Iraqi Journal of Hematology

Abstract:
Acute lymphocytic leukemia (ALL) is a diverse category of hematological malignancies defined by the clonal proliferation of immature lymphoid cells. While advances in diagnostic procedures and treatment modalities have improved results for many patients, a group of them exhibit clinical characteristics that indicate a high risk of disease progression and unfavorable consequences. Understanding the underlying molecular processes and developing accurate prognostic indicators in this high‑risk group is critical for personalized treatment approaches and better patient outcomes. Hematological markers, immunophenotyping profiles, and chromosomal defects in people who were clinically high risk (CHR) for ALL are discussed in this review. Alterations in hematological markers, such as elevated white blood cell counts, decreased hemoglobin levels, and thrombocytopenia, are indicative of the aggressive nature of high-risk ALL. Immunophenotyping investigations revealed abnormal expression patterns of lineage‑specific markers, indicating clonal proliferation and differentiation arrest. Furthermore, cytogenetic examination revealed frequent chromosomal defects, such as the Philadelphia chromosome and hyperdiploidy, which have been linked to a poor prognosis in ALL patients. The combination of hematological, immunophenotypic, and cytogenetic data gives a thorough knowledge of disease biology and assists in risk assessment for patients with CHR for ALL. The present review elucidates the intricate interaction of hematological, immunophenotypic, and cytogenetic abnormalities in persons at clinically high risk for ALL, emphasizing the importance of integrated diagnostic techniques to enhance patient outcomes and optimize treatment strategies.

Abstract:
The incidence of anemia in Somalia is of medical concerns, especially among neonates and pregnant women. Despite the available intervention of the government to provide iron‑based supplement, the associated morbidity of anemia in Somalia is still of medical relevance. This systematic review and meta‑analysis were conducted to provide detailed information on the prevalence of anemia in Somalia. A systematic search for articles describing the prevalence of anemia within Somalia was conducted following the Preferred Reporting Items for Systematic Reviews and Meta‑analysis guidelines. A meta‑analysis was performed on our eligible studies using the random effect model. Our search returned 13 eligible articles involving 3988 participants within Somalia. There was a relative high prevalence of anemia in Somalia in this study 39.7% (95% CI: 26.3–53.1; I2=99.26%, P≤ 0.001). A higher proportion of these cases was from pregnant women. Cross‑sectional study designs had more incidence of anemia 39.8% (95% CI: 29.0–51.7) than retrospective studies 29.2% (95% CI: 17.0–45.3) in this review. There was a variation in the distribution of anemia in relation to the publication years at P< 0.001. Evidence from this study reveals that there is a high prevalence of anemiain Somalia and effort toward strategic treatment should be prioritized.

Abstract:
BACKGROUND: Menorrhagia, or excessive menstrual bleeding, is a common symptom in women with inherited bleeding disorders; they are conditions where the blood ability to clot is impaired. Some of the common bleeding disorders include von Willebrand disease (VWD), clotting factor deficiencies, and platelet function disorders.
OBJECTIVE: To assess different types of inherited bleeding disorders in women with menorrhagia referred to the National Center of Hematology/Mustansiriyah University in Baghdad/Iraq.
PATIENTS AND METHODS: A prospective study was carried out on 193 women who had experienced menorrhagia for a duration of 3 years, from 2020 to 2023. These women sought consultation at the National Centre of Hematology/Mustansiriyah University. All participants were diagnosed through various laboratory tests, including complete blood count, blood film, blood group and Rh, bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen level, factor assay, von Willebrand factor antigen using ELISA technique, ristocetin cofactor, and platelet function test.
RESULTS: Out of the 193 women with menorrhagia who participated in this study, the majority of whom had an unidentified cause (36.3%), followed by VWD (30.1%) and platelet function disorders (21.2%). Other bleeding disorders ( thrombocytopenia and factors deficiencies) were 5.7% and 6.7%, respectively. Furthermore, the results showed that there was a significant difference in family history and consanguinity between patients with a hereditary bleeding disorder and nonhereditary bleeding disorder (P < 0.001).
CONCLUSIONS: Fifty eight percent of females with Menorrhagia in this study have inherited bleeding disorders(IBDs), VWD, and thrombasthenia account for 51.3% are the most common causes of inherit bleeding disorder (IBD). Consanguineous marriage should be discouraged in Iraqi society to reduce such inherited diseases.

