Iraqi Journal of Hematology

Abstract:
Hemophilia, a genetic disorder characterized by impaired blood clotting, often leads to joint and muscle bleeds, resulting in chronic pain and reduced mobility. Exercise has emerged as a therapeutic intervention to enhance physical capacity and minimize bleeding risks among individuals with hemophilia. The aim of the present scoping review to explore and synthesize the available literature on exercise prescription in hemophilia, focusing on its role in promoting mobility and reducing bleeding complications. A systematic search was conducted across multiple databases, following the Preferred Reporting Items for Systematic reviews and Meta‑analyses extension for Scoping Reviews guidelines to identify studies addressing types, intensity, frequency, and safety measures associated with exercise in hemophilia management. Our findings highlight various exercise protocols, including resistance training, aquatic exercises, and low‑impact aerobic activities, as effective in improving joint stability, muscle strength, and overall physical function. The review also identifies critical safety considerations, such as personalized exercise intensity and regular monitoring to prevent injury. Although evidence supports the benefits of structured exercise, there remains a need for standardized guidelines specific to hemophilia. Future research should focus on long‑term outcomes and individualized exercise regimens to optimize therapeutic gains. This review offers a foundation for healthcare professionals to develop tailored exercise prescriptions, facilitating better mobility, and reduced bleeding risk in hemophilia patients.

BACKGROUND: Chronic myeloid leukemia (CML), a myeloproliferative neoplasm caused by genetic abnormality resulted in BCR‑ABL1 fusion gene, leading to constitutive tyrosine kinase activity. Despite improved treatment outcomes of tyrosine kinase inhibitors (TKIs), resistance to these agents due to mutations in targeted BCR‑ABL gene is still a challenge. Bosutinib is consider one of TKI, it inhibit both Sarcoma kinase and Ablson kinase (SRC/ABL), It is approved for patients for whom frontline TKIs is failed or undergo adverse effects.
OBJECTIVE: This study aims to evaluate the efficacy of bosutinib as a second‑line treatment for CML patients who have previously failed or experienced intolerance to other TKIs.
MATERIALS AND METHODS: A cross‑sectional study was conducted from October 2021 to December 2023 at the National Center of Hematology. Thirty CML patients were enrolled, all of whom had received bosutinib following failure or intolerance to prior TKI treatments (imatinib and/or nilotinib). Data collected included patient demographics, prior treatment history, and laboratory results. BCR‑ABL levels were quantitatively measured using polymerase chain reaction at baseline and 6 months posttreatment. Statistical analyses included paired t‑tests and correlation assessments.
RESULTS: The study included 30 CML patients (12 males and 18 females) with a median age of 49.5 years. Most patients (60%) had received imatinib only prior to bosutinib. A significant decrease in mean BCR‑ABL levels was observed after 6 months of bosutinib treatment (P < 0.0001), with 53% of patients achieving optimal molecular response as per the European LeukemiaNet criteria. Correlation analyses indicated significant relationships between BCR‑ABL level and white blood cell count (P = 0.006) and between treatment duration and hemoglobin level (P = 0.001). In addition, patients previously treated solely with imatinib responded to bosutinib significantly better than those who had received both imatinib and nilotinib (P = 0.0272).
CONCLUSION: Bosutinib demonstrated significant efficacy as a second‑line treatment for CML in patients who showed failure response to prior TKI therapies. These findings support bosutinib usage in managing CML, particularly in patients with a history of single TKI treatment, and underscore the necessity for ongoing research into resistance mechanisms and alternative therapies.

Abstract:
Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon acquired complement‑mediated hemolytic anemia characterized by continuous destruction of red blood cells leading to dark red or black colored urine. A 42‑year‑old man has been experiencing recurring jaundice, gastrointestinal discomfort, and high‑colored urine for the past 2 years. His hemogram and antiglobulin tests were normal. The hemolytic anemia workup revealed reticulocytosis, hemoglobinuria, urine hemosiderin, elevated indirect bilirubinemia, and extremely low haptoglobin. A high index of suspicion for PNH prompted the laboratory physician to do flow cytometry, which confirmed the diagnosis of classical PNH. Here, we discuss a case of PNH that remained undiagnosed for years, detailing how we successfully identified a rare and confusing case of hemolytic anemia without cytopenia.

