amir ali hamidieh

Cancer is among the serious health problems of the medical world, for treatment of which severe treatments are used. However, the prognosis of cancer patients is still poor. The application of NK cell-derived exosomes (NK-Exo) is a new method for cancer immunotherapy. These nanoparticles with a size range of 30-120 nm are a small model of mother cells. In this study, the anti-tumor activity of NK-Exo and LAK-Exo (activated NK cell-derived exosome) against acute myeloid leukemia (AML) is investigated in vitro.

The MACS method was performed for the separation of NK cells from the buffy coats of healthy donors, and an EXOCIBE kit was used for the isolation of NK-Exo. After treating the KG-1 cell line with different doses of NK-Exo, MTT assay, and annexin V-PE were done to evaluate cell proliferation and apoptosis, respectively, and for confirmation of involved proteins, Real-Time PCR and western blotting were performed.

Anti-tumor activity of NK-Exo and LAK-Exo was dose- and time-dependent. Their highest activities were observed following 48 hours of incubation with 50 µg/ml exosome (p<0.0001). However, this cytotoxic activity was also seen over a short period of time with low concentrations of NK-Exo (p<0.05) and LAK-Exo (p<0.001). The cytotoxic effect of LAK-Exo on target cells was significantly higher than NK-EXO. The induction of apoptosis by different pathways was time-point dependent. Total apoptosis was 34.56% and 51.6% after 48 hours of tumor cell coculture with 50µg/ml NK-Exo and LAK-Exo, respectively. Significant expression of CASPASE3, P38, and CYTOCHROME C genes was observed in the cells treated with 50 µg/ml NK-Exo and LAK-Exo.

Our study confirmed the antileukemia activity of NK-Exo against AML tumor cells in vitro. Therefore, NK-Exo can be considered as a promising and effective treatment for leukemia therapy.

There is interest in using cytotoxic T lymphocyte antigen-4 (CTLA-4) immunotherapy to treat blood cancers. Unfortunately, patients with acute lymphoblastic leukaemia (ALL) frequently exhibit resistance to treatment and natural killer (NK) cell exhaustion. This study aims to increase the cytotoxic potency of natural killer cells by using CTLA-4 to block the Nalm-6 leukaemia cell line.

In this experimental study, NK cells were purified from the peripheral blood mononuclear cells (PBMCs) of 10 healthy people and assessed by flow cytometry for purity and viability. The purified cells were activated overnight at 37°C and 5% CO2 with interleukin-15 (IL-15, 10 ng/ml) followed by evaluation of expressions of CTLA-4, activating and inhibitory receptors, and the release of interferon gamma (IFN-γ) and granzyme B (GZM B). CTLA-4 expression on NK cells from recurrent ALL patients was also evaluated. Finally, the cytotoxic activity of NK cells was assessed after the CTLA-4 blockade.

The purity of the isolated cells was 96.58 ± 2.57%. Isolated NK cells activated with IL-15 resulted in significantly higher CTLA-4 expression (8.75%, P<0.05). Similarly, CTLA-4 expression on the surface of NK cells from patients with ALL was higher (7.46%) compared to healthy individuals (1.46%, P<0.05). IL-15 reduced NKG2A expression (P<0.01), and increased expressions of NKP30 (P<0.05) and NKP46 (P<0.01). The activated NK cells released more IFN-γ (P<0.5) and GZM B (P<0.01) compared to unactivated NK cells. Blockade of CTLA-4 enhanced the NK cell killing potential against Nalm-6 cells (56.3%, P<0.05); however, IFN-γ and GZM B levels were not statistically different between the blocked and non-blocked groups.

Our findings suggest that CTLA-4 blockage of Nalm-6 cells causes an increase in antitumour activity of NK cells against these cells. Our study also provides evidence for the potential of cancer immunotherapy treatment using blocking anti-CTLA-4 mAbs.

Beta-thalassemia major patients frequently have endocrinopathies. We tried to determine relation between demographic and transfusion factor and endocrinopathies.

Major beta-thalassemia patients (n=114 cases), 3–38 yr of age, entered this study. Female to male ratio was 51/63. Children (less than 20 yr) formed 57% of participants. Information about bone mineral density (BMD) and hormonal and biochemistry blood evaluation including fasting blood sugar (FBS), ferritin, triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), testosterone (males), and estradiol (females) entered data sheet.

Sex and ferritin level showed no significant correlation with above disorders. Age significantly correlated to short stature, diabetes, low BMD at femur and neck (P, 0.031, 0.008, 0.009 and <0.001, respectively). The risk of short stature had increased in 12 yr and older patients 7.71 times than younger patients (P= 0.008). The risk of diabetes had increased in 35 yr and older patients 26.25 times than younger patients (P= 0.03).  The risk of Z-score ≤ -2 in femoral region has increased in 19 yr and older patients 5.84 times than younger patients (P= 0.002). The risk of Z-score ≤ -2 in spinal region has increased in 14 yr and older patients 17 times than younger patients (P= 0.007).