Abstract:
BACKGROUND: Certain hematologic cancers, including Kaposi’s sarcoma (KS), have been associated with the pathogenicity of human herpesvirus‑8 (HHV‑8). HHV‑8’s involvement in acute leukemia patients is yet unclear, nevertheless. The diagnosis, categorization, and course of treatment for acute myelogenous leukemia, an aggressive heterogeneous hematologic malignancy, have changed dramatically in recent years.
OBJECTIVE: This study aims to investigate the pathogenicity role of HHV‑8 in patients with acute myeloid leukemia (AML) of a group of the Iraqi population.
MATERIALS AND METHODS: Case–control research has been carried out on 75 fresh blood samples recruited from the Mirjan Teaching Hospital in Al‑Hilla City. The studied blood samples were obtained from patients with AML enrolled in this study, whereas control groups in the current study included 75 fresh whole blood. The specimens were collected during the period from June 2023 to February 2024. Conventional polymerase chain reaction (PCR) was used to identify HHV‑8.
RESULTS: The results show that the mean age of the patients with AML (48.5 ± 10.23 years) was more than that of the apparently healthy control (46.26 ± 11.21 years). There was a nonsignificant difference between patients with AML and the control group. In addition, the male in this study group constituted 56% (42/75), whereas 44% (33/75) were female. Furthermore, the positive of viral genome extraction was found in 41.3% (31 out of 75 of the specimens with viral genome), whereas 59.7% (44/75) specimens did not contain viral genome. The PCR results showed that in the AML patient group, the rate of HHV‑8 infection was 35.4% (11 out of 31 cases).
CONCLUSION: Considering the relatively small numbers included in our results, the positive results lead to the idea that HHV‑8 works as a cofactor in the tumor biology of the AML subset under consideration and may have contributed to its development.

Abstract:
BACKGROUND: The prevalence of anemia in children under 5 years of age is a multifaceted issue influenced by various factors, leading to diverse findings across studies. This study aimed to assess the prevalence of anemia and its associated factors among children under 5 years of age living in internally displaced persons camps in the Dayniile district of Somalia.
MATERIALS AND METHODS: This cross‑sectional study was conducted between December 2022 and July 2023 in Mogadishu, Somalia. Blood samples from children under 5 years of age were checked for malaria and parasites, as well as for hemoglobin, erythrocytes, hematocrit, mean cell volume, and hematocrit. SPSS version 27.0.1 was used for data analysis, involving descriptive and inferential statistics. Fisher’s exact test examined anemia associations due to low expected counts.
RESULTS: The prevalence of anemia among children under 5 years old was 17.6%. Anemia severity varied from mild (8.4%) to moderate (8.7%) to severe (0.5%). No significant correlation was found between a child’s primary caregiver and anemia status nor between anemia and sex, age, maternal factors, or family income sources. However, the presence of income from other relatives was statistically significant (P = 0.046*), indicating that financial support from extended family members may reduce the incidence of severe anemia in young adults. Children with a history of malaria had notably higher rates of mild and moderate anemia (25.0% and 75.0%, respectively) than those without.
CONCLUSION: Our study, along with previous research, underscores the complexity of the prevalence of childhood anemia and its contributing factors. Addressing anemia in children from lower‑income families and urban areas requires tailored intervention. In addition, controlling malaria and promoting breastfeeding are essential strategies for reducing the prevalence of anemia in young children. Overall, a multifaceted approach considering socioeconomic, health, and dietary factors is crucial for the well‑being of children under 5 years old.

Abstract:
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life‑threatening syndrome of fever, cytopenia, and organomegaly resulting from immune activation and cytokine storm. The syndrome can occur as a primary/familial form mostly affecting infants and young children or as an acquired form secondary to an underlying pathology (infection, malignancy, and autoimmune disease) that may have an underlying genetic predisposition, including mutations or polymorphisms.
PATIENTS AND METHODS: This case–control study was conducted in Basra, Iraq. Thirty‑four pediatric and adult patients with peripheral cytopenia attributed to bone marrow (BM) hemophagocytosis enrolled with 34 healthy individuals (age and sex matched) included as a control group. Whole blood was tested for complete blood count and screened for the presence of mutations in the perforin gene by polymerase chain reaction amplification; in addition, serum samples were tested for soluble CD25, ferritin, and triglycerides (TGs).
RESULTS: The mean hemoglobin level and platelets count were significantly lower in HLH patients compared to the control group (P < 0.001), while there was no significant statistical difference regarding neutrophils count (P > 0.05). Soluble CD25 (s.IL‑2R) testing revealed inconsistent results; serum ferritin and TGs were significantly higher in HLH patients compared to the control group (P < 0.001). About nine cases were genetically proven to have primary HLH; all were infants under the age of 6 months. Perforin gene mutations were detected in 38.8% (n = 7) of tested subjects. The novel frameshift mutation of the perforin gene (c.218_224del) was identified in four cases. Fifteen different perforin gene polymorphisms were detected in both case and control groups. Six out of nine infants with primary HLH did not survive, while the remaining three cases underwent BM transplantation.
CONCLUSION: Early diagnosis of HLH is often challenging; this study should increase awareness of the prevalence of familial HLH among infants; such cases require early recognition and referral to hematopoietic stem cell transplantation.