Abstract:
Graft-versus-host disease (GVHD) remains a critical obstacle in the success of allogeneic hematopoietic stem cell transplantation (HSCT), adversely affecting patient survival and posttransplant quality of life. Recent advancements in GVHD prophylaxis emphasize achieving a delicate equilibrium between effective immunosuppression and preservation of the graft-versus-tumor (GVT) effect. This article synthesizes cutting-edge developments, including immune modulation strategies such as regulatory T-cell expansion and cytokine blockade, novel pharmacological approaches like Janus kinase inhibitors and posttransplant cyclophosphamide, and cellular therapies leveraging mesenchymal stromal cells and ex vivo-expanded regulatory T cells. Furthermore, the advent of biomarkers such as ST2 and microRNA signatures has enabled early risk stratification, fostering personalized, risk-adapted prophylactic strategies. By integrating these innovations, HSCT outcomes can be significantly improved, offering enhanced safety, reduced GVHD incidence, and optimized long-term patient care.

Abstract:
The incidence of anemia in Africa is still of major epidemiological significance. This study aims to determine the prevalence of anemia in Africa through a systematic review and meta‑analysis of the published studies. We conducted a comprehensive search across five electronic databases (Web of Science, PubMed, ScienceDirect, Scopus, and Google Scholar) using specific keywords to address the prevalence of anemia following the Preferred Reporting Items for Systematic Reviews and Meta‑analyses guidelines. A meta‑analysis was performed on our eligible studies using the random‑effects model. Our search returned 101 eligible articles involving 79,572 anemia cases in 14 African nations. The overall pooled prevalence of anemia in Africa was 29.2% (95% confidence interval: 25.2%–33.7% I2 = 99.28%). Subgroup analyses revealed variations in the prevalence across different countries, study designs, maturity status of participants, and publication years. Notably, Egypt and South Africa exhibited high prevalence rates of 99.5% and 85.6%, respectively, whereas Ethiopia reported a moderately low prevalence of 19.3%. The maturity status also influenced prevalence rates, with children indicating a higher prevalence (58.8%) compared to adults (21%). The study highlights the significant burden of anemia in Africa; the findings underscore the need for targeted public health interventions and improved standard of living to manage and control anemia in the region.

BACKGROUND: The advent of tyrosine kinase inhibitors (TKIs) has significantly improved the survival rates of patients with chronic myeloid leukemia (CML) patients. The frequent side effects of TKIs have necessitated the need for a new approach. Treatment‑free remission (TFR) has become a key goal in CML management, allowing eligible patients who meet specific criteria to safely discontinue TKI therapy.
OBJECTIVES: The objectives of this study were to identify CML patients on TKI therapy who are eligible for TFR, compare the clinical and hematological parameters among eligible and ineligible patients, and explore the reasons for patients’ willingness or reluctance to pursue TFR.
PATIENTS AND METHODS: This retrospective study reviewed 129 accessible medical records of CML patients in three hemato‑oncology centers in Iraqi Kurdistan between 2008 and 2024. Eligibility for TFR was assessed based on local criteria aligned with international guidelines, and eligible patients were compared to ineligible ones.
RESULTS: Files of 129 CML patients on TKI therapy were reviewed. Their median age at diagnosis was 46 years. Only 8.5% of the patients were eligible for TFR. Ineligibility was primarily due to insufficient TKI treatment (41.6%), inadequate deep molecular response (17.5%), and lack of regular molecular follow‑up (40.6%). While patients expressed their desire to discontinue TKI to avoid side effects and reduce compliance, reluctance stemmed from fear of relapse and the unavailability of newer generation TKIs in case of the development of resistant mutations.
CONCLUSIONS: A minority of CML patients in our region were eligible for TFR. Ineligibility for TFR was mainly due to insufficient TKI therapy and irregular molecular monitoring.

BACKGROUND: Multiple myeloma (MM) is a hematological malignancy that affects the bone marrow (BM) and results from the multiplication and infiltration of malignant plasma cells into the BM. Osteopontin (OPN) regulates the processes of osteoclast differentiation, translocation, and activation. Furthermore, it has an important role in angiogenesis in MM.
OBJECTIVES: The objective of this study was to assess the association between plasma OPN level in MM patients with both the disease stage and bone involvement and to find the correlation of OPN level with laboratory parameters and glomerular filtration rate (GFR).
PATIENTS, MATERIALS, AND METHODS: Eighty individuals were enrolled in the study; 40 of them were patients diagnosed with de novo MM before starting any treatment and 40 were healthy individuals as a control group. Enzyme‑linked immunosorbent assay technique was utilized for measurement of the levels of OPN and β2‑microglobulin (β2M) in plasma.
RESULTS: The median plasma OPN level was significantly higher in MM patients compared to the control group (P < 0.001). Plasma OPN level was significantly correlated with serum uric acid (P = 0.029), GFR (P = 0.001), and β2M (P < 0.001). Patients in Stage III had higher OPN level than those in Stages I and II (P < 0.001). Patients with lytic bone lesions and/or pathological fractures had significantly higher OPN than patients with osteoporosis alone or no bone lesion (P = 0.029).
CONCLUSIONS: Plasma OPN can be considered a prognostic parameter in evaluating patients with MM, given its significant elevation in Stage III, and a predictor of the severity of bone disease and renal insufficiency.

