International Journal of Hematology-Oncology and Stem Cell Research

Rhesus Box as the Primary Mechanism of RHD Gene Deletion in RhD-Negative Blood Donors from Eastern Iran

Mobina Nakhaei Shamahmood — 2026-06-16

Background: The Rh blood group system is highly significant in transfusion medicine because of the strong immunogenicity of the D antigen. The RhD-negative phenotype arises through various molecular mechanisms in different populations, most commonly complete deletion of the RHD gene caused by unequal recombination between upstream and downstream Rhesus box sequences. Although this mechanism has been well documented in some populations, limited data are available from Iran, particularly its eastern regions. This study aimed to determine the molecular basis of the RhD-negative phenotype among blood donors in eastern Iran.

Materials and Methods: In this cross-sectional study, a total of 16,190 blood donors referred to blood transfusion centers in South Khorasan Province, eastern Iran, over a one-year period were screened serologically for RhD status. Among them, 2,198 individuals were identified as RhD-negative, and 100 serologically confirmed RhD-negative donors were randomly selected for molecular evaluation. RhD typing was performed using standard serologic methods and verified by indirect antiglobulin testing. Molecular investigations included PCR-SSP targeting RHD exons 5, 7, and 10, real-time PCR for confirmation, and PCR-RFLP to detect the hybrid Rhesus box and determine RHD zygosity.

Results: Among 16,190 blood donors screened during the study period, 2,198 (13.57%) were identified as RhD‑negative. From this group, 100 samples were randomly selected for molecular analysis. Both PCR‑SSP and real‑time PCR demonstrated the absence of RHD exons 5, 7, and 10 in all samples, indicating complete deletion of the RHD gene. PCR‑RFLP analysis further showed that all donors were homozygous for the hybrid Rhesus box, with full concordance observed between exon‑specific assays and hybrid Rhesus box genotyping.

Conclusion: These findings indicate that the RhD-negative phenotype is primarily due to homozygous RHD gene deletion mediated by the hybrid Rhesus box. Hybrid Rhesus box analysis may therefore serve as a reliable molecular marker for accurate RhD typing, improving transfusion safety and perinatal management.

MicroRNA-206 as a Novel Potential Prognostic Biomarker for Distinguishing Philadelphia Chromosome-Positive and Negative ALL Patients

Zahra Mohammadi — 2026-06-17

Background: MicroRNAs (miRNAs) are a group of small non-coding RNAs that control protein-coding gene expression, and alterations in their expression are associated with leukemic changes in hematopoietic cells. The current study was performed on bone marrow samples from Philadelphia chromosome-positive (Ph+) and Philadelphia chromosome-negative (Ph−) ALL patients to assess miR-320a and miR-206, as well as their relationship with the prognosis of ALL.

Materials and Methods: miR-206 and miR-320a expression levels were assessed using Real-Time PCR in 50 bone marrow specimens from 10 healthy individuals (as a control group), 20 Ph+ ALL patients, and 20 Ph- ALL patients. The data were analyzed using GraphPad Prism version 7, one-way ANOVA, and Chi-square tests.

Results: The present study reports on the differential expression of miR-206 in Ph- and Ph+ ALL groups in comparison to normal individuals. The Ph- ALL group exhibited a significant 3.8-fold reduction in expression (P = 0.004), while the Ph+ ALL group demonstrated a noteworthy 5.34-fold increase in expression (P = 0.006) relative to the control group, although no statistically significant differences were observed in the comparison of miR-320a expression between Ph+ and Ph- patients (P = 0.496 and P = 0.645, respectively). Data analysis showed no relationship between age, sex, and miRNA expression.

Conclusion: MiR-206 showed a different expression pattern, and it seems that this miRNA was upregulated in Ph+ ALL and downregulated in Ph- ALL patients, and may serve as a potential prognostic and diagnostic biomarker for distinguishing between the two ALL groups.

Opportunistic Cervical Cancer Screening Using Liquid-Based Cytology in a Gynaecology Outpatient Setting: A Cross-Sectional Study

Kaustav Das — 2026-06-17

Background: Cervical cancer is a major public health issue, particularly in low- and middle-income countries. Early detection through effective screening methods is crucial for reducing morbidity and mortality. Opportunistic cervical cytology testing in outpatient settings plays an important role in the early identification of precancerous lesions.

Materials and Methods: This cross-sectional study aimed to evaluate the effectiveness of LBC in detecting precancerous lesions and cervical cancer in a defined population. One hundred women aged between 25 and 75 were screened using LBC. Cytological specimens were processed and analyzed by experienced cytopathologists.

