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Introduction: Leukocytes causing a wide variety of side effects after transfusion are present in all blood products prepared by standard methods. As a consequence, the use of filter technology for leukoreduction has been widely practiced .According to AABB accreditation in 1996, leukoreduced blood components must contain less than 5×106 leukocytes per unit, but sometimes this value is higher even in leukoreduced products. In this study we did absolute leukocyte count in filtered (home made bedside filter) packed cell units by two methods of true count as standard method and CD45 MoAb.

Materials & Methods: 93 packed cell units were stored at 4°c and filtered by two types of home-made filters according to manufacturer's instructions. Furthermore, eight packed cell units were filtered by Europe certified control group filters (bio-fil). Sample preparation was done according to True count kit and CD45 MoAb procedures and analysis was performed by flowcytometry (EPICS-XL,coulter) and (Partec PAS III).The results were then analyzed by chi2 test via SPSS.

Results: The mean values of leukocyte count/unit by anti CD45 and True count method were 9×106 and 10×106 respectively in 55 pre-revised filter bags these figures were 4.2×106 and 4.8×106 in 30 post-revised filters, whereas the mean leukocyte count/bag in eight control filters was 2.3×106,we selected randomly eight test units out of 53 and 30 pre-revised and post-revised filtered bags, respectively(equal with number of units in the control group) to compare the test and control groups The mean values of leukocyte count/bag in pre-revised test group was 7.9±5.4×106 and in postrevised test group was 4.2 ×106 but in the control group it was 2.3 ×106 (p value<0.05).

Discussion: According to the results, the mean leukocyte count/bag in pre-revised group was higher than AABB standard. 38.2 % of bags had lower and 61.8 % had higher leukocyte count than the standard value (48.9 to 74.6 % with CI=95 %), this indicates the necessity of revision in product technology of homemade filters. relevant manufacturer revised the product technology and material accordingly, so that new filters (post-revised group) reduced leukocytes within standard limits (leukocyte count in 6 bags were out of standard range).In post-revise filter group, 20 % had a leukocyte count of more than 5×106 while 80% showed less than this value (5.7%-34.3% with CI=95%).There is a significant difference between control and pre-revised test groups (p=0.03).In post-revised test group, despite significant differences, the mean values of leukocyte count/bag were within normal standard range. The results of this research caused home-made filter production with higher quality.

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Background: Hepatitis C virus (HCV) infection is the most common transfusion transmitted disease in poly-transfused patients worldwide. In this study we aimed to evaluate the effects of pegylated interferon alfa-2a (PEG-IFN A-2a) in reducing serum ALT and eradicating serum hepatitis C virus (HCV) RNA in HCV infected polytransfused thalassemic patients.

Materials and Methods: A cohort of 51 HCV-RNA positive thalassemic patients were enrolled to our study and received 180 µg PEG-IFN A-2a once-weekly for 48 weeks. The primary end point was sustained virological response (SVR). The secondary outcome was normalization of ALT. Patient safety was assured by monthly, and if needed, weekly laboratory assessment and visits.

Results: Of 52 patients, 42 participants completed the treatment schedule. A sustained virological response (SVR) was attained in 22/51 (43%) cases. Among non-responders or relapsers to previous HCV antiviral therapy, 9/27 (33%) attained an SVR. Five patients died during treatment and 3 subjects discontinued the therapy because of adverse effects. Adverse events were generally mild, and laboratory abnormalities were rare.

Conclusion: A course of 48-week PEG-IFN A-2a monotherapy is effective in eradicating HCV-RNA during treatment. But about one third of thalassemic patients would relapse within 6 months of treatment schedule completion, in whom combination therapy is needed.

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Background: Thalassemia is a series of hemoglobinopathies in which the production of perfect hemoglobin is completely or partially suppressed. Using injectable iron chelators have been dominating treatment for the iron overload caused by recurrent blood transfusions in thalassemic patients, however, a new oral iron chelating drug (Exjade) have been recently introduced and might be cost effective compared to previous treatment methods. This study was undertaken to evaluate the cost of Exjade in comparison with injectable iron chelators. Patients and Methods: In this retrospective study, we calculated the cost of iron chelation with Deferoxamine mesylate or Desferal in three groups of patients including those with optimum moderate and poor compliance. Afterwards, we compared the cost with the cost of iron chelation using Exjade. The cost of drugs and treatment for complications caused by iron overload were both taken into account. Results: The average cost of treatment per year with Deferoxamine mesylate was 85601032 Rials for patients with poor compliance, 62739714 Rials for patients with moderate compliance, and 50118376 Rials for patients with optimum compliance. In addition, according to the latest price of Exjade in Iranian market, we found out a regular oral iron chelation therapy using Exjade, with a dose of 20 mg/kg, to cost 76650000 Rials per year. Conclusion: Our findings indicate that using Exjade is cost-effective for those patients who have poor compliance to parenteral treatment. More investigations should be implemented to find the social and economic impact of Exjade therapy on quality of life among patients needing iron chelation therapy. Keywords: Thalassemia, hemoglobinopathies, iron chelating agents, deferasirox, deferoxamine

