Iranian Journal of Pediatric Hematology & Oncology

Aberrant Immunophenotype in Childhood Acute Lymphoblastic Leukemia: Overall Survival and Disease-Free Survival up to 18 Months after Diagnosis

2025-12-14T09:18:35+00:00

Background: Aberrant immunophenotype, characterized by the expression of lineage-inappropriate antigens on leukemic blasts, is associated with early relapse and a poor survival rate in Acute Lymphoblastic Leukemia (ALL). Early relapse gives a bad prognosis for ALL. This study evaluated the association between aberrant immunophenotype and Overall Survival (OS) and Disease-Free Survival (DFS) up to 18 months following the diagnosis of ALL.

Materials and Methods: A retrospective cohort study was conducted to identify aberrant immunophenotype in 156 patients under 18 years of age with ALL. In this study, done at a tertiary level hospital, OS and DFS were analyzed using the Kaplan-Meier method, the Breslow test and a Cox regression model, with hazard ratios to determine the variables associated with mortality and relapse over an 18-month follow-up period.

Results: The mean age at diagnosis was 6.5 years, and 57% of the patients were male. Aberrant immunophenotype was expressed in 87 patients. After 18 months of follow-up, 41 patients had died. The CD123 antigen was mostly associated with relapses (p=0.010). CD66c and CD123 co-expression decreased OS (p=0.040) and DFS (p=0.003). The univariate analysis demonstrated that CD66c and CD123 co-expression (p=0.005), single CD123 expression (p=0.001), and positive Measurable Residual Disease (MRD) (p=0.001) increased the risk of relapse. In a multivariable analysis, only risk stratification and MRD remained as independent predictors of OS and DFS.

Conclusion: CD66c and CD123 co-expression was associated with decreased OS and DFS and a higher risk of relapse. However, this association did not remain significant in the multivariate model, indicating that it is not an independent prognostic factor. Nonetheless, isolated CD123 expression was linked to positive MRD and an increased risk of relapse. These observations provide clinically relevant preliminary insights, particularly in settings with survival disparities. These require confirmation in larger cohorts with extended follow-up and integrated molecular data.

Transcriptomic Profiling of Pediatric Acute Lymphoblastic Leukemia Subtypes Identifies Novel Prognostic Markers

2025-12-14T09:18:34+00:00

Background: Pediatric acute lymphoblastic leukemia (ALL) encompasses more than 20 molecular subtypes with diverse genetic and prognostic profiles. The 11q subtype, characterized by KMT2A rearrangements, exhibits an aggressive clinical course compared with favorable subtypes such as high hyperdiploidy (HeH) and dic (9; 20). This study aimed to elucidate the distinct transcriptomic signature of the 11q-rearranged pediatric ALL subtype relative to HeH and dic (9; 20) to identify novel prognostic markers.

Materials and Methods: Comparative observational study was done by gene expression profiles of 11q ALL (n = 5) were compared with dic (9; 20) ALL (n = 6) and HeH ALL (n = 18) using the GEO2R tool on the GSE47051 microarray dataset. Differentially expressed genes (DEGs) were defined as those with p < 0.05 and |log₂ fold change| > 1.0. Common DEGs across both comparisons were identified using Venny 2.1.0, and their protein–protein interaction networks and functional enrichment were analyzed using STRING.

Results: A total of 241 common DEGs were identified in 11q ALL, including 151 upregulated and 90 downregulated genes (p < 0.05). Prominent upregulated genes included members of the HOXA cluster (HOXA3, HOXA4, HOXA5, HOXA7, HOXA10) and MEIS1 (p = 0.001), reflecting activation of leukemogenic transcriptional programs. Conversely, genes involved in B-cell differentiation, such as BLNK and MS4A1/CD20, were significantly downregulated (p = 0.004). Enrichment analysis revealed that upregulated genes were significantly associated with focal adhesion, protein kinase binding, and cell migration pathways (p < 0.01), while downregulated genes were linked to B-cell activation, DNA repair, and chromosomal stability (p < 0.05).

Conclusion: The 11q-rearranged ALL subtype demonstrates a distinct transcriptional landscape characterized by HOXA–MEIS1 axis activation and suppression of normal B-cell signaling. These transcriptomic alterations likely underpin its aggressive phenotype and could inform risk stratification and targeted therapeutic development for high-risk pediatric ALL patients.

The Comparison of Genes and Molecular Pathway between Newly Diagnosed and Relapsed Acute Lymphocytic Leukemia (ALL) Patients: A Bioinformatics Analysis

2025-12-14T09:18:33+00:00

Background: Acute lymphoblastic leukemia (ALL) is among the most common cancers in children, which leads to the death of many patients. ALL patients include new cases and the relapsed ones. The common genes between these two conditions can largely help in managing patients and preventing future relapses. Therefore, this study investigated the genes and molecular pathways between the two conditions using bioinformatics.

Materials and Methods: In this bioinformatic study, GSE102301 database was used. After determining differentially expressed genes (DEGs), gene ontology (GO) and the related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed (using GeneCodis4 software). Interactions between proteins were evaluated using STRING database and hub genes were identified based on the highest score. Finally, ROC curve analysis was used to determine the diagnostic value of hub genes.