Abstract:
BACKGROUND: Stem cell transplant recipients have an increase in various infections depending on the immunosuppression. The purpose is to explore the effect of the use of proflactıc intravenous immunoglobulin (IVIG) on transplant recıpıents.
OBJECTIVE: It was aimed to examine the effect of IVIG on allogeneic stem cell transplantation.
MATERIALS AND METHODS: In this study, sepsis status, infection focus causing sepsis, neutrophil and platelet engraftment time of patients the length of stay in the hospital at the time of the stem cell transplant, if the patient died, how many days after the transplant the event developed, and the data of the bone marrow transplant unit were reviewed retrospectively. One hundred and eleven patients who were given IVIG (400 mg/kg/week IVIG intravenous was given to the patients as a weekly prophylactic up to 100 days starting on the 7th day after transplantation) and 190 patients who did not receive IVIG were included in the study.
RESULTS: There was no statistically significant difference between the IVIG groups in terms of gender, diagnosis, donor characteristics, and event (P > 0.05). Sepsis was observed significantly less in patients who were given IVIG compared to patients who were not given IVIG (P < 0.001). While it was observed that IVIG did not have a significant effect on platelet engraftment and discharge times (P > 0.05), neutrophil engraftment time was significantly higher in patients given IVIG compared to patients not given IVIG (P < 0.009). It was observed that the use of IVIG in patients with sepsis did not have a positive effect on survival. (with sepsis hazard ratio [HR]: 3.890 P = 0.001, IVIG given HR: 3.244 P = 0.035).
CONCLUSION: It was observed that the use of IVIG in allogeneic stem cell transplantation was associated with a decrease in sepsis, but the use of IVIG did not have a positive effect on survival and could prolong neutrophil engraftment.

Abstract:
BACKGROUND: B-cells express a variety of clusters of differentiation markers during development. These markers determine the basic function of the immune phenotype specific to B-cells. Changes in the expression of these markers are linked to the development of many diseases, including chronic inflammation, autoimmune diseases, and immunodeficiency.
OBJECTIVE: The current study aimed to investigate a change in CD24, CD27, and co-stimulatory molecules CD80 expression on peripheral blood B-cells and the extent of their contribution to celiac disease.
MATERIALS AND METHODS: A total of 60 male children, whose ages ranged between 8 and 14 years, participated in this study. Thirty-five were identified as having celiac disease, while the control group comprised 25 children with anti-tissue transglutaminase (TG) (immunoglobulin G [IgG]), anti-tissue TG (IgA), and deamidated gliadin peptide (DGP) IgG levels normal. The frequency CD24, CD27, and CD80 expression were measured by flow cytometry.
RESULTS: Celiac disease patients showed a substantial decrease in the percentage of CD24, CD27, and CD80 expression on B-cells compared to control groups.
CONCLUSION: These findings suggest that numerical deficiency of CD24, CD27, and CD80 expression on B-cells in the peripheral blood mononuclear cell population, that may involve the loss of auto-tolerance that plays an important role in the immune response associated with inflammation and tissue damage in celiac disease. These immunological markers may be used as diagnostic indicators for this disease.