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Background: Hemoglobin S arises is the result of a point mutation (A-T) in the sixth codon on the -globin gene on chromosome 11 causing sickle cell anemia. The presence of fetal hemoglobin in infancy plays a relatively protective role for vaso-occlusive symptoms that are the major contributor for the morbidity and mortality among patients with sickle cell anemia. hydroxyurea, an s-phase-specific and non-DNA-hypomethylating chemotherapeutic agent is capable of inducing HbF synthesis. Materials and Methods: We reviewed the records of 28 sickle cell anemia patients, aged 4-52 years, treated with hydroxyurea to study the drug’s side effects. Results: In our study, the most common adverse effect was dermatologic complication which occurred in 15 patients (53.5%). The gastrointestinal side effects were nausea, vomiting, abdominal pain and anorexia occurring in 3 patients 10.7%. The neurologic adverse effects were uncommon and occurred in 4 patients (14.3%). Conclusion: Side effects of hydroxyurea were common but mild to moderate, benign and transient. Starting a low dose of hydroxyurea (10 mg/kg per day) and increasing the dose slowly in pediatric and adult patients with sickle cell anemia can be tolerated well, without serious side effects. Keywords: Side effect, hydroxyurea, sickle cell, anemia.

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Background: Human leukocyte antigens (HLA) are polymorphic cell surface proteins. Distribution of HLA alleles vary among different racial and ethnic populations in unrelated stem cell registries. Determination of HLA allele frequencies in different ethnic groups is useful for population genetic analyses. Materials and Methods: Based on data available from the Iranian Stem Cell Donor Registry, HLA-A, B, DRB1 allele frequencies were evaluated from 244 individuals who were recruited as unrelated volunteer donors by PCR-SSP method in people of Fars ethnicity living in Tehran, Iran. Results: The most frequent alleles found were HLA-A*02(19.8%), HLA-A*03(13%), HLA-A*11 and -24 (12.5%), HLA-B*35(17.7%) HLA-B*51(13.2%), HLA-DRB1*11(20.8%), whereas HLA-A*34 and HLA-A*44 (0.2%), HLA-B*47, B*54, B*56, B*73(0.2%), and HLA-DRB1*09 (0.4%) were the least frequent alleles. Conclusion: Identifying HLA allele frequencies in different ethnic groups, helps in designing a better plan for development of donor centers in different provinces of a country, and a more precise prediction of donor size in the registry, in addition to finding suitable donors for patients in need of hematopoietic stem cell transplantation. Keywords: HLA, unrelated donors, ethnic groups, Iran

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Background: Transfusion is the mainstay treatment of patients with thalassemia major and occasionally in thalassemia intermediate. Alloimmunization is an unwanted side effect of blood transfusion. The present study intended to determine the frequency of alloimmunization in patients with β- thalassemia major and thalassemia intermediate in Southwest Iran. Patients and Methods: This was a cross-sectional study on 133 transfusion dependent β-thalassemia patients at Shafa hospital-in Southwest Iran. The method of antibody screening was the tube method. All panel test phases were done at immunohematology laboratory of Iranian Blood Transfusion Organization. Results: There were 66 males (49.1%) and 67 females (50.9%) with the mean age of 17.5 years (SD±7.5) included in this study. The antibody screening panel test was positive in 42 patients (32.06%). Twenty five patients (18.7%) had alloantibody and 17 patients (12.7%) also had autoantibody. The predominant pattern of alloimmunization was alloantibodies against RH sub groups system in 55 percent of patients and 33% of patients had alloantibodies against Kell system. Three important factors that significantly influenced the frequency of alloimmunization were: age at the first blood transfusion, splenectomy and β- thalassemia intermediate. Conclusion: Alloimmunization is a common complication among patients with transfusion dependent β-thalassemia in Khuzestan province, Iran. Matching the selected donors with recipients based on the extended red blood cell antigen typing may decrease the incidence of alloimmunization. Key Words: Alloimmunization, thalassemia major, thalassemia intermediate, RH blood group, Kell blood group.