Abstract:
BACKGROUND: Smoking and vaping tobacco present substantial health hazards. Nevertheless, the precise impact of vaping and cigarette smoking on hematological indicators, such as complete blood count (CBC) and erythrocyte sedimentation rate (ESR), is still uncertain.
OBJECTIVES: This study was conducted to examine the impacts of vaping and smoking on hematological parameters on young, physically fit male university students.
MATERIALS AND METHODS: A cross‑sectional study was carried out that included 102 male students from Komar University of Science and Technology. The study was conducted between February and June 2024. Standard techniques were employed to collect and analyze blood samples for CBC and ESR.
RESULTS: Out of the 102 participants, with an average age of 21 years, 71 were smokers and 31 were nonsmokers. Smokers exhibited significantly higher red blood cell (RBC) count, hemoglobin (HGB) levels, and hematocrit (HCT) compared to nonsmokers. The platelet count was lower in smokers in compare to nonsmokers. On the other hand, vapers demonstrated the highest RBC count among the subgroups, followed by those who smoked both cigarettes and vapes. Furthermore, there were no notable disparities detected in ESR and other CBC values between the participant groups.
CONCLUSIONS: The study revealed that smoking significantly elevates RBC count, HGB, and HCT levels while reducing platelet counts. Among vapers, RBC levels were highest, but no significant differences were observed in platelet counts nor ESR. Therefore, smoking and vaping have an impact on the characteristics of RBCs; this signifies that additional research is required to investigate the long‑term impacts of smoking and vaping on hematological parameters.

Abstract:
BACKGROUND: Deep learning’s role in blood film screening is expanding, with recent advancements including algorithms for the automated detection of sickle cell anemia, malaria, and leukemia using smartphone images.
OBJECTIVES: This study aims to build the artificial intelligence (AI) models and assess their performance in classifying blood film cells as normal or abnormal.
MATERIALS AND METHODS: The dataset included 171,374 images from 961 patients which were classified by experts. These images were resized, denoized, normalized, augmented, and classified into two categories, normal and abnormal cells. Two stain normalization techniques were used in this study; Reinhard and Mackenko techniques. The data were split into training and testing sets with a ratio of (8:2). The model was built through transfer learning by using the pretrained model Inception‑Resnet v2 as a backbone. Three different fine‑tuning techniques were tested in this study. The training was done using Python with Keras library on Google Colab for 10 epochs. The model was tested for accurately classifying individual blood cells whether normal or abnormal and evaluated using accuracy and area under receiver operator characteristic curve.
RESULTS: The counts of the three most common cell types were as follows: Segmented neutrophils: 29,424; erythroblasts: 27,395; and lymphocytes: 26,242. The Reinhard stain normalization had better accuracy than Mackenko, the best AI model achieved the highest accuracy of 96.7%%, the area under the curve (AUC) of 99.87%, while the second technique achieved an accuracy of 91.46% and an AUC of 97.23% in classifying normal from abnormal cells.
CONCLUSION: In conclusion, AI can effectively classify the blood cells as either normal or abnormal, yielding accurate results in a time‑effective manner, especially with the use of transfer learning of pretrained models and fine‑tuning. In this study, Inception‑Resnet V2 showed good accuracy in differentiating normal from abnormal cells.