Abstract:
BACKGROUND: One of the complications of blood transfusion is the development of red cell alloimmunization. Little published literature on the prevalence and actual significance of red cell alloantibodies among nonregularly transfused patients and the general population.
OBJECTIVES: This study aimed to estimate red cell alloantibodies’ prevalence, specificity, and clinical significance in obstetric and medical practice in Iraq.
MATERIALS AND METHODS: A cross-sectional hospital-based study involving internal medicine patients and ladies in obstetric wards of Baghdad Teaching Hospital in Baghdad/Iraq, from January 2022 to May 2022. Demographic data were collected along with detailed medical, obstetric, and transfusion history. Alloantibody screening was performed, and samples with positive results were subjected to antibody titration and identification.
RESULTS: A total of 200 patients were enrolled. Indirect antiglobulin test was positive in 15% of patients in internal medicine wards and 23% of ladies in obstetric wards, with most of the identified alloantibodies being clinically significant, against Kidd and Duffy antigen groups. Blood transfusion of more than four units to patients at internal medical wards showed a significant association as a risk for developing red cell alloantibodies (P = 0.025). For ladies in obstetric wards, there was a significant association between pregnancy loss at the time of screening and alloimmunization (P = 0.0164).
CONCLUSION: High prevalence of red cell alloantibodies in comparison to what is published worldwide. Transfusion of more than four units of blood and pregnancy loss at the time of screening were statistically significant risks for alloimmunization of the medical and obstetric populations, respectively.

Abstract:
BACKGROUND: Beta‑thalassemia (BT) is the most common hereditary hemolytic disease in Iraq. The high prevalence rate of this disorder, coupled with, frequently encountered severe clinical course, as well as the life‑long burden of comorbidities and complications, have all contributed to its status as one of the most clinically and epidemiologically significant global health issues. This has prompted our efforts to study the molecular map of BT in Baghdad city.
OBJECTIVES: The aims of this study as to identify the molecular map of BT in patients from Baghdad city with investigating the data from several clinical and disease‑associated morbidity parameters to establish potential correlation points.
PATIENTS, MATERIALS AND METHODS: The molecular profile of HBB gene of 80 transfusion‑dependent (TD) and non‑TD BT patients from Baghdad thalassemia centers was examined using multiplex polymerase chain reaction and reverse hybridization technique and direct gene sequencing.
RESULTS: In the current study, 27 different genotypes were characterized. The most predominant displayed genotypes were IVS 1.110 (G>A)/IVS 1.110 (G>A), and IVS 2.1 (G>A)/IVS 2.1 (G>A). Our data also revealed that 70% of the exhibited genotypes were homozygous, and most of those (78.6%) were TD. As for disease comorbidities, cholelithiasis (53.8%), osteoporosis (51.3%), and facial bone deformity (45%) were among the most frequently encountered in our study.
CONCLUSIONS: The compiling clinical and molecular data revealed in the current study, has indicated an aggregation of certain homozygous BT genotypes in Baghdad city that possibly influenced the comorbidity profiles of our patients.

Abstract:
BACKGROUND: Diagnosis of myeloproliferative neoplasms including polycythemia vera (PV) has been greatly improved following the identification of driver mutations at exon 12 and exon 14 of the Janus Kinase 2 (JAK2) gene. There are limited academic studies that report the frequency of the JAK2 exon 12 gene with limited number of patients.
OBJECTIVES: The aim of this study was to evaluate the frequency of JAK2 exon 12 mutations among JAK2V617F‑negative PV‑suspected Iraqi patients.
PATIENTS, MATERIALS AND METHODS: This is a retrospective study conducted at the National Center of Hematology/Mustansiriyah University from December 2019 to January 2022; patients with suspicion of PV were enrolled in this study. Screening for JAK2 exon 14 (JAK2V617F) mutations was done for all 323 patients. Out of them, there were 102 patients with JAK2V617F‑negative who retrospectively screened for JAK2 exon 12 mutations by direct sequencing (Sanger sequencing).
RESULTS: Initial evaluation for the total 323 patients suspected with PV revealed that 84 cases were mutated for the JAK2V617F gene, and 239 were unmutated. The frequency of JAK2 exon 12 was about 1% among JAK2V17F‑negative patients. The median age for all patients was 35 years. Among the total cases, 21 cases (20.59%) showed splenomegaly at the time of clinical onset sequencing of these cases revealed only one case mutated with JAK2 exon 12 (E543‑D544del).
CONCLUSION: The current study showed that the frequency of JAK2 exon 12 mutations in JAK2V617F‑negative cases was very low. Despite PV patients with JAK2 exon 12 mutations represent a small proportion of total PV cases, JAK2 exon 12 mutations should be routinely screened in JAK2V617F‑negative cases.