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Background: Hemophilia B is an X-linked hereditary disorder of blood coagulation system which is caused by factor IX (FIX) deficiency. Factor IX is a plasma glycoprotein that participates in the coagulation process leading to the generation of fibrin. Replacement of factor IX with plasma-derived or recombinant factor IX is the conventional treatment for hemophilia B to raise the factor IX level to therapeutic range. Recently, gene therapy has been regarded as a promising approach to treat hemophilia B. This study was aimed to express the factor IX in human amniotic membrane-derived mesenchymal stem cells (hAM-MSCs). Materials and Methods: Human amniotic membrane-derived mesenchymal stem cells were isolated and characterized from amnion membrane. Factor IX from commercially available plasmid was sub-cloned into pcDNA3.1 vector. Recombinant pcDNA3.1-FIX construct was confirmed by PCR, enzymatic digestion and DNA sequencing. Mesenchymal stem cells were transfected with the recombinant vector. Expression of factor IX was determined by RT-PCR, ELISA and its biological activity assay was performed using aPTT. Results: Isolated hAM-MSCs expressed specific mesenchymal stem cells markers and were able to differentiate to osteocytes and adipocytes lineages. hAM-MSCs expressed hrFIX at mRNA and protein level. The maximum amount of hrFIX was 120 ng/ml at 72 hrs after hAM-MSCs transfection. This hrFIX was biologically active (11% activity), formed fibrin clot in aPTT test and caused more than two fold decrease in clotting time. Conclusion: The hAM-MSCs expressing factor IX would be useful for gene therapy of hemophilia B. However further studies are required to prove these finding. Key words: Hemophilia B, amnion membrane, mesenchymal stem cell, factor IX, gene therapy.

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Background: In acute myeloblastic leukemia, a large number of tumor suppressor genes are silenced through DNA methylation such as CDKN2B & p73. Wnt inhibitory factor 1 (WIF1) and Dickkopf-3 (DKK-1) are negative regulators of Wnt signaling pathway. In the present study, we evaluated the methylation status of WIF1 and DKK-1 genes in acute myeloblastic leukemia patients. Patients and Methods: Blood samples were taken from 120 AML patients and 25 healthy control subjects. DNA was isolated, treated with sodium bisulphite, and examined using methylation-specific polymerase chain reaction (MSP) with primers specific for methylated and unmethylated sequences of the WIF1 and DKK-1 genes. Results: The frequency of aberrant hypermethylation of WIF1 and DKK-1 genes in acute myeloblastic leukemia patients were determined to be 35% (42/120) and 28.3% (34/120), respectively. In addition, for all subjects in control group, methylation of WIF1 and DKK-1 genes were negative. Patients with M0 subtype of FAB-AML had the highest incidence of hypermethylation of WIF1 (P = 0.003) and DKK-1 (P = 0.005) genes. Conclusion: The present study showed that, like many solid tumors, WIF1 and DKK-1 genes methylation also occurs in acute myeloblastic leukemia. The study of other antagonists of Wnt signaling pathways are recommended. Key words: AML, Wnt inhibitory factor 1, dickkopf, DNA methylation.

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Background: Beta thalassemia gene mutations are among common mutations in southwest Iran. However, Hemoglobin E (Hb E) and Hb E/β⁰ thalassemia account for a small number of hemoglobinopathies in Iran. This is the first study to directly address the existence of Hb E and consequently Hb E/β⁰ thalassemia in southwest Iran. Methods: This retrospective study discovered seven cases of Hb E/β⁰ thalassemia among 700 patients with hemoglobinopathies referring to Health Institute and Research Center for Thalassemia and Hemoglobinopathy in southwest Iran. EDTA and clot blood samples were obtained and analyzed for complete blood counts, hemoglobin electrophoresis, LDH, bilirubin, ferritin and amplification refractory mutation system (ARMS) technique by polymerase chain reaction (PCR) and DNA sequencing. Results: Out of 700 cases, seven patients with Hb E/β⁰ thalassemia were detected (1%). Four patients were classified into non-transfused dependent Hb E/β⁰ thalassemia and three cases were classified into transfusion dependent Hb E/β⁰ thalassemia group. Alpha thalassemia (deletional and non-deletional) and XmnI gene polymorphism were not found in either of cases. Conclusion: Hb E/β Thalassemia is not a common hemoglobin disorder in southwest Iran. Phenotype heterogeneity is common in Iranian patients from a mild asymptomatic anemia to severe anemia that can be presented in the early years of life. This was the first report of Hb E/β⁰ thalassemia from Iran. Keywords: Hb E/β⁰ Thalassemia, Southwest Iran, Transfusion dependent, Non-transfusion dependent, Hb E mutation.

