Pediatric Acute Lymphoblastic Leukemia Research Articles

Molecular and cellular mechanisms of chemoresistance in paediatric pre-B cell acute lymphoblastic leukaemia.

Paediatric patients with relapsed B cell acute lymphoblastic leukaemia (B-ALL) have poor prognosis, as relapse-causing clones are often refractory to common chemotherapeutics. While the molecular mechanisms leading to chemoresistance are varied, significant evidence suggests interactions between B-ALL blasts and cells within the bone marrow microenvironment modulate chemotherapy sensitivity. Importantly, bone marrow mesenchymal stem cells (BM-MSCs) and BM adipocytes are known to support B-ALL cells through multiple distinct molecular mechanisms. This review discusses the contribution of integrin-mediated B-ALL/BM-MSC signalling and asparagine supplementation in B-ALL chemoresistance. In addition, the role of adipocytes in sequestering anthracyclines and generating a BM niche favourable for B-ALL survival is explored. Furthermore, this review discusses the role of BM-MSCs and adipocytes in promoting a quiescent and chemoresistant B-ALL phenotype. Novel treatments which target these mechanisms are discussed herein, and are needed to improve dismal outcomes in patients with relapsed/refractory disease.

Exploration of the intracellular chiral metabolome in pediatric BCP-ALL: a pilot study investigating the metabolic phenotype of IgH locus aberrations.

Aberrations in the immunoglobulin heavy chain (IgH) locus are associated with poor prognosis in pediatric precursor B-cell acute lymphoblastic leukemia (BCP-ALL) patients. The primary objective of this pilot study is to enhance our understanding of the IgH phenotype by exploring the intracellular chiral metabolome. Leukemia cells were isolated from the bone marrow of BCP-ALL pediatric patients at diagnosis. The samples' metabolome and transcriptome were characterized using untargeted chiral metabolomic and next-generation sequencing transcriptomic analyses. For the first time D- amino acids were identified in the leukemic cells' intracellular metabolome from the bone marrow niche. Chiral metabolic signatures at diagnosis was indicative of a resistant phenotype. Through integrated network analysis and Pearson correlation, confirmation was obtained regarding the association of the IgH phenotype with several genes linked to poor prognosis. The findings of this study have contributed to the understanding that the chiral metabolome plays a role in the poor prognosis observed in an exceptionally rare patient cohort. The findings include elevated D-amino acid incorporation in the IgH group, the emergence of several unknown, potentially enantiomeric, metabolites, and insights into metabolic pathways that all warrant further exploration.

Systematic review: genetic polymorphisms in the pharmacokinetics of high-dose methotrexate in pediatric acute lymphoblastic leukemia patients.

Variations in pharmacokinetic responses to high-dose methotrexate are essential for the prognosis and management of toxicity in the treatment of pediatric acute lymphoblastic leukemia (ALL) patients. This systematic review aimed to identify and evaluate genetic polymorphisms that are significantly associated with the pharmacokinetic parameters of methotrexate during the consolidation phase of pediatric ALL treatment. Using the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, we systematically reviewed the literature from 2013 to 2023. The databases used were PubMed and Scopus. The outcomes of interest are the study design, patient characteristics, sample size, chemotherapy protocol utilized, pharmacokinetic parameters identified, and genetic polymorphisms implicated. We included 31 articles in the qualitative synthesis and found that the SLCO1B1, ABCB1, ABCC2, and MTHFR genes appear to play significant roles in MTX metabolism and clearance. Among these, variations in SLCO1B1 have the most significant and consistent impact on methotrexate clearance. These implicated variants may contribute to the precision and tailoring of HD-MTX treatment in pediatric ALL patients.

Universal Targeted Haplotyping by Droplet Digital PCR Sequencing and Its Applications in Noninvasive Prenatal Testing and Pharmacogenetics Analysis.