Results: The primary outcome measures were the detection rate of precancerous lesions and cervical cancer, and the identification of factors associated with an increased risk of developing cervical cancer. Most of the patients who attended the OPD were in the fourth decade of life (37 cases, 37%), followed by 23 patients (23%) in the third decade. About 72.7% of patients who were diagnosed with LSIL and HSIL were in the age group of 51–70 years. Out of 100 patients, 13 had premalignant lesions and 2 had carcinoma.

Conclusion: The results of this study will provide valuable insights into the performance of LBC in a specific population setting. This information can contribute to the development and implementation of effective cervical cancer screening programs and ultimately reduce the burden of this disease.

Human Wharton’s Jelly Mesenchymal Stem Cells Improve Insulin Levels and Reduce Weight Gain in Aging Female Rats

Wining Astini — 2026-06-17

Background: This study aimed to analyze the effect of a single injection of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) at a dose of 1 × 10⁶ cells/kg on insulin levels and weight gain in physiologically aging female rats.

Materials and Methods: This study used a group of female rats (12 rats) divided into three groups: Group A (three-month-old young female rats with no treatment as control), Group B (24-month-old aging female rats injected with 0.9% NaCl in 0.4 mL as control), and Group C (24-month-old aging female rats injected with hWJ-MSCs at a dose of 1 × 10⁶ cells/kg in 0.4 mL as treatment). The injections were administered four times at three-month intervals. At the end of this experiment (12 months), the rats were anesthetized and sacrificed. Insulin levels were measured using ELISA. Immunohistochemical staining was performed to detect the homing of hWJ-MSCs in pancreatic tissue.

Results: The data showed that rats treated with hWJ-MSCs had lower weight compared with the control group. Insulin hormone levels in treated aging rats were significantly different from those in the aging control group. Immunohistochemical results showed that hWJ-MSCs were widely distributed in the islets of Langerhans of treated aging rats.

Conclusion: The results of this study indicate that body weight and insulin levels in physiologically aging female rats change with age. Wharton's jelly mesenchymal stem cells injected intravenously four times at a dose of 1 × 10⁶ cells/kg in physiologically aging female rats successfully migrated and homed to the islets of Langerhans, showed a trend toward reduced weight gain, and significantly increased insulin levels.

Observation of Hematologic Improvement with Luspatercept in Patients with Anemia from Diverse Hematologic Disorders: A Single-Center Retrospective Clinical Analysis

Guokai Zhang — 2026-06-17

Background: Anemia is a common clinical condition in hematology, associated with diverse etiologies and treatment strategies, many of which have notable limitations. Luspatercept, a novel erythroid maturation agent, has shown promise in treating anemia, particularly in patients with β-thalassemia and myelodysplastic syndromes (MDS). This study aimed to evaluate the real-world hematologic effectiveness of luspatercept across various anemia subtypes.

Materials and Methods: A retrospective observational study was conducted on 22 patients with anemia of different origins—MDS, post-hematopoietic stem cell transplantation (HSCT), aplastic anemia (AA), and T-cell large granular lymphocytic leukemia (T-LGLL)—who received luspatercept therapy at the 960th Hospital from June 2023 to January 2025. Hematologic improvement was assessed using the International Working Group (IWG) 2018 criteria for erythroid response (HI-E). Pre- and post-treatment changes in hemoglobin (Hb), reticulocyte percentage (RET %), and absolute reticulocyte count (RET #) were analyzed using the Wilcoxon Signed-Rank Test. Multivariate regression was employed to control for age, gender, and disease severity. Statistical significance was set at P ≤ 0.05, and all analyses were performed using SPSS version 27.0.

Results: Among the 22 patients, 10 (45.5%) had MDS (5 low-risk, 5 intermediate-to-high-risk), 6 (27.3%) post-HSCT anemia, 4 (18.2%) AA, and 2 (9%) T-LGLL. A total of 16 patients (72.7%) achieved a clinically meaningful erythroid response. Seven (43.8%) of these remained transfusion-independent until the last follow-up, with a median duration of 19.5 weeks (range: 8.6–47). Median time to initial response was 3.86 weeks (range: 0.57–25.57). Significant increases were observed in Hb (P < 0.001) and RET # (P = 0.001), while the increase in RET % did not reach statistical significance (P = 0.088). These findings support the efficacy of luspatercept in promoting erythropoiesis and improving anemia in a heterogeneous patient population.

Conclusion: Luspatercept demonstrated significant hematologic improvement, particularly in hemoglobin levels, in patients with anemia from various hematologic disorders. These results support its broader therapeutic potential. Future multicenter, prospective studies are warranted to validate its role in treating other forms of anemia.

Correlation of Biochemical and FDG PET/CT Responses Following Induction Therapy In Newly Diagnosed Multiple Myeloma: A Prospective Observational Study

Homdutt Sharma — 2026-06-20

Background: Multiple myeloma is a heterogeneous malignancy with patchy bone marrow involvement, often leading to discrepancies between biochemical and imaging-based response assessments. Site-specific bone marrow biopsies may miss focal disease, while FDG PET/CT detects metabolically active lesions, offering complementary prognostic value.