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Background: Chronic myeloid leukemia is a clonal myeloproliferative disease which is characterized by bcr/abl translocation. With the emergence of tyrosine kinase inhibitors such as imatinib mesylate, significant improvement has been made in treatment of this disease. However, drug resistance against this medicine is still an obstacle. SIRT1 is a gene with deacetylase activity which has been detected to have increased expression in many cancers. We aimed to determine if SIRT1expression could play a role in the emergence of drug resistance in patients with chronic myeloid leukemia being treated with imatinib mesylate. Methods: 48 patients with chronic myeloid leukemia referred to Dr. Shariati Hospital, Tehran, Iran, were studied. A venous blood sample of patients was collected, RNA was extracted and then cDNA were synthesized. SIRT1 gene expression was done by real-time PCR. The ratio of SIRT1 expression to ABL control gene was calculated. After calculation of CT for target gene and control gene, &DeltaCT was calculated. The results of SIRT1 expression levels in patients with chronic phase of CML were compared with that of the control group. Results: 48 patients with chronic myeloid leukemia aged 15-64 years (mean: 40 years) were enrolled. 59% of the participants were men. The highest and lowest mean BCR-ABL expressions in drug-resistant patients were 1% and 57%, respectively. The results of analyzing the value of &DeltaCT for SIRT1 gene revealed that patients who were drug-resistant to imatinib mesylate had a lower value of &DeltaCT for SIRT1 than those who were not drug-resistant (P<0.05). Conclusion: SIRT1 gene expression in patients resistant to imatinib mesylate was significantly higher than patients who were not drug-resistant.

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Autoimmune lymphoproliferative Syndrome (ALPS) is a rare inherited disorder of apoptosis. It usually presents with chronic lymphadenopathy, splenomegaly, and symptomatic cytopenia in a child. Herein, we report a 14-year-old boy with symptoms misdiagnosed as hemophagocytic lymphohistiocytosis who was treated before ALPS was diagnosed for the patient. This case should alert pediatricians to consider ALPS in differential diagnosis of a child with lymphadenopathy, splenomegaly, and cytopenia.

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Background: Considering the increasing number of patients with hemophilia and infrastructure requirements for a comprehensive approach, development of a recombinant factor has become a milestone. The objective of this study was to assess the safety, efficacy and non inferiority of Safacto (Recombinant factor VIII) compared with plasma-derived factor in the treatment of hemophilia A. Methods: 10 patients with severe hemophilia A were enrolled in this study. Each patient was treated by a 40-50 IU/kg infusion of either plasma derived or recombinant factor VIII after initiation of each of 4 consecutive hemarthrosis episodes in a triple-blind prospective crossover permuted block randomizing method. Clinical efficacy scale score and in vivo recovery of factor VIII was assessed in each of the treated bleeding episodes. Any adverse event was also recorded. Results: The mean±SD level of factor VIII in the plasma versus recombinant groups was 111.5±39 and 115±39, respectively without any significant difference. Response scaling method which assessed pain and range of motion revealed equalized scores along with in vivo recovery, hence treatment success rate was comparable in both groups. One non-recurring, mild skin rash reaction occurred simultaneous with the administration of plasma derived factor. Conclusion: Safacto (r-FVIII) is safe and effective and non-inferior to plasma derived factor VIII in the treatment of hemophilia A related bleeding events.