The analysis of haplotypes of variants is important for pharmacogenomics analysis and noninvasive prenatal testing for monogenic diseases. However, there is a lack of robust methods for targeted haplotyping. We developed digital PCR haplotype sequencing (dHapSeq) for targeted haplotyping of variants, which is a method that compartmentalizes long DNA molecules into droplets. Within one droplet, 2 target regions are PCR amplified from one template molecule, and their amplicons are fused together. The fused products are then sequenced to determine the phase relationship of the single nucleotide polymorphism (SNP) alleles. The entire haplotype of 10s of SNPs can be deduced after the phase relationship of individual SNPs are determined in a pairwise manner. We applied dHapSeq to noninvasive prenatal testing in 4 families at risk for thalassemia and utilized it to detect NUDT15 diplotypes for predicting drug tolerance in pediatric acute lymphoblastic leukemia (72 cases and 506 controls). For SNPs within 40 kb, phase relation can be determined with 100% accuracy. In 7 trio families, the haplotyping results for 97 SNPs spanning 185 kb determined by dHapSeq were concordant with the results deduced from the genotypes of both parents and the fetus. In 4 thalassemia families, a 19.3-kb Southeast Asian deletion was successfully phased with 97 downstream SNPs, enabling noninvasive determination of fetal inheritance using relative haplotype dosage analysis. In the NUDT15 analysis, the variant status and phase of the variants were successfully determined in all cases and controls. The dHapSeq represents a robust and scalable haplotyping approach with numerous clinical and research applications.

Flow cytometric evaluation of the CD34 marker as a prognostic factor in pediatric acute lymphoblastic leukemia, Baghdad 2021

Flow cytometric evaluation of the CD34 marker as a prognostic factor in pediatric acute lymphoblastic leukemia, Baghdad 2021

Disease-burden-adapted immunotherapy protocol for primary refractory or high-risk relapsed pediatric acute lymphoblastic leukemia.

Disease-burden-adapted immunotherapy protocol for primary refractory or high-risk relapsed pediatric acute lymphoblastic leukemia.

Acute Pancreatitis in Pediatric Acute Lymphoblastic Leukemia (AcuPA Study): A Nationwide Survey in Poland.

This study aimed to identify the risk factors for acute pancreatitis (AP) and its impact on outcomes in Polish children treated for ALL. The study group included 2303 children receiving intensive chemotherapy for ALL. The group was divided into patients with at least one episode of AP and those who did not develop AP after treatment for ALL. The cumulative incidence of AP in the study group was 4.08%. Older age was an independent risk factor for the development of AP (OR = 1.05; 95%CI = 1.006-1.098; p = 0.03). The overall mortality associated with AP was 2.13%. The probabilities of disease-free survival (p-DFS) and event-free survival (p-EFS) in both subgroups were 0.84 vs. 0.86, log-rank p = 0.65 and 0.75 vs. 0.80, log-rank p = 0.12, respectively. A total of 22 out of 94 patients (23.4%) with AP were re-exposed to asparaginase (ASP) during the subsequent treatment phases. Only one patient re-exposed to ASP (4.5%) developed a second episode of AP. There were no significant differences in p-DFS and p-EFS between patients re-exposed and not re-exposed to asparaginase (0.78 vs. 0.86, log-rank p = 0.27 and 0.63 vs. 0.79, log-rank p = 0.09, respectively). The incidence of AP in children with ALL is low and related to patients' age. The development of AP does not seem to influence p-DFS and p-EFS in children with ALL. Recurrence of AP after re-exposure to asparaginase in patients with ALL and a history of AP is low (4.5%). Re-exposure to asparaginase after the first episode of AP does not improve either p-DFS or p-EFS in children with ALL.

Blinatumomab vs Chemotherapy for Pediatric and Adult Acute Lymphoblastic Leukemia

Blinatumomab vs Chemotherapy for Pediatric and Adult Acute Lymphoblastic Leukemia

The Role of PTEN in Chemoresistance Mediated by the HIF-1α/YY1 Axis in Pediatric Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Current chemotherapy treatment regimens have improved survival rates to approximately 80%; however, resistance development remains the primary cause of treatment failure, affecting around 20% of cases. Some studies indicate that loss of the phosphatase and tensin homolog (PTEN) leads to deregulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, increasing the expression of proteins involved in chemoresistance. PTEN loss results in deregulation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and induces hypoxia-inducible factor 1-alpha (HIF-1α) expression in various cancers. Additionally, it triggers upregulation of the Yin Yang 1 (YY1) transcription factor, leading to chemoresistance mediated by glycoprotein p-170 (Gp-170). The aim of this study was to investigate the role of the PTEN/NF-κB axis in YY1 regulation via HIF-1α and its involvement in ALL. A PTEN inhibitor was administered in RS4;11 cells, followed by the evaluation of PTEN, NF-κB, HIF-1α, YY1, and Gp-170 expression, along with chemoresistance assessment. PTEN, HIF-1α, and YY1 expression levels were assessed in the peripheral blood mononuclear cells (PBMC) from pediatric ALL patients. The results reveal that the inhibition of PTEN activity significantly increases the expression of pAkt and NF-κB, which is consistent with the increase in the expression of HIF-1α and YY1 in RS4;11 cells. In turn, this inhibition increases the expression of the glycoprotein Gp-170, affecting doxorubicin accumulation in the cells treated with the inhibitor. Samples from pediatric ALL patients exhibit PTEN expression and higher HIF-1α and YY1 expression compared to controls. PTEN/Akt/NF-κB axis plays a critical role in the regulation of YY1 through HIF-1α, and this mechanism contributes to Gp-170-mediated chemoresistance in pediatric ALL.