Abstract:
BACKGROUND: Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome (BCR-ABL1 fusion gene). CML primarily progresses through chronic, accelerated, and blast phases. While global studies on BCR-ABL1 fusion transcript types and their associations with clinical, laboratory, and prognostic profiles exist, such data is scarce in Malaysia.
OBJECTIVES: This study aimed to determine the distribution of BCR-ABL1 fusion transcript types and evaluate their associations with demographic, clinical, laboratory, prognostic profiles, and disease outcomes among Malaysian CML patients.
PATIENTS, MATERIALS AND METHODS: A total of 98 patients diagnosed with CML were identified at East Coast Hospital, Malaysia. This 12‑year cross‑sectional study was carried out using data extracted from patients’ medical records. Molecular results for BCR‑ABL1 fusion genes were obtained using one‑step multiplex reverse transcriptase polymerase chain reaction.
RESULTS: Out of the 98 patients, 56% had e14a2, 41% had e13a2 fusion transcripts, while the remaining 2 patients had e14a3 transcripts. Additionally, 1 patient co‑expressed both e13a2 and e14a2. Among patients with the major BCR‑ABL1 transcript type, those with e14a2 fusion transcripts showed an older median age (P = 0.025), while patients with e13a2 fusion transcripts had significantly higher white blood cell (WBC) counts (P = 0.014). Furthermore, there were significantly more patients with blastic transformation in the e13a2 group (P = 0.038). The median latency period of CML was 12 months. The blast cell lineages consisted of myeloid (68.4%), followed by B‑lymphoid (26.3%) and mixed phenotypic (5.3%). The differences in fusion transcript expression might influence certain parameters; for instance, older patients were associated with the e14a2 fusion transcript. Meanwhile, patients exhibiting e13a2 might have a higher WBC count at diagnosis and be more vulnerable to blastic transformation of CML.
CONCLUSIONS: This study highlights the predominance of e14a2 fusion transcripts in Malaysian CML patients and its association with older age. The e13a2 transcript was linked to higher tumor burden and a higher rate of blastic transformation, suggesting potential prognostic significance. These findings underscore the importance of baseline molecular profiling for optimizing disease management.

Abstract:
BACKGROUND: Chronic lymphocytic leukemia (CLL) is not an uncommon hematological malignancy which affects elderly individuals primarily. It is more common in developed world. Interleukin‑6 (IL‑6) is a soluble mediator with a pleiotropic effect on inflammation, immune response, and hematopoiesis. Due to its major role in initiation as well as resolving inflammation, deregulation of IL‑6 is a mainstay of chronic inflammatory and autoimmune diseases. In addition, IL‑6 has been shown to be implicated in the pathogenesis of many human malignancies.
OBJECTIVES: The aim of the study was to measure the plasma level of IL‑6 in newly diagnosed pretreated CLL patients and its association with disease stage and peripheral blood indices.
PATIENTS, MATERIALS AND METHODS: A case–control study included 60 patients who are newly diagnosed untreated CLL patients classified into three stages according to the Binet classification system as a patient group and 20 healthy individuals as a control group. The samples were collected from the patients during their attendance at the laboratories of the Hematology Center of the Medical City in Baghdad. For the determination of plasma level of IL‑6 in both patient and control groups, an ELISA‑based method was used.
RESULTS: IL‑6 plasma level was higher significantly in the patient’s group than in the control group (P < 0.001), with the highest IL‑6 level found in Stage C and the least IL‑6 level found in Stage A (P = 0.043). The white blood cell count shows a high correlation to IL‑6 level when compared to other peripheral blood elements (hemoglobin and platelet count) but is still not statistically significant. Regarding age and gender, they did not have a statistical significance (r = 0.081, P > 0.05) on the mean plasma level of IL‑6 within both the patient and control group.
CONCLUSIONS: In this study, IL‑6 plasma levels are significantly correlated with the stage of the disease as its level is the highest in CLL patients with advanced disease. IL‑6 is an independent prognostic factor in the prediction of the activity and the stage of the disease in these patients.

Abstract:
BACKGROUND: Defects in the production of one or more hemoglobin chains result in a set of hereditary hematologic illnesses known as thalassemias. Alpha and β‑thalassemia are the two primary thalassemia classifications. The pathophysiology of β‑thalassemia is significantly influenced by endothelial activation markers, such as vascular cell adhesion molecule 1 (VCAM‑1), which have been found to be higher in both transfusion‑dependent and nontransfusion‑dependent thalassemia patients. These markers have been suggested for the follow‑up of vascular disease in this patient group.
OBJECTIVES: The aim of this study was to evaluate the level of soluble VCAM‑1 in β‑thalassemia major patients and to correlate its level with the clinical parameters.
PATIENTS, MATERIALS AND METHODS: This case–control study was enrolled on 40 patients with β‑thalassemia major. They were collected from Thalassemia Center of Babylon Maternity and Pediatrics Teaching Hospital, from December 28, 2022, to March 30, 2023. Twenty of them were splenectomized, others were not. Another 40 apparently healthy individuals with no family history of thalassemia or other hemoglobinopathy were enrolled in this study as controls. The samples were collected to assay the human VCAM‑1 using enzyme‑linked immunosorbent assay based on the biotin double antibody sandwich technology.
RESULTS: Among 80 subjects, age and body mass index were similar across groups. There are differences in complete blood count (CBC) parameters between thalassemic and control groups. Thalassemic patients displayed notably higher levels of VCAM‑1 and ferritin compared to controls and in splenectomized patients than nonsplenectomized patients. There is a high significant correlation exists between VCAM‑1 and ferritin, VCAM‑1 and various CBC parameters.
CONCLUSIONS: There are higher levels of VCAM‑1 in β‑thalassemia major patients compared to the control and in splenectomized compared to non-splenectomized patients which usually associated with disease complications, furthermore it reflect endothelial activation and dysfunction.