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Background: Several studies have examined the presence of DNA methylation of CpG islands in leukemia. Methylation of SOX17 and RUNX3 genes may play a role in leukemogenesis through silencing tumor suppressor genes. We investigated the methylation status of SOX17 and RUNX3 genes in patients with acute leukemia.   
Methods: In this case-control study, peripheral blood samples from 100 AML and 100 ALL patients and 100 healthy controls were collected. Isolated DNA was treated with sodium bisulfite and methylation status was examined by methylation specific PCR (MS-PCR) with primers specific for methylated and unmethylated sequences of SOX17 and RUNX3 genes.
Results: The frequency of hypermethylation of SOX17 and RUNX3 genes were 36% and 28%I in patients with acute myeloid leukemia (AML), and 21% and 22% in patients with acute lymphoblastic leukemia (ALL), respectively. Aberrant methylation of these genes was found in all FAB classifications of AML and ALL. Hypermethylation of SOX17 (P=0.055) and RUNX3 (P=0.003) genes were associated with FAB-M0 and M1 subtypes of AML, respectively. Also, aberrant methylation of RUNX3 gene was associated with FAB-L1 subtype of ALL (P=0.053). There was not any significant association between hypermethylation of SOX17 and RUNX3 genes and clinical parameters of patients with leukemia including sex, age, WBC, and platelet counts.
Conclusion: Hypermethylation of SOX17 and RUNX3 genes was seen in patients with acute leukemia. Moreover, no significant association was observed between hypermethylation of SOX17 and RUNX3 and induction of remission.

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Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most known enzyme defects in Iran with various genetic mutations. We aimed to study the predisposing factors of hemolysis in children with G6PD deficiency.
Methods: This study was done during 2007-2012 in two referral centers of Mofid Children’s Hospital and Baqiyatallah Hospital, Tehran, Iran. The hospital records of the patients were fully reviewed and questionnaires for each patient were filled for the date of admission, initial symptoms, initial laboratory results, family history and history of any drug consumption, infection or fava bean ingestion. 
Results: Medical records of 192 children with mean age of 4.2 years (1 month to 14 years) were extracted. 68.2% of the cases were male. Hemolytic crises were significantly more common in spring which is the peak time for fava bean consumption and occurred more frequently in those with a family history of G6PD deficiency especially in females. The most common initial symptoms were jaundice (71%), dark color urine (49%), fever (34.4%), and pallor (24.5%), followed by abdominal pain (16.7%). Fava bean intake (93%) was the first etiological agent triggering hemolysis followed by infectious agents and drug consumption. Initial hemoglobin level was significantly lower in male patients.
Conclusion: Regarding the high prevalence of G6PD deficiency in Iran, we should emphasize on education of parents and physicians about the disease and prevention of fava bean ingestion in people with G6PD deficiency.

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Background: The development of anti-red blood cell alloantibodies remains a major problem in transfusion of blood in thalassemia major patients. Also, Autoantibodies can result in clinical hemolysis and difficulty in cross-matching blood. We studied the frequency of red blood cell alloimmunization and autoimmunization among thalassemia patients who received regular transfusions in Ilam province of Iran. 
Methods: This study was carried out on 110 multiply transfused patients with thalassemia major. The saline method, Albumin method, direct/indirect coombs’ and Three cell panel test used for detection of red blood cell alloantibody/ autoantibody. 
Results: 12 patients out of total 110 patients (10.9 %) developed alloantibodies and 2 (1.81 %) developed autoantibodies. Rh and Kell blood group system alloantibodies were most commonly found, with the majority of patients being transfused with blood matched for ABO and D antigens only. 
Conclusion: This study suggests screening RBC antigens prior to transfusion. Our findings accentuate the necessity of antigen typing of supposed to be transfused red blood cells and screenings tests before the first transfusion, at least for Rh (Rh system) and Kell (Kell system) antigens.

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Background: As a T helper type 1 (Th1) derived cytokine, Interferon gamma (IFN-γ) is an important regulator of inflammatory immune responses. Furthermore, IFN-γ plays an essential role in defense against tumors and intracellular pathogens. This study was designed to assess the pattern of IFN-γ production in human leukemic (Jurkat and Molt-4) T cell lines in vitro.
Methods: Jurkat and Molt-4 cells were cultured in whole RPMI-1640 media. The cells were imbedded at a density of 2×106 cell/ml. The cells were stimulated with different concentrations of Phytoheamagglutinin (PHA) (2-10 µg/ml), phorbol myristate acetate (PMA) (1-25 ng/ml) or lipopolysaccharide (LPS) (1-4 μg/ml) for activation and cytokine production for 48 hours. Then the cell-conditioned media were used for IFN-γ assay. Analysis of variance (ANOVA) was done for comparing the groups statistically.
Results: PHA and PMA substantially augmented IFN-γ level in human leukemic T cells (Molt-4 and Jurkat) in a dose-dependent manner after 48 hours of incubation compared with untreated control cells, whereas LPS did not have any significant effect on IFN-γ production in human leukemic T cell lines compared with unstimulated cells.
Conclusion: human leukemic Jurkat and Molt-4 T cell lines could potentially produce IFN-γ with different amounts. PHA was a more potent stimulator of IFN-γ production than PMA. Molt-4 cell line could produce more IFN-γ than Jurkat cell line. These cells could be appropriate for studying the mechanisms of action of immunomodulators as well as screening the IFN-γ stimulators/inhibitors.