Immunotherapies for Childhood Cancer.

Children are surviving cancer in greater numbers than ever. Over the last 50 years, substantial advancements in pediatric cancer treatment have resulted in an 85% 5-year survival rate. Nonetheless, a notable 10%-15% of patients encounter relapse or develop refractory disease, leading to significantly lower survival. Recent attempts to further intensify cytotoxic chemotherapy have failed due to either severe toxicities or ineffectiveness, highlighting the need for new treatment strategies. Immunotherapies are emerging and expanding their clinical application to a wide array of cancers, including those affecting children. In pediatric cancers, monoclonal antibodies targeting GD2 have demonstrated durable radiographic and histologic responses in neuroblastoma (NB), and CD19-targeted bispecific antibodies (BsAbs) and chimeric antigen receptor (CAR) T cells have likewise changed the outlook for refractory acute lymphoblastic leukemia (ALL) in children. This review discusses the clinical development of immunotherapies for pediatric cancers, focusing on pediatric ALL and NB, two major pediatric cancers transformed by immunotherapy, updates on the recent advancements in immunotherapies, and further discusses the future directions of immunotherapy for pediatric cancers.

Use of allopurinol to manage skewed 6-mercaptopurine metabolism in pediatric maintenance acute lymphoblastic leukemia treatment.

6-mercaptopurine is a cornerstone of maintenance therapy for pediatric ALL. Response to 6MP is typically determined by the ANC. Therapeutic ANC range while receiving 6MP is between 500 and 1500/μL. In addition to desired myelosuppression, 6MP is associated with multiple adverse drug effects. Increased doses of 6MP can lead to therapeutic ANC values; however, patients may experience adverse effects before obtaining therapeutic myelosuppression, often deemed "skewed metabolism." Allopurinol may potentially correct skewed 6MP metabolism. Pediatric patients with ALL with 6MMP and 6TGN metabolites drawn during maintenance therapy were analyzed for allopurinol use. The primary outcome evaluated the percentage of time spent in therapeutic ANC range before and after allopurinol initiation. In addition, the difference in 6MMP:6TGN ratios before and after allopurinol initiation, incidence of hepatotoxicity, and rates of relapse, were analyzed. Ninety-five patients were included for analysis. Thirty-two (34%) patients received allopurinol. There were no significant differences in baseline demographics between the patients who received allopurinol and those who did not. When comparing ANC values pre- and post-allopurinol initiation, a statistically significant increase in the percentage of time spent in therapeutic range was observed (27% vs. 43%; p = .03). In addition, when comparing metabolite ratios pre- and post-allopurinol initiation, a statistically significant decrease in 6MMP:6TGN metabolite ratio values was observed (86.7 vs. 3.6; p < .0001). Allopurinol significantly increased the percent time in therapeutic ANC range and can be safely utilized to significantly lower the ratio of 6MMP:6TGN metabolites, alleviating the undesirable side effects of 6MMP, and optimizing the anti-leukemic effects associated with 6TGN.

The Effect of Hematopoietic Stem Cell Transplantation on Treatment Outcome in Children with Acute Lymphoblastic Leukemia.