Abstract:
BACKGROUND: Chronic myeloid leukemia (CML) is a type of cancer that originates in hematopoietic stem cells, particularly those that develop into myeloid cells. A key feature of CML is the Philadelphia (Ph) chromosome, which is produced by a reciprocal translocation between chromosome 9 and chromosome 22 (designated as t [9;22]). This chromosomal change results in the creation of the BCR‑ABL1 fusion gene. Several genetic association studies have analyzed the link between the catalase (CAT) C262T variant and different cancers, but the findings remain controversial.
OBJECTIVE: This study was aimed to determine the association between CAT‑21A\\\\T (rs 7943316) gene polymorphism and the percentage of human herps virus‑7 (HHV‑7) in patients with CML.
PATIENTS AND METHODS: A case–control study included 120 CML blood specimens enrolled in the current research, including 40 newly diagnosed CML patients and 80 treated CML patients, as well as 50 blood specimens collected from persons as the control group. Sequencing was used to identify the CAT‑21A\\\\T (rs 7943316) gene polymorphism and HHV‑7 DNA using conventional polymerase chain reaction (PCR).
RESULTS: The current study included 40 newly diagnosed CML patients with a mean age of 48 ± 12.7 years and 80 treated CML patients with a mean age of 50 ± 10.53 years, whereas the mean age of the 50 controls was 50 ± 12.95 years. PCR testing for HHV‑7 revealed positive results in 6 (15%) of newly diagnosed CML patients and in 19 (23.8%) of those treated for CML. In contrast, one person in the control group was infected by HHV‑7. The difference in frequency of genotype distribution of the polymorphism between newly diagnosed, treated patients with CML and control groups was statistically significant. There was no correlation between CAT‑21A\\\\T (rs 7943316) polymorphism and HHV‑7 infection. New recording for CAT‑21A\\\\T (rs 7943316) polymorphism in gene bank NCBI and American bank.
CONCLUSION: HHV‑7 acts as a cofactor in pathogenesis as well as the development biology of CML in Iraqi patients. Polymorphism of CAT‑21A\\\\T (rs 7943316) may play a role as a risky factor in the pathogenesis of idiopathic CML.

Abstract:
BACKGROUND: With a high degree of intratumoral and interpatient heterogeneity, chronic lymphocytic leukemia (CLL) is a malignant lymphoproliferative illness characterized by the accumulation of defective B lymphocytes in the blood and lymphoid tissues. A multifunctional glycoprotein released by the body, progranulin (PGRN) is linked to inflammation, repair, development, and carcinogenesis. As a prognostic indicator, PGRN was discovered to be elevated in a large number of solid tumors and a small number of hematological malignancies.
OBJECTIVES: The objective of the study was to assess the plasma PGRN level in newly diagnosed CLL patients in comparison to healthy controls and to establish a correlation between it with plasma beta‑2 microglobulin (β2M), hematological parameters, and disease stage.
PATIENTS, MATERIALS, AND METHODS: From October 1, 2022, to March 1, 2023, 50 newly diagnosed CLL patients visited the Baghdad Teaching Hospital on the Medical City campus. This cross‑sectional study was conducted. The diagnosis was made using immunophenotyping by flow cytometry and morphology, with a control group of 30 healthy people. PGRN and β2M plasma levels were assessed using an enzyme‑linked immunosorbent assay.
RESULTS: A (P = 0.001) indicated a statistically significant difference in plasma PGRN level between the patients’ median of 5.62 ng/mL and the control groups’ median of 2.37 ng/mL. The Binet staging system revealed that there was a significant difference with regard to absolute lymphocyte count, smudge cell percentage, and plasma β2M (P = 0.01, 0.001, 0.049), respectively, but there was no statistically significant difference between the stages with regard to age and plasma PGRN level (P = 0.35, 0.9). With a P = 0.046, PGRN demonstrated a strong positive correlation with β2M.
CONCLUSIONS: Compared to healthy controls, patients with CLL showed higher levels of PGRN. The other poor prognostic sign, β2M, and the high PGRN levels at baseline correlate well; however, no difference was found when comparing the levels at later stages of the disease.