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Background: Dimethyl Sulfoxide (DMSO) is a solvent most broadly used as a cryopreservative agent. Antitumor effects of DMSO is a recently recognized phenomenon. In this study, cytotoxic effects of DMSO on human monocytes and T leukemic cell lines has been investigated in vitro.
Methods: Human leukemic T cells (Molt-4 and Jurkat) and monocytes (U937 and THP1) were cultured in complete RPMI mediums. The cells at different logarithmic growth phases were incubated with different concentrations of DMSO (0.1, 0.2, 0.5, 1, 2 and 5%). Then viability and proliferative response of leukemic cell lines was assessed by trypan blue dye exclusion (TB test) and MTT assays, respectively.
Results: DMSO has a cytotoxic effect on the leukemic cells used in this study; dose and time-dependently. This cytotoxicity for all of these leukemic cells was shown at ≥ 2% concentrations of the DMSO after 24, 48 and 72 hours’ incubation time. Moreover, there was not any significant difference between DMSO cytotoxicity in these different leukemic cell lines.
Conclusion: All of the used leukemic cells showed sensitivity to DMSO at ≥2% concentrations time dependently. This sensitivity significantly increased with time. DMSO might be a cytotoxic agent for leukemic cells. It might be a useful candidate in design of chemotherapeutic protocols for leukemia as well as other cancers. 

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Macrophage activation syndrome (MAS) is a rare feature of rheumatic disorders in children and adolescence and its presentation as the first symptom of rheumatic disorders is very infrequent.
A 9-year-old girl, in whom MAS developed, was admitted to our Hospital in Tehran, Iran. She suffered from high grade fever and rash followed by multiple joint swelling months afterwards. Bone marrow aspiration and biopsy showed normocellular marrow with a cellularity of 90%. Benign-looking macrophages were remarkably increased; many of them showed hemophagocytic features. According to the presentation of long-standing fever and observation of “hemophagocytic macrophage” in bone marrow, MAS was diagnosed for the patient. Additionally, due to recurrent joint swelling in following months, she was diagnosed to be affected by “Juvenile Idiopathic Arhtritis” complicated by MAS.
MAS is a rare complication of rheumatic disorders which should be considered as the first presentation of rheumatic disorders in children specifically in those presenting with high fever, hepatosplenomegaly, lymphadenopathy and severe cytopenia. 

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Background: β-Blockers have shown considerable cytotoxic, anti-tumor and anti-angiogenic effects. Metoprolol, a β-Blocker with anti-inflammation, anti-tumor and anti-angiogenic properties has been widely used for treatment of some cardiovascular diseases such as angina, hypertension, heart failure and myocardial infraction. Limited data exist about the cytotoxic effects of metoprolol on human cancer cells. The aim of this study was to investigate the cytotoxic effect of metoprolol on U937 and MOLT-4 cells in vitro. 
Methods: Human leukemic T cell (MOLT-4) and monocyte (U937) were cultured in Roswell Park Memorial Institute (RPMI) 1640 complete medium. Then, the cultured U937 and MOLT-4 cells were treated with different concentration of metoprolol (1, 10, 50, 100, 500 and 1000 μg/ml) for 24, 48 and 72 hours. The cytotoxicity of metoprolol was determined by using MTT (3-[4, 5 dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay. 
Results: Metoprolol significantly decreased the viability of U937 and MOLT-4 cells at 1000μg/ml (3740.14µM) concentration after 48 hours incubation time (P<0.01). In addition, metoprolol significantly reduced the viability of U937 cells at ≥500 μg/ml (≥1870.07µM) concentrations after 72 hours incubation time (P<0.001). Moreover, metoprolol significantly decreased the viability of MOLT-4 cells at ≥100 μg/ml (≥374.01µM) concentrations after 72 hours incubation (P<0.001). 
Conclusion: According to the results of this study, metoprolol showed cytotoxic effect on U937 and MOLT-4 cells dose and time dependently. Therefore, metoprolol might have potential implication in therapy of leukemia as well as other malignancies.