Hematopoietic stem cell transplantation (HSCT) has been an important method of treatment in the advance of pediatric acute lymphoblastic leukemia (ALL). The indications for HSCT are evolving and require updated establishment. In this study, we aimed to investigate the efficacy of HSCT on the treatment outcome of pediatric ALL, considering the indications for HSCT and subgroups. A retrospective analysis was conducted on ALL patients diagnosed and treated at a single center. Risk groups were categorized based on age at diagnosis, initial white blood cell count, disease lineage (B/T), and cytogenetic study results. Data on the patients' disease status at HSCT and indications of HSCT were collected. Indications for HSCT were categorized as upfront HSCT at 1st complete remission, relapse, and refractory disease. Among the 549 screened patients, a total of 418 patients were included in the study; B-ALL (n=379) and T-ALL (n=39). HSCT was conducted on a total of 106 patients (25.4%), with a higher frequency as upfront HSCT in higher risk groups and specific cytogenetics. The overall survival (OS) was significantly better when done upfront than in relapsed or refractory state in T-ALL patients (p=0.0016). The KMT2A-rearranged ALL patients showed superior event-free survival (p=0.0023) and OS (p=0.0221) when HSCT was done as upfront treatment. HSCT had a substantial positive effect in a specific subset of pediatric ALL. In particular, frontline HSCT for T-ALL and KMT2A-rearranged ALL offered a better prognosis than when HSCT was conducted in a relapsed or refractory setting.

Serum Stabilin1 as a Prognostic Marker in Adults Acute Leukemia Patients

Abstract Background STAB-1 (common lymphatic endothelial and vascular endothelial receptor) was found to be expressed on tumor lymphatic vessels in different malignancies and it is a bad prognostic marker. This study will assess the role of serum stabilin1 (STAB1) as a prognostic marker in adult patients with newly diagnosed acute leukemia and correlate it with the other well established prognostic markers. Acute lymphoblastic leukemia (ALL) is a hematologic malignancy arising from precursors of the lymphoid lineage. Conventional cytotoxic chemotherapies have resulted in high cure rates of up to 90% in pediatric ALL, but the outcomes for adult patients remain suboptimal with 5-year survival rates of only 30%-40%. Aim of the Work To measure STAB1 expression in patients with AML and patients with ALL and assess its role as a prognostic factor with correlating it with other prognostic factors. Patients and Methods A case control study in Ain Shams University Hospitals, Clinical Haematology and Oncolgy division of Internal Medicine Department for one year on total 75 subjects divided into: 25 patients with newly diagnosed acute myeloid leukemia (AML), 25 patients with newly diagnosed acute lymphoblastic leukemia (ALL) and 25 age and sex matched healthy control subjects. The study population was recruited from Ain Shams University Hospitals, Clinical Haematology and Oncolgy division of Internal Medicine Department. Results There was no significant difference between cases of acute leukemia pts and control group as there was no statistically significant difference between control and patients group regarding sex, age, spleen size, liver size, LDH, CRP, uric acid and ESR of the studied subjects. Our study shows that as regard CBC; there was significant difference between the studied groups as regard leucocytic count, BUT Platelets, and hemoglobin was insignificant, which was also described in the study. Our study showed that there was high statistically significant difference between the acute leukemia patients and the healthy control group as regard sabilin1. Our study shows that the mean serum level of stabilin1 in the patients who didn’t respond to chemotherapy was higher than that of the patients that responded to chemotherapy. Conclusion There was high statistically significant difference between the studied groups as stabilin1. There was significant correlation between stabilin2 and chemotherapy response. Stabilin1 expression levels also identified a new subgroup at a higher risk for relapse and with a poor prognosis in acute leukemia patients. Stabilin 1 can be used as a prognostic factor in patients with acute leukemia.

The impact of comparative genomic hybridization/single-nucleotide polymorphism microarray in risk stratification of pediatric acute lymphoblastic leukemia.

The objective of this study is to assess the concordance and added value of combined comparative genomic hybridization plus single-nucleotide polymorphism microarray (CGH/SNP) analyses in pediatric acute lymphoblastic leukemia (ALL) risk stratification compared to conventional cytogenetic methods. This is a retrospective study that included patients aged 1-18years diagnosed with de novo ALL at Sainte-Justine Hospital between 2016 and 2021. Results from conventional cytogenetic and molecular analyses were collected and compared to those of CGH/SNP. A total of 135 ALL patients were included. Sample failures or non-diagnostic analyses occurred in 17.8% cases with G-banding karyotypes versus 1.5% cases with CGH/SNP. The mean turnaround time for results was significantly faster for CGH/SNP than karyotype with 5.8 versus 10.7days, respectively. The comparison of ploidy assessment by CGH/SNP and G-banding karyotype showed strong concordance (r=.82, p<.001, r2=.68). Furthermore, G-banding karyotype did not detect additional clinically relevant aberrations that were missed by the combined analysis of CGH/SNP and fluorescence in situ hybridization. The most common gene alterations detected by CGH/SNP were deletions involving CDKN2A (35.8%), ETV6 (31.3%), CDKN2B (28.4%), PAX5 (20.1%), IKZF1 (12.7%), and copy-neutral loss of heterozygosity (CN-LOH) of 9p (9.0%). Among these, only ETV6 deletion was found to have a significant prognostic impact with superior event-free survival in both univariate and multivariate analyses (adjusted hazard ratio 0.08, 95% confidence interval: 0.01-0.50, p=.02). CGH/SNP provided faster, reliable, and highly concordant results than those obtained by conventional cytogenetics. CGH/SNP identified recurrent gene deletions in pediatric ALL, of which ETV6 deletion conferred a favorable prognosis.