Abstract:
BACKGROUND: Thalassemia is potentially inherited fatal anemia and can cause health problems when left untreated. Beta‑thalassemia is the most severe formula of the illness. Transforming growth factor‑beta (TGF‑β) is a cytokine that has multicellular functions. The miRNAs have been confirmed to play important roles in gene expression regulation during the development of a variety of human diseases. In a variety of hematological diseases, miRNAs influence the TGF‑β signaling pathway. The etiology of the disease may be supported by the dysregulation of this interaction.
OBJECTIVES: This study aimed to estimate the role of TGF‑β and its target miR‑1908‑5p expression and its effect on the prognosis and treatment of beta‑thalassemia (β‑thal) in Iraqi patients.
PATIENTS, MATERIALS, AND METHODS: The case–control study encompassed 100 Iraqi individuals, categorized into two groups: Fifty patients diagnosed with β‑thal and fifty apparently healthy controls. Blood samples were collected from Baghdad Teaching Hospital at the Medical City in Baghdad from December 2023 to February 2024. Hematological and biochemical parameters were measured. Total RNA was extracted and converted into complementary DNA, finally, to assess the levels of TGF‑β and miR‑1908‑5p gene expression by the reverse transcription‑polymerase chain reaction.
RESULTS: The results showed that a decrease in the hemoglobin (Hb) level was significantly correlated with a significant increase in the ferritin level and the white blood cell (WBC) count in thalassemia patients in comparison to healthy controls, with a significant difference (P < 0.01). The expression of the TGF‑β gene was notably lower in thalassemia patients (0.783) compared with control, with an increase in the miR‑1908‑5p gene expression level (1.431); furthermore, the correlation between them using Spearman’s coefficient was negative with a significant difference of 0.04.
CONCLUSION: A low level of Hb in patients acts as a pointer to increase the level of the ferritin and the WBC count. A low level of gene expression of the TGF‑β gene targeted by high‑level miR‑1908‑5p gene expression in Iraqi patients with β‑thal is considered a good biomarker according to the ROC curve test. It might be possible to regulate TGF‑β expression by modifying miR‑1908‑5p, therefore could improve the effectiveness of gene‑based therapies in hematological therapies

Abstract:
BACKGROUND: Beta thalassemia major is a hereditary blood disorder characterized by defective hemoglobin production, leading to severe anemia and multiple complications. Among these, reproductive dysfunction is a significant concern for affected females, often linked to iron overload from frequent blood transfusions. The hepcidin antimicrobial peptide (HAMP) gene, a key regulator of iron homeostasis, may play a crucial role in this context. Variations in the HAMP gene could influence iron metabolism and, consequently, impact the secretion and regulation of fertility hormones. Understanding this relationship could provide insights into managing fertility issues and enhancing the quality of life for these patients.
OBJECTIVES: This study aims to investigate the effect of HAMP gene polymorphism on fertility hormones in female patients with beta‑thalassemia major.
PATIENTS, MATERIALS AND METHODS: A cross‑sectional case–control study was conducted over a period of 6 months from January to June 2024 involving 180 women (90 healthy control and 90 patients) aged 16–40 years. Patients were randomly selected according to the specific inclusion and exclusion criteria. The HAMP gene polymorphism was determined by polymerase chain reaction – restriction fragment length polymorphism, and the serum level of hepcidin hormone, ferritin, and fertility hormones were measured by Enzyme‑Linked Immunosorbent Assay. SPSS Program was used to code, enter, and process the gathered data.
RESULTS: The genetic analysis of HAMP gene (c.582A>G, rs10421768) revealed significant differences in genotype polymorphisms between patients and controls. Patients with GG genotype had the lowest hepcidin levels (P = 0.001). AG genotype was associated with the highest ferritin levels. Fertility hormone levels were lower in GG versus AG and AA genotypes.
CONCLUSIONS: HAMP gene polymorphisms are associated with reduced hepcidin levels, increased iron overload, and altered fertility hormones in females with beta‑thalassemia major, suggesting a genetic contribution to iron dysregulation and endocrine dysfunction in these patients.