Materials and Methods: This prospective study included 44 newly diagnosed multiple myeloma patients. The primary aim was to assess the correlation between biochemical and PET/CT responses at six months post-induction. A secondary objective was to evaluate the impact of PET/CT response on 12-month EFS.

Results: The median age was 55.5 years. At baseline, >3 focal lesions and EMD were observed in 61.4% and 34.1% of patients, respectively. After six months of induction therapy, 86.3% achieved ≥VGPR biochemically, but 52.3% remained PET/CT-positive. Baseline >3 focal lesions and extramedullary disease (EMD) significantly predicted persistent PET/CT positivity (p = 0.004). Notably, 50% of patients with ≥VGPR (very good partial response) still showed PET/CT-positive findings. At 12 months, 75% of patients with clinical events had positive PET/CT at six months versus 47.2% without events (p = 0.245). Event-free survival was lower in the PET/CT-positive group (73.9% vs. 90.4%, p = 0.182), though not statistically significant.

Conclusion: 18-FDG PET/CT can detect residual disease not captured by biochemical markers, highlighting the value of combined assessment in multiple myeloma. Baseline >3 focal lesions and EMD predicted persistent PET/CT positivity. Although PET/CT positivity at six months showed a trend toward worse 12-month EFS, larger studies are needed to confirm its prognostic significance.

Outcome of Acute Myeloid Leukemia Treatment and IDH Mutations: A Systematic Review and Meta-Analysis Study

Fereshteh Ameli — 2026-06-20

Background: Acute myeloid leukemia (AML) is a heterogeneous disease with diverse genetic alterations influencing prognosis and treatment outcomes. Isocitrate dehydrogenase (IDH) genes, particularly IDH1 and IDH2, have emerged as important biomarkers, but the prognostic impact of their mutations remains controversial. This systematic review and meta-analysis aimed to evaluate the prognostic significance of IDH mutations in AML, focusing on overall survival (OS) and relapse-free survival (RFS).

Materials and Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science to identify eligible studies published up to February 2025. Studies reporting the association between IDH mutations (IDH1 and IDH2) and survival outcomes in AML were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted or derived when necessary.

Results: The analysis included 33 studies (n= 17,576). IDH2 mutations were associated with improved overall survival (HR = 0.70, 95% CI: 0.63–0.78) and relapse-free survival (HR = 0.65, 95% CI: 0.52–0.82), particularly in patients treated with IDH inhibitors. IDH1 mutations were linked to poor outcomes (OS HR = 1.16, 95% CI: 1.07–1.25; RFS HR = 1.03, 95% CI: 0.76–1.41). Subgroup analysis showed a more favorable prognosis for IDH2 R140 mutations, whereas IDH2 R172 mutations demonstrated heterogeneous outcomes across studies and treatment settings.

Conclusion: IDH mutations have a significant but heterogeneous prognostic impact in AML, with IDH2 mutations generally associated with better outcomes compared to IDH1 mutations. Larger, well-designed studies with comprehensive molecular profiling are needed to clarify the prognostic implications of IDH mutations in AML.

The Iranian National Guideline for Invasive Fungal Infections (IFI) in Hematology–Oncology: An Expert Consensus Report

Fereshteh Ghiasvand — 2026-06-20

Invasive fungal infections are a leading cause of death in patients with hematological malignancies and those receiving bone marrow transplants. Although standard guidelines exist globally, their direct application in Iran is not always possible due to differences in the types of common fungi and limited diagnostic and therapeutic facilities. To address this challenge, a national committee of experts in the field was formed to carefully review internationally recognized protocols published up to 2024 and solicit opinions from selected experts across the country to develop the first national guideline specifically for prophylaxis. To ensure methodological rigor, the Appraisal of Guidelines for Research and Evaluation II (AGREE II) framework and Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were utilized. The resulting consensus established a localized risk-stratification model identifying acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and active graft-versus-host disease (GVHD) patients as high-risk, recommending posaconazole as the primary standard. Notably, the guideline advises against routine azole use in acute lymphoblastic leukemia (ALL) to prevent neurotoxicity. Furthermore, a resource-tiered framework was developed for centers with varying diagnostic capabilities. The result of this effort was to present a tiered and local model that provides a practical solution for both well-equipped and limited facilities. The existence of this national guideline creates a major advantage in that treatment approaches are unified and standardized across the country. By eliminating discretionary decisions, this document helps to better manage medication use and ultimately improve patient outcomes, regardless of the city in which they are treated or the facilities they are treated at.