Genetic Susceptibility and Treatment Personalization in Acute Lymphoblastic Leukemia: A Comprehensive Review of Genetic Susceptibility and Targeted Therapies

Abstract Acute lymphoblastic leukemia (ALL) in children is a complicated and heterogeneous disease impacted by various genetic susceptibility factors. The significance of genetic testing in pediatric ALL diagnosis and management, the role of minimal residual disease (MRD) monitoring, and ethical issues and problems in pediatric genetic testing are discussed in this narrative review. It also looks ahead to the future of genetic susceptibility research, focusing on data integration, artificial intelligence-driven insights, and the possible finding of novel treatment targets. We hope to provide a complete view of the current status and hopeful future of precision medicine in pediatric oncology as we traverse these numerous facets of pediatric ALL. Pediatric ALL is a significant problem in the world of pediatric cancer, requiring a detailed understanding of its genetic foundations and the importance of genetic testing. This narrative review investigates the complex world of pediatric ALL, shedding light on the intricate web of genetic susceptibility factors that influence the progression and treatment results. While we investigate the importance of genetic testing, the critical function of MRD monitoring, and the ethical concerns inherent in pediatric genetic testing, we also look forward to the potential horizons of genetic susceptibility research.

Unraveling Copy Number Alterations in Pediatric B-Cell Acute Lymphoblastic Leukemia: Correlation with Induction Phase Remission Using MLPA.

Acute Lymphoblastic Leukemia (ALL) is the most common malignancy occurring in children. Copy number alterations (CNA) like PAX5, CDKN2A/2B, PAR1 Region, ETV6, IKZF1, BTG1, and RB1 gene deletion are important genetic events that define and prognosticate B-cell ALL. Thus, this study aimed to evaluate associations of CNA with induction phase remission status in childhood B-cell ALL. This study was observational with a cross-sectional design at the Dharmais Cancer Hospital, Harapan Kita Mother and Children Hospital, and Tangerang Regional Public Hospital. We evaluated 74 pediatric B-cell ALL cases with 1-18-year-olds. Genomic DNA was analyzed by Multiplex Ligation Dependent Probe Amplification Assay (MLPA). This study used the P335 ALL-IKZF1 panel kit, which contains several ALL-related genes. The patient's clinical and laboratory characteristics were collected from medical records from January to December 2019. We observed gene copy number alteration in children with B-Cell ALL. PAX5 was the most commonly observed gene deletion, followed by CDKN21/2B, ETV6, IKZF1, BTG1, RB1, and PAR1 Region. Based on gene mutations, only the PAX5 had a significant association with the remission status of pediatric B-cell ALL (p-value <0.05; OR = 3.91). It showed that patients with PAX5 gene mutations have 3.9 times the risk of no remission and/or relapse compared to those without PAX5 gene mutations. Patients with mutations in the PAX5 gene have a higher chance of not achieving remission and/or experiencing relapse than those without such mutations. The MLPA method can be utilized for examining copy number alterations, which is valuable for achieving more precise stratification in diagnosis.. Further research is needed to expand upon this finding.