Abstract:
BACKGROUND: Low‑molecular‑weight heparin (LMWH) is a proven treatment for patients with venous thromboembolism (VTE) with a lower risk of VTE recurrence and lower rates of major hemorrhage compared to unfractionated heparin (UFH) and have largely replaced its use in many indications, but its use around thrombolysis remains controversial.
AIM: This study aims to evaluate the currently available evidence on LMWH use in postthrombolysis as compared to UFH.
MATERIALS AND METHODS: Embase and MEDLINE were searched between 1992 and 2022, in addition to other sources. We included experimental and observational studies that assessed the use of LMWH as compared to UFH in patients with massive and submissive pulmonary embolism (PE) in the acute postthrombolysis phase. Data were pooled to estimate odds ratios (ORs), with 95% confidence intervals for VTE recurrence, bleeding complications and 30‑day mortality.
RESULTS: Three studies were included in this systematic review: one randomized controlled trial, one prospective, and one retrospective study. A total of 299 patients were treated with UFH, and 227 patients were treated with LMWH. Patients treated with LMWH had a statistically significant lower risk of major bleeding with OR 0.41 (0.17, 0.97) P = 0.04 and 30‑day mortality with OR 0.44 (0.23, 0.85) P = 0.01. On the other hand, though the risk of VTE recurrence and clinically relevant non-major bleeding (CRNMB) were lower, this was not statistically significant with OR of 0.18 (0.03, 1.07) P = 0.06 for VTE recurrence, and OR of 0.75 (0.39, 1.42) P = 0.38 for CRNMB.
CONCLUSION: In patients with massive and submissive PE postthrombolysis, LMWH is a reasonable option for anticoagulation with lower risk of VTE recurrence, bleeding complications and 30‑day mortality when compared to UFH. However, this conclusion is largely influenced by observational data and the very limited evidence available. Certainly, more studies are needed to evaluate this clinical question.

Abstract:
BACKGROUND: Unconjugated hyperbilirubinemia is a rather common disease that affects 60% of term and 80% of preterm infants within their 1st week of life. Phototherapy is considered the safest method for the treatment of unconjugated hyperbilirubinemia in neonates, which is the most common problem in the neonatal period.
OBJECTIVES: To identify the effect of phototherapy on platelet numbers and volumes, and if the duration of treatment, gestational age, birth weight and other factors have some influences on this effect.
PATIENTS, MATERIALS AND METHODS: A prospective cohort study was conducted from November 1, 2023, to April 1, 2024. Seventy‑four neonates were enrolled in this study including males and females (1.39:1), with different gestational ages and birth weights. Neonates were selected according to the specific inclusion and exclusion criteria. Thorough history and physical examination performed with several laboratory investigations sent. Total serum bilirubin measured before starting phototherapy, after 24 hours, 48 h, 72 hours, and 4 days later. SPSS program was used to code, enter, and process the gathered data.
RESULTS: Platelet number in general decreased with increasing duration of phototherapy regardless of other parameters (P = 0.045). In correlation to the duration of phototherapy and time of jaundice appearance, it was statistically significant for only neonates who required phototherapy for more than 4 days and time of jaundice appearance between 1 and 3 days (P = 0.042). Platelets number decreased with increasing duration of phototherapy especially in low birth weight and very low birth weight neonates, P value 0.028 and 0.047 respectively. There were statistically significant values (P = 0.002 and P = 0.001) in the correlation of decreasing platelet numbers to gestational age and duration of phototherapy, especially more evident with gestational age below 37 weeks (preterm) and in periods after 24 h and 72 h. There were no statistically significant values in platelet volumes in correlation to any of the previous parameters.
CONCLUSIONS: Platelets number decreased with phototherapy management, and it is more evident with longer phototherapy duration, low birth weight and early onset, while platelet volume not affected. Hence, it is recommended to avoid unnecessary prolongation of phototherapy.

