed by blinatumomab consolidation were included retrospectively. After the administration of blinatumomab, 5 out of 9 patients (55.56%) successfully achieved undetectable levels of ddPCR-MRD. Notably, among the 4 patients with BCR::ABL1 gene-positive acute lymphoblastic leukemia (ALL), only one achieved gene negativity. Starting from the initiation of blinatumomab treatment, with a median follow-up of 12 months, all patients remained in complete remission. Our study was the first to demonstrate that blinatumomab could further eradicate ddPCR MRD after patients achieve MFC-MRD undetectable status in B-ALL patients.

Five-year outcomes of CD19 followed by CD22 chimeric antigen receptor T-cell therapy in B-cell acute lymphoblastic leukemia patients who relapsed after allo-transplantation.

Not available.

Screening JAK2 V617F Mutation in Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) Patients

Screening JAK2 V617F Mutation in Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) Patients

A regression based approach to phylogenetic reconstruction from multi-sample bulk DNA sequencing of tumors.

DNA sequencing of multiple bulk samples from a tumor provides the opportunity to investigate tumor heterogeneity and reconstruct a phylogeny of a patient's cancer. However, since bulk DNA sequencing of tumor tissue measures thousands of cells from a heterogeneous mixture of distinct sub-populations, accurate reconstruction of the tumor phylogeny requires simultaneous deconvolution of cancer clones and inference of ancestral relationships, leading to a challenging computational problem. Many existing methods for phylogenetic reconstruction from bulk sequencing data do not scale to large datasets, such as recent datasets containing upwards of ninety samples with dozens of distinct sub-populations. We develop an approach to reconstruct phylogenetic trees from multi-sample bulk DNA sequencing data by separating the reconstruction problem into two parts: a structured regression problem for a fixed tree [Formula: see text], and an optimization over tree space. We derive an algorithm for the regression sub-problem by exploiting the unique, combinatorial structure of the matrices appearing within the problem. This algorithm has both asymptotic and empirical improvements over linear programming (LP) approaches to the problem. Using our algorithm for this regression sub-problem, we develop fastBE, a simple method for phylogenetic inference from multi-sample bulk DNA sequencing data. We demonstrate on simulated data with hundreds of samples and upwards of a thousand distinct sub-populations that fastBE outperforms existing approaches in terms of reconstruction accuracy, sample efficiency, and runtime. Owing to its scalability, fastBE enables both phylogenetic reconstruction directly from indvidual mutations without requiring the clustering of mutations into clones, as well as a new phylogeny constrained mutation clustering algorithm. On real data from fourteen B-progenitor acute lymphoblastic leukemia patients, fastBE infers mutation phylogenies with fewer violations of a widely used evolutionary constraint and better agreement to the observed mutational frequencies. Using our phylogeny constrained mutation clustering algorithm, we also find mutation clusters with lower distortion compared to state-of-the-art approaches. Finally, we show that on two patient-derived colorectal cancer models, fastBE infers mutation phylogenies with less violation of a widely used evolutionary constraint compared to existing methods.

Role of Glutaredoxin-1 and some Oxidative Stress Enzymes in Acute Lymphocytic Leukemia Patients

Role of Glutaredoxin-1 and some Oxidative Stress Enzymes in Acute Lymphocytic Leukemia Patients

Efficacy and safety of olverembatinib in adult BCR::ABL1-positive ALL with T315I mutation or relapsed/refractory disease.