Synergistic drug interactions of the histone deacetylase inhibitor givinostat (ITF2357) in CRLF2-rearranged pediatric B-cell precursor acute lymphoblastic leukemia identified by high-throughput drug screening

Combining multiple drugs broadens the window of therapeutic opportunities and is crucial for diseases that are currently lacking fully curative treatments. A powerful emerging tool for selecting effective drugs and combinations is the high-throughput drug screening (HTP). The histone deacetylase inhibitor (HDACi) givinostat (ITF2357) has been shown to act effectively against CRLF2-rearranged pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), a subtype characterized by poor outcome and enriched in children with Down Syndrome, very fragile patients with a high susceptibility to treatment-related toxicity. The aim of this study is to investigate possible synergies with givinostat for these difficult-to-treat patients by performing HTP screening with a library of 174 drugs, either approved or in preclinical studies. By applying this approach to the CRLF2-r MHH-CALL-4 cell line, we identified 19 compounds with higher sensitivity in combination with givinostat compared to the single treatments. Next, the synergy between givinostat and the promising candidates was further validated in CRLF2r cell lines with a broad matrix of concentrations. The combinations with trametinib (MEKi) or venetoclax (BCL2i) were found to be the most effective and with the greatest synergy across three metrics (ZIP, HAS, Bliss). Their efficacy was confirmed in primary blasts treated ex vivo at concentration ranges with a safe profile on healthy cells. Finally, we described givinostat-induced modifications in gene expression of MAPK and BCL-2 family members, supporting the observed synergistic interactions. Overall, our study represents a model of drug repurposing strategy using HTP screening for identifying synergistic, efficient, and safe drug combinations.

Household Income Disparities in Childhood Acute Lymphoblastic Leukemia Incidence and Mortality: A US Population-Based Analysis between 2000 and 2020

Introduction: Acute Lymphoblastic Leukemia (ALL) is the most common childhood cancer with an annual incidence of 3.7-4.9 cases per 100,000. There are no recent reports of the effect of socioeconomic status on pediatric ALL incidence and mortality class. Objective: Assess the association between ALL incidence and mortality and the socioeconomic status in children ages 21 years and younger. Methods: Retrospective analysis was conducted of the Surveillance, Epidemiology and End Results (SEER) database, which represents up to 48% of the general US population. We included patients with ALL up to 21 years of age during 2000-2020. Patients were categorized based on annual household income into three groups: low-income: &lt; $50,000; middle-income: $50,000-$75,000; high-income: &gt;$75,000. Incidence and mortality rates were expressed per 100,000 person-years. Annual Percentage Changes (APCs) were defined as the average year-over-year rate change. Student’s t test was used to determine if APCs were significantly different from zero with a significance level of 0.05. Results: We reviewed 30,852 cases, of which 9%, 54%, and 37% belonged to low-, middle-, or high-income families, respectively, and with incidence rates of 3.2, 3.4, and 3.1 per 100,000 person-years, respectively. Incidence in low-income children showed a statistically significant average increase of 1.1% (p = 0.003) per year during 2000-2020, while it showed a significant increased followed by stable rates since 2007 and 2010 in middle- and high-income children, respectively. ALL mortality was 0.5, 0.4, and 0.4 per 100,000 person-years, in low-, middle-, and high-income children, respectively. Mortality in low-income children has increased 2000-2007 (APC= 25.2%, p = 0.011); it did not significantly change after that. Conclusions: ALL incidence in low-income children has been increasing and remained the highest while mortality improved in middle-income children. Differences in healthcare access may be associated with the findings; further studies are needed to delineate this further.

Global survival of pediatric patients with acute lymphoblastic leukemia from a Latin American Hospital

Background: Acute lymphoblastic leukemia (ALL) is the most common neoplasm in pediatric and adolescent populations. Overall survival has improved in recent decades. This study aimed to assess the overall survival of patients with pediatric ALL in a Latin American hospital. Materials and Methods: A longitudinal and retrospective analytical study was conducted on 31 patients less than 16 years of age diagnosed with ALL at the hematology department of a Peruvian hospital during the period 2015-2016. Overall survival at 5 years was determined using the Kaplan-Meier curve with parametric log-rank tests, and the Cox regression model was employed to ascertain the hazard ratios of significant variables. Results: The average age was 6 years, and 21 (67.7%) were female. The 5-year overall survival rate was 35%, with a median survival of 33 months (95% CI = 34.078-66.861). Being 10 years or older was associated with lower survival (p = 0.002). No significant association with B-cell acute lymphoblastic leukemia was found (p = 0.057). Conclusion: The overall survival rate obtained was similar to that reported in other local studies; however, several international studies have reported better survival rates compared to our findings. Age was identified as a significant factor affecting survival.

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 &lt;0.05). No significant relationship was observed between pulmonary dysfunction and other drugs (P&gt; 0.05). No correlation was found between pulmonary complications due to chemotherapy with duration of chemotherapy, patient age, and patient gender (P&gt; 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.