The main factor related with endocrinopathies was age. The correlation between age and short stature, diabetes and low BMD was positive. Therefore, we recommend early monitoring of thalassemia patients (in their late childhood and early teenage) for these complications.

T cells that recognize WT1 peptides have been shown to efficiently eliminate WT1-expressing tumor cells. This study was designed to investigate the feasibility of isolating WT1-reactive T cells from peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with Wilms tumor, and to assess the cytotoxicity mediated by these cells against Wilms tumor cells (WiTu cells).

WT1-reactive T cells were enriched and isolated by stimulating PBMCs with a WT1 peptide pool and interferon-γ capturebased immunomagnetic separation (IMS). Using the lactate dehydrogenase release assay, the in vitro cytotoxicity of the isolated cells and standard chemotherapy was evaluated on WiTu cells.

Higher proportions of WT1-reactive T cells were isolated from patients with Wilms tumor compared to those isolated from HDs. WT1-reactive T cells produced > 50% specific lysis when co-cultured with WT1+ WiTu cells at the highest effector-to-target (E:T) ratio in this study (i.e., 5:1), compared to <23% when co-cultured with WT1- WiTu cells at the same ratio. WT1-reactive T cells showed anti-tumoral activity in a dose-dependent manner and mediated significantly greater cytotoxicity than the non-WT1-reactive fraction of PBMCs on WT1+ WiTu cells. The cytotoxicity of standard chemotherapy was significantly lower than that of WT1-reactive T cells when cocultured with WT1+ WiTu cells at E:T ratios of 2:1 and 5:1.

WT1-reactive T cells can be effectively enriched from the PBMCs of patients with Wilms tumor. Ex vivo generated WT1-reactive T cells might be considered an adoptive immunotherapeutic option for WT1+ Wilms tumors.

Given the high mortality rate of invasive candidiasis inhospitalized pediatric patients, it is crucial to establish a predictive system to achieveearly diagnosis and treatment of patients who are likely to benefit from early antifungal treatment. This study aimed to assess the Candida colonization index, species distribution, and antifungal susceptibility pattern of Candida strains isolated frompediatric patients with high Candida colonization index (CI)

This study was carried out at the Children’s Medical Center inTehran-Iran. In total, 661 samples were collected from 83 patients. The Candida CI wascalculated according to the descriptions of previous studies. The isolates were identified using polymerase chain reaction-based techniques. The Clinical and Laboratory Standard Institute protocol M60 was used to conduct the antifungal susceptibility test.

A colonization index greater than 0.5 was confirmed in 29 cases (58% ofpositive samples) with two children developing candidemia. Candida albicans (n=53,49.5%) was the most common Candida species in patients with CI > 0.5. Except foracute lymphoblastic leukemia, no risk factors were linked to a high index in colonizedchildren (P > 0.05). Twelve isolates (7.01%) were multi-azole resistant with high MICsagainst both isavuconazole and ravuconazole and seven strains (4.09%) wereechinocandins resistant.

In pediatric intensive care units, patients are at risk of fungal infection,particularly candidemia. In this study, more than half of the children with positive yeastcultures had CI > 0.5, and 6.8% developed candidemia.

Programmed death-1 (PD-1) and inducible costimulator (ICOS) are immune checkpoint receptors participating in tumor immune evasion, which counters the activation signal provided through the T-cell receptor ligation. This study aimed to investigate the relationship between the expression of PD-1 and ICOS on mononuclear cells (MNCs) isolated from the peripheral blood of acute myeloid leukemia (AML) patients and their response to induction chemotherapy.

Peripheral blood samples (5 cc) were collected from 56 AML patients at first diagnosis before and after the inductiontherapy regimen for AML. PD-1 and ICOS expression were analyzed in all patients beforeand after the standard induction therapy regimen.

The expression of PD-1 andICOS significantly decreased (66.7 and 16.3 fold, respectively) in AML patients followingchemotherapy compared to its baseline value (P=0.01 and P=0.001, respectively).The expressions of PD-1 and ICOS were significantly different between favorable andpoor risk groups.

Lower PD-1 and ICOS expressions on the surface ofMNCs before induction therapy were associated with a better response to treatments.In addition, PD-1 and ICOS expression on MNCs decreased after induction therapy.

Accumulating evidence has demonstrated that RDW (red blood cell distribution width) may independently predict clinically important outcomes in many populations. However, the role of RDW has not been elucidated in brain death. We conducted this study with the aim of evaluating the predictive value of RDW in brain death.

A retrospective study of seventy-seven of brain death cases during 36 months were evaluated at university hospitals, affiliated in Tehran, Iran. Demographical data include age, sex, BMI and cause of brain death, also laboratory results (red blood cell distribution, mean corpuscular volume, hemoglobin) collected by checklists from patient records. Having the three RDW measurements (days of hospital admission, day of brain death, and day of cardiac arrest) required.