Results: Based on the interaction between DEGs, 10 genes were selected as hubs, which included WDR75, MYBBP1A, DDX10, URB1, HEATR1, NOP14, PUM3, VARS1, EARS2 and SYK |logFC| > 1 and p < 0.05. The results showed that all the hub genes had diagnostic value (AUC=1).

Conclusion: Hub genes identified through bioinformatics analyses may serve as potential biomarkers; however, future studies need to examine these genes in clinical settings among the patients.

Evaluation of Prognostic Factors in Children with Acute Lymphoblastic Leukemia

2025-12-14T09:18:32+00:00

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Despite major therapeutic advancements, relapse and treatment failure continue to be serious challenges, particularly in low- and middle-income countries. While several well-established prognostic factors such as age, white blood cell (WBC) count, cytogenetic abnormalities, minimal residual disease (MRD), and socioeconomic status (SES) have been validated in high-income regions, limited evidence is available from developing countries. Therefore, this study aimed to investigate the prognostic factors associated with relapse and mortality in children diagnosed with ALL in a developing country setting.

Materials and Methods: This prospective cohort study included 130 children younger than 15 years with confirmed ALL admitted to a tertiary referral center from 2014 to 2020. Demographic, clinical, laboratory, MRD, genetic, and socioeconomic data were collected from the patients, and they were followed for up to 48 months after achieving remission. Univariate and multivariate Cox regression models were used to identify the independent predictors of relapse and mortality (significance threshold: p < 0.05).

Results: The mean age of the participants was 4.76 ± 3.36 years, and relapse or death occurred in 31 (23.8%) of them. The univariate analysis showed that older age, MRD > 0.1% on day 33, and higher hemoglobin level were associated with relapse. The multivariate analysis identified MRD > 0.1% on day 33 as the only significant independent predictor of relapse. A survival analysis via a multivariate Cox-regression model also showed a lower income level (HR = 2.150, p = 0.033) associated with a higher mortality.

Conclusion: This study reveals MRD on day 33 as the strongest determinant of relapse and highlights the critical role of socioeconomic disparities in mortality among children with ALL in developing countries. Early MRD-based risk stratification and policies aimed at bridging socioeconomic gaps may contribute to improved survival outcomes. Larger multicenter studies and extended molecular profiling are recommended.

Cis and Trans Variants of α-Thalassemia Minor: “Hematological Differences and Distinction from Iron Deficiency Anemia

2025-12-14T09:18:31+00:00

Background: Alpha thalassemia and iron deficiency anemia (IDA) are common hematological disorders characterized by microcytic red blood cells, complicating accurate diagnosis. This study investigates the genetic diversity and clinical presentation of alpha thalassemia, emphasizing the critical need for precise differential diagnosis between alpha thalassemia and IDA to ensure effective patient management and treatment.

Materials and Methods: In this cross-sectional study, we conducted analysis of alpha thalassemia minor and IDA, focusing on hematological indices and clinical outcomes. Patients diagnosed with either condition from 2019 to 2023 were evaluated based on key parameters, including hemoglobin (Hb), red blood cell (RBC) count, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). We also analyzed alpha thalassemia genotypes, distinguishing between cis and trans variants. This study uniquely explores hematological profiles in thalassemia minor patients.

Results: Patients with cis-α-thalassemia exhibited lower MCV (68.14 ± 3.77 fL) compared to trans-α-thalassemia (72.15 ± 4.03 fL; p = 0.143). MCH was significantly lower in cis (20.58 ± 1.49 pg) than in trans (22.36 ± 1.43 pg; p = 0.013). Mean Hb was reduced in cis (12.10 ± 1.50 g/dL) relative to trans (12.46 ± 1.16 g/dL; p = 0.015), while RBC counts were higher in both alpha-thalassemia groups. Compared with IDA, alpha-thalassemia patients demonstrated significantly higher RBC counts (5.65 ± 0.44 vs. 4.30 ± 0.46 × 10¹²/L; p < 0.001) and Hb levels (12.37 ± 1.12 vs. 9.60 ± 1.12 g/dL; p < 0.001). Differences in MCV and MCH between thalassemia and IDA were not statistically significant.

Conclusion: This finding highlights significant hematological differences between alpha thalassemia variants and IDA. By elucidating the distinct features of cis and trans alpha thalassemia genotypes, this study reinforces the necessity for precise diagnosis and tailored clinical management. Further research is warranted to explore the long-term clinical implications of these genetic variants.

Association of Body Composition and Biochemical Indicators with Serum Ferritin Levels in Patients with β-thalassemia Major: A Cross-Sectional Study

2025-12-14T09:18:30+00:00

Background: This study aimed to assess the body composition and biochemical markers of patients with β-thalassemia major (BTM) in relation to their serum ferritin levels.