Abstract:
BACKGROUND: C‑FLICE‑like inhibitory protein (c‑FLIP) is a protein that does not merely block apoptosis signaling but also adjusts further pathways of cell death. Acute myeloid leukemia (AML), a nonhomogeneous hematologic malignancy, is the highly common form of AML among adults and is described through the clonal enlargement of myeloid blasts in the bone marrow (BM), peripheral blood, and/or else tissues.
OBJECTIVES: The aims of this study were to investigate the role of c‑FLIP and microRNA (miRNA) 708‑5p as a prospective prognostic biomarker as well as the therapeutic goal in AML.
PATIENTS MATERIALS AND METHODS: This study includes two groups of patients (40) individuals newly diagnosed AML patients, (20) AML taking chemotherapy, and (50) apparently healthy volunteers. The study was conducted at the National Center of Hematology/Mustansiriyah University. The methods employed in the analysis include total RNA extraction, complementary cDNA synthesis, and quantitative real‑time polymerase chain reaction (PCR) were used to evaluate the gene expression of cFLIP and miRNA‑708‑5p. Complete blood count to estimate some hematological parameters.
RESULTS: The expression of c‑FLIP was notably higher in both newly diagnosed and patients under chemotherapy compared to controls with fold expression (3.291 and 2.92), respectively, with a highly significant (P = 0.0001). The increase in miRNA 708‑5p expression in newly diagnosed patients with fold expression (5.345), whereas downregulation in patients under chemotherapy with fold expression (0.789) indicates that treatment may restore its levels, contributing to the suppression of c‑FLIP and promoting apoptosis.
CONCLUSION: The c‑FLIP and miRNA708‑5p gene might be used as a biological marker for the AML initial diagnosis. The researches emphasize the role of miRNA 708‑5p as a tumor suppressor, which negatively regulates the antiapoptotic protein c‑FLIP, indicating its potential as a therapeutic target in AML treatment. By modulating the levels of miRNA708‑5p, it may be possible to regulate the expression of c‑FLIP, thus enhancing the effectiveness of apoptosis‑inducing therapies. This suggests the promising development of miRNA‑based therapies as part of AML treatment strategies. Furthermore, miRNA 708‑5p can act as a prognostic indicator in AML, with its expression levels offering valuable insights into disease progression and patient response to treatment. Further research into miRNA 708‑5p can lead to a better understanding of its role in AML pathogenesis and its potential applications in clinical practice.

Abstract:
BACKGROUND: The classification of acute myeloid leukemia (AML) has evolved extensively over the last 20 years significantly, impacting the diagnosis and prognosis of the patients. The lysine (K)-specific methyltransferase 2A (KMT2A) gene, which has more than 80 gene fusions, is present in approximately 10% of all leukemias. Most KMT2A rearrangements are associated with adverse prognosis and need heavy chemotherapy protocol upfront.
OBJECTIVE: This study aims to study the prevalence of KMT2A gene fusion among Iraqi patients with AML and its association with clinical and hematological parameters and patients’ outcomes.
PATIENTS, MATERIALS, AND METHODS: A prospective cohort study conducted between December 2020 and May 2022 enrolled 115 Iraqi adults newly diagnosed with AML at the Hematology Unit of Baghdad Teaching Hospital. The patients were also monitored at this facility during the study period. Genetic rearrangements were detected using the Leukemia Q‑Fusion Screening Kit through Real-Time Quantitative Reverse Transcription PCR (RT‑qPCR) analysis.
RESULTS: KMT2A rearrangements were identified in 23 (20%) patients. The most common was t(10;11) which presented in 15 (13%) patients, followed by t(9;11) in 5 (4.3%) patients and t(11;17) in 3 (2.6%) patients. Patients with KMT2A rearrangements were significantly older and more likely to have splenomegaly. At 1‑month posttreatment, they had significantly lower red blood cell counts and hemoglobin levels and higher blast percentages. Only 4.3% achieved complete remission (CR) compared to 76.1% without KMT2A rearrangements, with a significantly higher mortality rate (30.4% vs. 5.4%, P = 0.0001). Regarding the treatment response, no significant differences were observed among the different fusion types of KMT2A rearrangements.
CONCLUSION: KMT2A rearrangements are more prevalent among Iraqi AML patients compared to the global trend and are associated with older age, higher rates of splenomegaly, poorer hematological recovery, and worse outcomes, regardless of the KMT2A rearrangement fusion type.