Third-generation tyrosine kinase inhibitors (TKIs) have much potential for the treatment of BCR::ABL1-positive leukaemia, particularly that harbouring the ABL1 T315I mutation. Olverembatinib (HQP1351), a novel third-generation TKI, has favourable efficacy and safety profiles in chronic myeloid leukaemia. Here, we present the clinical findings from 31 BCR::ABL1-positive acute lymphoblastic leukaemia (ALL) patients who received olverembatinib. Among the 14 patients with overt relapsed/refractory (R/R) disease (including 10 with the T315I mutation), 71.4% achieved an overall response. Of the other 17 patients with minimal residual disease (MRD)-positive ALL (including 14 with the T315I mutation), 60.0% and 47.1% achieved MRD flow negativity and complete molecular remission, respectively. With a median follow-up time of 16.3 months, the median event-free survival and overall survival were 3.9 and 8.3 months respectively, in overt R/R patients, and 11.5 and 18.4 months in MRD-positive patients. Allogeneic haematopoietic stem cell transplantation further improved outcomes among responders. The safety profile was generally manageable. This study suggests that olverembatinib-based therapy is another promising option for BCR::ABL1-positive ALL in addition to ponatinib, especially for patients with MRD-positive disease and a single T315I mutation.

Copy number alterations in pediatric B-cell precursor acute lymphoblastic leukemia patients and their association with patients' outcome.

Genetic abnormalities provide diagnostic and prognostic information for pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. The aim of this study was to determine the effects of genetic CNAs and RUNX1 gene abnormalities on the outcome of pediatric BCP-ALL patients. This study included 78 de novo-BCP-ALL pediatric patients who presented to the Pediatric Oncology Department of the National Cancer Institute (NCI), Cairo University. We aimed to study the impact of copy number alteration (CNA) of 8 of the most altered genes in BCP-ALL patients, in addition to RUNX1 gene abnormalities, on patient survival and response to treatment. Multiplex ligation-dependent probe amplification (MLPA) was used to detect CNA, while RUNX1 gene alterations were detected by fluorescence in situ hybridization (FISH). CNA of the PAX5 gene was significantly associated with worse overall survival (OS) and event-free survival (EFS) (P = 0.012 and P = 0.025, respectively). An increase in the CNA of ETV6 was associated with an increase in minimal residual disease (MRD) on day 15 (P = 0.041). Although RUNX1 gene abnormalities were not a predictor of shorter OS or EFS, an interesting significant association was found between PAX5 CNA and RUNX1 gene gain and translocation (P = 0.017 and P = 0.041, respectively). PAX5 CNA is an adverse prognostic factor. ETV6 CNA is associated with high MRD on day 15.

Machine learning evaluation of intensified conditioning on haematopoietic stem cell transplantation in adult acute lymphoblastic leukemia patients

BackgroundThe advantage of intensified myeloablative conditioning (MAC) over standard MAC has not been determined in haematopoietic stem cell transplantation (HSCT) for adult acute lymphoblastic leukemia (ALL) patients.MethodsTo evaluate heterogeneous effects of intensified MAC among individuals, we analyzed the registry database of adult ALL patients between 2000 and 2021. After propensity score matching, we applied a machine-learning Bayesian causal forest algorithm to develop a prediction model of individualized treatment effect (ITE) of intensified MAC on reduction in overall mortality at 1 year after HSCT.ResultsAmong 2440 propensity score-matched patients, our model shows heterogeneity in the association between intensified MAC and 1-year overall mortality. Individuals in the high-benefit group (n = 1220), defined as those with ITEs greater than the median, are more likely to be younger, male, and to have higher refined Disease Risk Index (rDRI), T-cell phenotype, and grafts from related donors than those in the low-benefit group (n = 1220). The high-benefit approach (applying intensified MAC to individuals in the high-benefit group) shows the largest reduction in overall mortality at 1 year (risk difference [95% confidence interval], +5.94 percentage points [0.88 to 10.51], p = 0.011). In contrast, the high-risk approach (targeting patients with high or very high rDRI) does not achieve statistical significance (risk difference [95% confidence interval], +3.85 percentage points [−1.11 to 7.90], p = 0.063).ConclusionsThese findings suggest that the high-benefit approach, targeting patients expected to benefit from intensified MAC, has the capacity to maximize HSCT effectiveness using intensified MAC.