Materials and Methods: In this cross-sectional study, 74 BTM patients referred to an educational hospital in the southwest of Iran. They were grouped based on their serum ferritin levels. Given the cutoff point of 1500 ng/mL, 34 patients with acceptable serum ferritin level while 40 with high serum ferritin level. Anthropometric and biochemical indicators were collected following standard protocols. Dietary intake and body composition were evaluated by a 24-hour food recall and bioelectrical impedance analysis (BIA), respectively. The predictors of the serum ferritin level were determined by multivariate binary logistic regression, with the significance set at P < 0.05.

Results: Of the BTM patients, 16 (21.6%), 51 (68.9%) and 7 (9.5) were underweight, normal weight and overweight, respectively and no one them were obese. The daily intakes of vitamin K, vitamin D, vitamin B6 and copper were different significantly between two groups (P < 0.05). The mean blood transfusion interval was longer in acceptable ferritin level group compared to high ferritin group (P = 0.04). Fatness (P = 0.02) and total body water to lean body mass ratio (TBW/LBM) (P = 0.047) differed significantly between two groups. In fully adjusted regression model, the participants in the upper median group of fatness showed 81% lower odds ratio(OR) for high serum ferritin level (OR: 0.19, %95 confidence interval(CI): 0.033-0.84, P = 0.03). The association between TBW/LBM and serum ferritin level was positive, but not statistically significant in the fully adjusted model (OR: 3.66; 95% CI: 0.8–16.7; P = 0.096).

Conclusion: High body fat percent (BFP) is significantly associated with the lower odds of high ferritin levels, suggesting a potential protective role in BTM patients.

Multisystem Inflammatory Syndrome in Children (MIS-C): A Review of Short- and Long-Term Complications

2025-12-14T09:18:29+00:00

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare but serious post-infection disorder associated with SARS-CoV-2 infection, typically occurring 2-6 weeks after acute COVID-19. The syndrome is characterized by persistent fever, multisystem organ impairment, and laboratory evidence of inflammation. The affected individuals require prompt diagnosis and treatment to avoid morbidity. The short-term complications are widespread during the acute phase of the disease, often requiring intensive care. Cardiovascular symptoms occur in up to 80% of the cases. Gastrointestinal presentations are common along with respiratory, neurologic, renal and mucocutaneous complications.

Hematologic complications are one of the most frequent organ system presentations of MIS-C. They occur in over 50% of patients and pose significant thrombotic risks. Thrombocytopenia is observed in approximately 40-60% of patients, frequently with coagulopathy and elevated D-dimer, indicating a hypercoagulable state. There is a heightened prevalence of thromboembolic events in the form of deep vein thrombosis or pulmonary embolism due to endothelial injury and cytokine storms. These features point to the prothrombotic profile of MIS-C, which is distinct from other pediatric inflammatory syndromes. Also, late sequelae, an inadequately researched subject, include chronic cardiac defects, such as dilatation of coronary arteries or reduced ventricular function in 10-20% of survivors, who require ongoing echocardiography. Respiratory, gastrointestinal, and neurocognitive dysfunctions have been reported in follow-up observations, although most children return to normal after a few months. Hematological recovery is typically excellent, but chronic thrombotic risks exist in only some serious cases of the disease. While the short-term prognosis of MIS-C is generally favorable, uncertainties persist regarding its long-term complications. Standardized follow-up protocols for the complications of MIS-C are warranted to detect subclinical abnormalities and guide ongoing management. Continued surveillance and longitudinal research are essential to fully elucidate the natural history of the disease and optimize the outcomes for the survivors.

Vitamin B 12 Deficiency Presenting as Failure to Thrive, Regression of Milestones, and Severe Hemolytic Anemia in an Infant: A Case Report

2025-12-14T09:18:27+00:00

Vitamin B12 is essential for DNA synthesis and is necessary for the development of the central nervous system. Vitamin B12 deficiency occurs in babies who are exclusively breast-fed by mothers with insufficient stores of vitamin B12. In vitamin B12 deficiency, the clinical features are mainly hematological and neurological. Megaloblastic anemia is the characteristic feature of vitamin B12 insufficiency. Rare haematological manifestations include pancytopenia and hemolytic anemia. The other clinical spectrum of vitamin B12 deficiency comprises vomiting, lethargy, failure to thrive, hypotonia, and retrogression of developmental milestones. We reported a 7-month-old infant with vitamin B12 deficiency who presented with loss of weight and regression of social smile since one month of age. Her weight, length, and head circumference were in the less than 3^rd centile range according to the World Health Organisation (WHO) growth chart. She had severe pallor, hyperpigmentation of palms, soles, and knuckles, brownish depigmented brown sparse hair, and hepato-splenomegaly of 4 cm each. The laboratory results revealed Hb of 3.5gm/dl, Mean Corpuscular Volume (MCV) of 99fl, thrombocytopenia, normal ferritin levels, and peripheral smear showed polychromatophils, 19 nucleated Red Blood Cell (RBCs)/100White Blood Cells (WBCs), macrocytes, leucocytes shift to the left with 21% hypersegmented neutrophils, suggestive of hemolytic anemia. Vitamin B12 levels were 146pg/ml [N=200-900 pg/ml]. The baby started smiling 2 days after the vitamin B12 injection, gained 700 g during the follow-up of 3 months, and the pigmentation disappeared from the palms and soles.