Abstract:
BACKGROUND: Acute lymphoblastic leukemia (ALL) is an abnormal clonal proliferation of early hemopoietic precursor cells in bone marrow (BM). There are certain cytokines like tumor necrosis factor alpha ( TNF-α) which plays a crucial role in the development and progression of malignant process, and other enzymes like lactate dehydrogenase (LDH) which has prognostic value.
OBJECTIVE: The aims of this study were to evaluate the level of serum TNF-α and LDH in ALL patients at diagnosis and post-induction chemotherapy.
PATIENTS, MATERIALS, AND METHODS: This was an observational–analytical study, which was done in Ibn-Sina Teaching Hospital in the period between May 2023 and November 2023. It included 22 newly diagnosed patients with ALL. All patients underwent complete blood count, bone marrow examination, flowcytometry, serum TNF-α and LDH at diagnosis and post induction chemotherapy.
RESULTS: In 22 patients with ALL, at diagnosis, the means of serum TNF-α (97.89 ± 52.945 ng/l), serum lactate dehydrogenase(1138.94 ± 430.10 IU/l), and percentage of blasts cells in BM (0.742 ± 0.181) in B-ALL. The means of serum TNF-α (165.33 ± 23.437 ng/l), serum lactate dehydrogenase (1633.33 ± 497.426 iu/l), and percentage of blasts cells in BM (0.816 ± 0.125) in T-ALL were statistically higher than those among the controls (s.TNF-a (18.09 ± 6.795 ng/l), s.LDH (142.59 ± 61.626 IU/l), and percentage of blasts cells in BM 0.0 ± 0.0) with P = 0.000 for all parameters mentioned, respectively. After induction phase chemotherapy in B-cell ALL , there were a significant reduction noted for serum TNF-α (29.26 ± 18.648 ng/l) and LDH levels (245.47 ± 154.592 IU/l) and a significant decrease in the percentage of blasts cells (0.07 ± 0.060).also in T-cell ALL there were a significant reduction noted for serum TNF-a (26.00 ± 11.135 ng/l) serum LDH (347.66 ± 160.300 IU/l) and percentage of blasts cells in bone marrow (0.06 ± 0.046). All of the postchemotherapy acute leukemia cases with lower TNF-α levels had complete remission (100%).
CONCLUSIONS: There were significant increases in serum TNF-α and LDH in ALL patients at diagnosis; while after induction, there was a significant reduction in their levels. Complete remission from the disease was associated with lower levels of serum TNF-α in newly diagnosed patients.

Abstract:
BACKGROUND: Currently, about 50% of diffuse large B‑cell lymphoma patients are relapsed following their complete response to first‑line therapy. The treatment strategy for fit patients with relapsed refractory diffuse large B-cell lymphoma (R/R DLBCL) has been done with salvage therapy with non-cross resistant combination chemo-immunotherapy regimens followed by high‑dose chemotherapy and autologous stem cell transplantation (ASCT).
OBJECTIVES: The aim of study was to evaluate the outcome of ASCT for R/R DLBCL in relation to certain prognostic parameters.
PATIENTS, MATERIALS AND METHODS: This is retrospective study, conducted from May 2014 to December 2022, at Hematology and BMT Center of Medical City Complex in Baghdad. Thirty‑six patients with R/R DLBCL were investigated pre‑ and post‑ASCT; the recorded data included patient disease status pre-transplant, early mortality rate, and type of response at day 100 post-transplant and, survival rate, relapsed rate, and mortality at the end of the study were documented accordingly.
RESULTS: The mean age of DLBCL patients in this study was 41.3 (14–65) years, post‑ASCT at day 100; there were 33 (91.6%), 2 (5.5%), and 1 (2.7%) patients in complete remission, relapsed progressive disease, and death, respectively, At 3‑year posttransplant, the overall survival (OS) was 71%, whereas the event‑free survival (EFS) was 59%. According to disease status pre‑ASCT, the OS was 62%, 80%, and 66% with P = 0.7, whereas the EFS was 66%, 60%, and 50% with P = 0.5 for CR, UCR, and PR, respectively.
CONCLUSION: Iraqi bone marrow transplant center data showed acceptable OS and EFS results in the treatment of R/R DLBCL patients in areas where there is no more option in terms of better OS and EFS but with insignificant relation to the available prognostic factor.