Role of Three-Dimensional Convolution Neural Networks (3D- CNN) in Image Processing and Recognition in Oncology: A Systematic Review and Meta-Analysis

Sanjeev Kumar Jain — 2026-06-20

Three-dimensional convolutional neural networks (3D CNNs) have transformed oncology imaging by offering superior performance in tumor detection, classification, segmentation, and prognosis prediction. Unlike traditional two-dimensional CNNs, 3D CNNs can effectively analyze volumetric medical imaging data, improving spatial feature extraction and diagnostic accuracy across imaging modalities such as CT, MRI, PET, and ultrasound. This systematic review and meta-analysis evaluates the diagnostic capabilities and clinical utility of 3D CNNs across 22 studies, including 11 eligible for quantitative synthesis. The pooled sensitivity, specificity, and AUC-ROC were 0.72, 0.73, and 0.77 respectively, with a diagnostic odds ratio (DOR) of 10.38, indicating favorable discriminative performance. Subgroup analyses revealed superior accuracy in lung cancer and CT-based models, with DenseNet and ResNet architectures outperforming traditional CNNs. Technical innovations including multi-modal fusion, spatial context integration, and explainable AI techniques enhance model robustness and clinical trust. However, high heterogeneity (I² > 95%) across studies, attributable to variations in imaging protocols, dataset quality, and model design, underscores the need for standardized methodologies. Limitations such as computational demands, annotation variability, and generalization challenges persist. Future directions emphasize the integration of explainable AI, PACS-compatible user interfaces, and federated learning frameworks to bridge institutional gaps. This review highlights the significant potential of 3D CNNs in advancing precision oncology, while also identifying the infrastructural and methodological refinements needed to enable widespread clinical adoption.

Post-HSCT COVID-19 Vaccination in Resource-Limited Settings: Why Adaptation Should Not Mean Compromise

Maryam Barkhordar — 2026-06-20

The Article Abstract is not available.

Severe Toxicodermia due to Apalutamide: A Case Report of DRESS in an Elderly Adult

Mónica Fernandes-Pineda — 2026-06-20

DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is a severe toxicoderma characterized by a hypersensitivity reaction to medications, accompanied by eosinophilia and systemic manifestations. Apalutamide, a selective androgen receptor inhibitor approved for the treatment of prostate cancer, has been associated with various dermatological complications. This study aims to document the clinical case of a geriatric patient with stage IV prostate cancer who developed toxicoderma after initiating treatment with apalutamide. An 81-year-old patient with a diagnosis of stage IV acinar adenocarcinoma of the prostate presented with a 15-day history of generalized papular lesions and general malaise, without improvement despite the use of oral antihistamines. The patient reported having started apalutamide four weeks prior.

Physical examination revealed facial edema and erythema, with erythematous and edematous plaques with a desquamative surface covering more than 50% of the body surface. Laboratory results showed eosinophils at 3040 cells/µL and a rise in baseline creatinine from 1.76 mg/dL to 2.4 mg/dL. The RegiSCAR score was 3 points, classifying it as a possible case of DRESS. A skin biopsy revealed a dermoepidermal hypersensitivity reaction with eosinophilic infiltration. The patient improved with oral and topical corticosteroids and the discontinuation of apalutamide. The diagnosis of DRESS was confirmed, and the patient remains under follow-up by the Oncology service.Several medications have been associated with the development of DRESS syndrome. Early recognition allows for the suspension of the causative treatment, thus reducing patient morbidity and mortality. It also facilitates a timely change in oncological therapy in advanced stages, preventing the patient from being left without adequate cancer management.

CNS Tuberculoma in a Patient of Acute Lymphoblastic Leukemia: A Rare Case Report

Kaustav Ghosh — 2026-06-20

Patients with acute leukemia are immunocompromised and highly susceptible to infections. Central nervous system tuberculoma is a rare but serious complication in immunocompromised patients, particularly those undergoing treatment for hematological malignancies. Early diagnosis is often challenging due to non-specific symptoms. We report the case of a 28-year-old female recently diagnosed with CALLA-positive B-cell Acute Lymphoblastic Leukemia, who presented with a two-month history of low-grade fever. Induction chemotherapy was initiated, but during the third week of treatment, she developed new-onset seizures. A Computed Tomography scan of the brain revealed a heterogeneous ring-enhancing lesion in the right parietal lobe. Magnetic Resonance Imaging with MR spectroscopy demonstrated characteristic lipid peaks, supporting the diagnosis of a tuberculoma. Antitubercular therapy including rifampicin, isoniazid, pyrazinamide, ethambutol, along with pyridoxine and dexamethasone, was commenced. The patient showed a favourable response, with resolution of fever and no recurrence of seizures. This case underscores the importance of considering CNS tuberculosis in the differential diagnosis of unexplained neurological symptoms and fever in patients with acute leukemia, particularly in regions where tuberculosis is endemic. Prompt diagnosis and treatment can lead to favourable outcomes.