Abstract:
BACKGROUND: Hemophilia and other hereditary bleeding disorders patients who received blood and blood product transfusions are particularly vulnerable to viral infection including risk of transmission of parvovirus B19, which remains a critical issue.
OBJECTIVES: The aim of this study was to screen Parvovirus B19 infection in hereditary bleeding disorders patients.
PATIENTS, MATERIALS, AND METHODS: Sixty‑one patients diagnosed with hemophilia and other hereditary bleeding disorders were recruited in this study. Out of 61 patients, 73.77% had hemophilia A, 13.11% had hemophilia B, 6.56% had von Willebrand disease, and 6.56% had congenital factor VII deficiency. Patients’ clinical data were collected and evaluated during their follow‑up visits. The presence of inhibitors in patients with hemophilia A was also recorded. Detection of parvovirus B19 DNA was performed using nested polymerase chain reaction protocol, and immunoglobulin G (IgG) detection was done using the enzyme‑linked immunosorbent assay technique. Statistical analysis was performed using GraphPad Prism software (v7.0).
RESULTS: Despite the lack of significance, more than half (55.74%) of different types of hereditary bleeding disorders (34 patients) were seropositive for Parvo B19 IgG antibodies, while all patients had negative parvovirus B19 DNA. Additionally, 15 (33.33%) patients with hemophilia A had inhibitors to factor VIII, without increased association among those patients with positive IgG antibodies (P > 0.9999). Furthermore, the prevalence of hepatitis C virus and hepatitis B virus among all studied patients was 33 (54.1%) and 3 (4.92%), respectively, without signification association with a positive serological test of Parvo B19 virus (P = 0.0621 and P = 0.6959, respectively).
CONCLUSIONS: This study revealed that most patients had past exposure to Parvovirus B19, as indicated by IgG seropositivity, while the absence of detectable viral DNA suggests no current infections which underscore the likelihood of past transmission via blood or blood derived products. Therefore Regular monitoring of viral infections in hereditary bleeding disorder patients are crucial for improving infection control measures.

Abstract:
BACKGROUND: Sickle cell disease (SCD) is a heterogeneous disease which can induce fatal complications, especially cardiovascular complications. The development of a classification system to classify patients with SCD helps to identify those with high risk for further preventive measures and follow‑up.
OBJECTIVES: This study evaluates the relationship between SCD severity and the risk of pulmonary hypertension (PH) development aiming to identify the group of SCD patients who are at high risk of PH development for further preventive measures.
PATIENTS AND METHODS: Retrospective analysis for SCD patients retrieved from records from 2009 to 2021. Five hundred and seventeen patients were selected; all patients were assessed for the risk of PH by following the guidelines of the European Society of Respiratory and European Society of Cardiology using echocardiography. Patients were then classified according to the Severity Classification System for SCD into three classes from the least severe to the most severe. This study was held at King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
RESULTS: Among participants, 93% have a low risk of PH. Fifty‑eight (11.2%) patients have a severe SCD, and 458 (88.5%) patients have mild SCD. Twenty‑nine (80.5%) of individuals with SCD who have a high or moderate risk of PH were found to have severe SCD (Class III).
CONCLUSION: SCD severity is strongly correlated with the risk of PH development. The severity classification system is easily applicable to identify those with a high risk of PH development to apply further preventive strategies.

Abstract:
Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon acquired complement‑mediated hemolytic anemia characterized by continuous destruction of red blood cells leading to dark red or black colored urine. A 42‑year‑old man has been experiencing recurring jaundice, gastrointestinal discomfort, and high‑colored urine for the past 2 years. His hemogram and antiglobulin tests were normal. The hemolytic anemia workup revealed reticulocytosis, hemoglobinuria, urine hemosiderin, elevated indirect bilirubinemia, and extremely low haptoglobin. A high index of suspicion for PNH prompted the laboratory physician to do flow cytometry, which confirmed the diagnosis of classical PNH. Here, we discuss a case of PNH that remained undiagnosed for years, detailing how we successfully identified a rare and confusing case of hemolytic anemia without cytopenia.