Abstract:
BACKGROUND: Gene expression profiling has become a fundamental tool in cancer diagnosis and management. B-cell non-Hodgkin lymphoma (B-NHL) is a group of malignant neoplasms originating from the lymphoid tissues, mainly the lymph nodes and the gene expression technique was used to unravel its complexity and aid in clinical decision-making.
OBJECTIVES: The aims of this study were to find the significance of gene expression profiling focusing on colony-stimulating factor 1 receptor (CSF1R), myeloid differentiation factor 88 (MyD88), and tumor necrosis factor-α (TNF-α) as a promising approach in B-NHL diagnosis and their comparison with healthy controls.
PATIENTS, MATERIALS AND METHODS: The current clinical prospective study was mediated from June 1, 2021, to December 30, 2022, of NHL patients in Kurdistan, Iraq. Seventy-three patients were recruited from Nanakali Hospital for Blood Diseases and Cancer, Erbil. The integration of gene expression biomarkers uses quantitative real-time polymerase chain reaction technique to diagnose B-NHL. Specifically, we focused on three key genes MyD88, TNF, and CSF1R whose expression profiles were analyzed in B-NHL patients and controls. We leveraged a dataset to explore gene expression patterns in B-NHL and applied classification algorithms to distinguish between B-NHL patients and controls.
RESULTS: The initial results show the overall lower CSF1R expression in B-NHL as compared to the controls and a significant reduction in CSF1R expression in females (≤50 years and >50 years). The result considers lower CSF1R expression in B-NHL males (≤50 years) and higher but not significant in males (>50 years).
CONCLUSIONS: These B-NHL-expressed genes may be considered potential diagnostic markers with their meaningful comparisons to control groups, and they could be proposed to guide the management of patients and facilitate their stratification into clinical trials.

Abstract:
BACKGROUND: β-thalassemias are widely distributed in Mediterranean and Middle Eastern countries, including Iraq. There are more than 400 transfusion-dependent β-thalassemia patients registered in the thalassemia center. β-thalassemia is a significant problem in Karbala as well as other regions of Iraq. The detection of the most frequent mutations is significant to the implementation of an effective preventive program in this area because of the significant burden it places on the local health authorities, patients, and their families.
OBJECTIVES: To define the most common mutations and their frequencies among patients with transfusion-dependent β-thalassemia and to evaluate the reverse hybridization strip assay method for the detection of β-thalassemia mutations.
PATIENTS, MATERIALS AND METHODS: Sixty transfusion-dependent β-thalassemia patients were recruited from the thalassemia center in Karbala. Blood samples were aspirated from each patient just before blood transfusions for CBC, reticulocyte count, DNA extraction, PCR amplification, and identification of the mutations by reverse hybridization technique using the β-Globin strip assay method.
RESULTS: A total of 60 patients with 120 chromosomes were studied, searching for the most common mutations causing β-thalassemia. Among the twelve identified mutations, the six most frequent mutations represented 79.16% of all β-globin defects. These mutations were IVSII-1 (30.83%), IVSI-110 (15.83%), Codon 5 (10.83%), Codon 44 (8.33%), IVSI-1 (6.67%), and IVSI-5 (6.67%). The detection rate of the method used in our population was 96.66%.
CONCLUSION: The most frequent mutations encountered were IVSII.1 and IVSI-110, while IVS 2.745 was the least common mutant allele. Reverse hybridization strip assay molecular techniques used in the current study provide an extremely quick, precise, and simple to carry out molecular diagnostic technique for the detection of β-thalassemia mutations.

Abstract:
BACKGROUND: Chronic lymphocytic leukemia (CLL) is a disease characterized by an uncontrolled proliferation of malfunctioning mature B‑lymphocytes. It represents a variable range of clinical presentation and prognoses. Understanding the demographic and cellular characteristics of CLL patients can aid in better disease management and treatment outcomes.
OBJECTIVES: To identifying hematological parameters and patterns and potential markers that could assist in better diagnosis and of CLL in the local population.
PATIENTS, MATERIALS AND METHODS: A retrospective analysis of 124 cases of newly diagnosed CLL was conducted. Data were collected from reports over 2 years (April 2022-April2024), including demographics, Hb levels, WBC counts, platelet counts and expression of CD markers (5, 19, 20, 23, 200, FMC7, LAIR1 and others) using flow cytometry on peripheral blood specimens. Based on FC findings, patients were categorized into two groups for better assessment; definite diagnosis CLL and possible diagnosis CLL; then further subdivided into poor prognosis CLL and good prognosis CLL.
RESULTS: Male patients represented 59.5% of cases and females were 40.5% with a median age of 61 years at diagnosis. The mean Hb level was 109 ± 2 g/L, the mean WBC count was 58.0 ± 25.0 × 109/L, and the mean platelet count was 190 ± 40 × 109/L. CD5 was positive in 97.6% of cases, with CD23 in 96%.
CONCLUSION: This study provides an overview of the demographic and cellular marker characteristics of CLL patients in FC unit. The findings underscore the heterogeneity of CLL immunophenotype and the importance of detailed characterization in improving patient management protocols; however, further research is warranted to correlate these findings with other parameters of disease burden and prognosis to optimize the therapeutic approaches for CLL patients.