Abstract:
Using single‑agent high‑dose melphalan for multiple myeloma and refractory or relapsed (R/R) lymphomas transplant was reported to be clinically beneficial. In view of earlier literature, we opted for this new, modified conditioning regimen (carmustine and melphalan instead of BEAM; B – Carmustine, E – Etoposide, A– Cytarabine, and M– Melphalan) in our patient for autologous hematopoietic stem cell transplantation (aHSCT) to treat relapsed/refractory gastric diffuse large B‑cell lymphomas (DLBCLs) in resource‑limiting counties like India. In this report, we have articulated all our clinical experiences and insights related to our patient pre‑ and post‑aHSCT in terms of treatment outcomes and survival. Here, we report a case of a 63‑year‑old male diagnosed with gastric DLBCL and no history of smoking, alcohol, or use of illicit drugs. Routine positron emission tomography–computed tomography (PET‑CT) revealed abnormally increased fluorodeoxyglucose (FDG) uptake in parts of the stomach (maximum standardized uptake value: 51.2). Immunohistochemistry revealed high‑grade non‑Hodgkin’s lymphoma of B‑cell phenotype (DLBCL of stomach). The patient was started on 6 cycles of R‑CHOP (R – Rituximab, C – Cyclophosphamide, H – Doxorubicin, O – Vincristine, P – Prednisone) regimen. End‑of‑treatment FDG PET‑CT revealed persistent disease. Hence, the patient received radiation therapy (involved‑field radiotherapy‑45 Gy/25#). Later, the patient was planned for salvage chemotherapy followed by aHSCT. It’s been > 18 months’ post‑aHSCT, the patient is event‑free and is on a 6‑monthly follow‑up.

BACKGROUND: Red cell distribution width (RDW) is one of the red cell parameters. It reflects the variation in the size and shape of red blood cells (RBCs). It changes in different disease processes. It has a role in evaluating the prognosis in patients with different cancer types, including hematological malignancies, reflecting the effect of inflammatory cytokines produced by malignant cells on the shape and size of RBC. In general, cancer‑associated inflammation represents the hallmark of cancer development and progression. Based on these facts, many studies evaluate the role of RDW in the prognosis. RDW is associated with cancer‑induced malnutrition and malabsorption, which causes hematinic deficiency, reflecting its correlation with poor prognosis. Furthermore, higher RDW is associated with higher cardiovascular and inflammatory risks, thus increasing the risk of chemotherapy‑induced cardiotoxicity.
OBJECTIVES: We assess the difference between RDW from healthy people and patients diagnosed with hematological malignancies.
MATERIALS AND METHODS: This study was performed in Babylon Province, comparing the RDW difference between healthy people and hematological malignancy patients. A total of 148 participants, 74 of them were healthy people and 74 were newly diagnosed with hematological malignancies, 44 with myeloid malignancy, 30 with lymphoid malignancy.
RESULTS: The mean RDW‑coefficient of variation (CV) for healthy people was 13.33 ± 1.14, whereas that for patients was 16.12 ± 3.62 with a significant difference (P < 0.0001). Similarly, the mean RDW‑standard deviation (SD) for healthy people was 45.01 ± 4.96, whereas that for patients was 57.10 ± 12.78 with a significant difference (P < 0.0001). Similarly, there is a significant difference in RDW‑SD and RDW‑CV between those with myeloid and lymphoid neoplasms as separately compared to healthy people (P < 0.0001). However, a significant difference was only found in RDW‑CV in comparison between these two groups (P = 0.04).
CONCLUSION: Measurement of RDW of both types is important for predicting the prognosis of hematological malignancies. However, it is limited to the determination of the significant difference in RDW between healthy people and patients who are newly diagnosed with hematological malignancies without studying RDW effect on disease prognosis.

BACKGROUND: Blood transfusion therapy is the main therapy for thalassemia patients. Active reporting of acute reactions during blood transfusions can play a pivotal role in the prevention of under‑reporting of these events.
OBJECTIVE: The objective of the study was to evaluate the true incidence of acute transfusion reactions in pediatric thalassemia patients using active surveillance in comparison with the data obtained from passive reporting for the same duration of time.
MATERIALS AND METHODS: This cross‑sectional cohort study comprised both prospective (active surveillance) and retrospective (passive reporting) components, including 248 and 292 thalassemia patients, respectively, aged 1–16 years, who underwent regular blood transfusions. Information collected included patient demographics and details of present and previous transfusion reactions. The data were analyzed using IBM‑SPSS Statistics 16.0.
RESULTS: A total of 300 transfusion episodes were directly observed among 248 thalassemia patients, all receiving red blood cell concentrates. During 4 months of active surveillance, the incidence of acute transfusion reactions was 6.3% (19 out of 300), including 11 (3.7%) febrile nonhemolytic transfusion reactions (FNHTRs) and eight urticarial reactions (2.6%). In the retrospective data from passive reporting, 320 transfusion episodes occurred among 292 patients, with only 2 reactions (0.62%), FNHTRs and acute hemolytic transfusion reactions reported.
CONCLUSION: Active surveillance revealed a significant difference between the acute reactions identified during active surveillance in comparison with the data obtained from passive reporting for the same duration of time in pediatric thalassemia patients. In this regard, increased awareness related to transfusion reactions and importance of their reporting will be helpful to design a preventive framework for patients’ safety.