Time interval from hospital admission until brain death was 5.27±4.07. The mean age of brain death cases was 32.65±16.53. The mean RDW values on days of hospital admission, the day of brain death, and the day of cardiac arrest were 14.53±1.98, 15.12±1.93 and 15.18±2.07, respectively. Results of the repeated-measures ANOVA test reveal that RDW level was constantly higher in the traumatic patient group compared to the non-traumatic ones (P=0.008).

The frequency of brain death was high in patients with high RDW values. RDW might be a prognostic biomarker for brain death. More prospective studies with large sample size and long follow-up period should be carried out to determine the prognostic significance of RDW and brain death in future.

In recent years, immunotherapy using chimeric antigen receptor T cells (CAR T cells) has been considered as a novel and promising treatment for some diseases, especially cancer. The CAR T cell production is a multi-step, complex, time-consuming, and costly process. One of the most important steps in production of CAR T cells is expansion of these cells at appropriate numbers for injection. Therefore, the aim of this study was to investigate the methods of expansion for human CAR T cells in ex vivo.

In this study, specifically engineered CAR T cells against the MUC1 tumor antigen were prepared. The cells were then treated with rIL-2, anti-CD3/C28 Dynadeads, and allogeneic PBMC (Rapid expansion protocol (REP)) for 14 days.

The results showed that using anti-CD3/CD28 antibodies in effective ratios; 1: 1 and 1: 3 (bead: cell) along with (IU100) rIL-2 resulted in a 27.5-fold increase in the number of cells. However, the use of rIL-2 alone or allogeneic PBMC eventually resulted in 4.5-fold increase and 9-fold increase, respectively.

Anti-CD3/CD28 in combination with rIL-2 can provide all three signals required for T cell activation and proliferation which can be a suitable alternative to costly and expensive cell proliferation techniques for animal or human CAR T cell studies.

The clinical studies of acute myeloid leukaemia (AML) revealed that antigen escaping variants cause cancer recurrence even after treatment with chimeric antigen receptor (CAR)-T cells that target a single tumour antigen. Due to the heterogeneous expression of antigens on leukaemia blasts, we hypothesized that a novel bispecific CAR, directed to the folate receptor beta (FRβ)-binding single-chain variable fragment (scFv) and an IL3α-binding receptor (CD123) that has more expression in AML blasts, can decrease CAR-T cell exhaustion and increase the efficacy of CAR-T cells to prevent antigen escaping and consequent recurrence of AML.

In this experimental study, the survival, proliferation, and cytolysis of CAR-T cells remains suboptimal even with a costimulatory endodomain. Hence, we designed and constructed a tandem CAR that joins an FRβ and CD123 in the second generation retroviral vector to generate a bispecific tandem CAR (TanCAR-T cell).

TanCAR FRβ-CD123 T cells showed distinct binding to FRβ or CD123 expressing cells. They could lyse the leukaemia cell lines (66.1 ± 11%) comparable to the single CAR-T cells against these determinants. TanCAR FRβCD123 T cells simultaneously engaged FRβ and CD123, which promoted T cell activation in targeting and lysis of the examined leukaemia cell lines. TanCAR-T cell significantly induced interferon gamma (IFNγ) and interleukin 2 (IL-2) production more than single CAR-T cells, which produced a synergistic enhancement of TanCAR FRβ-CD123 T cell function when dual antigens faced simultaneously.

Dual-specific TanCAR FRβ-CD123 T cells showed therapeutic potential to improve AML control by coengaging FRβ and CD123 molecules in a robust, divalent immune system. This strategy may be a useful therapeutic approach in patients with relapsed B-cell malignancies.

Blood malignancies, one of the most common cancers in the world, cause a large number of deaths each year. Many inherited and acquired factors are involved in the development of this disease. Exosomes are a very small model of cells that are secreted by most cells in the body under physiological and pathological conditions. On the other hand, they have found a special place in the treatment of these diseases because of their very small structure and biodegradability. 

This study is a systematic review article. For this study, the electronic databases such as PubMed, Scopus and Web of Science were reviewed and 110 original and review articles were studied from 2000 to 2020. Exosome, blood malignancies and immunotherapy were used as keywords along with a number of other related terms such as tumor microenvironment, acute myeloid leukemia, acute lymphoid leukemia, chronic lymphoid leukemia and multiple myeloma (Exosome AND Leukemia, Leukemia AND Immunotherapy, Exosome AND Cancer, AML AND Exosome) to search in these databases. Finally, 51 sources that related to exosomes and myeloid and lymphoid blood malignancies were used.

The genomic profile of malignant cells and tumor microenvironment changes in the conditions of the disease. The contents of exosomes released by leukemic cells, including anti-apoptotic proteins, various microRNAs, angiogenic agents, heat shock proteins and oncogenes involved in the development of inflammatory phenotype in the target cells, are known as factors involved in the pathogenesis of leukemia. A variety of therapeutic materials such as anti-inflammatory drugs, recombinant proteins, siRNA and the inhibitor of various microRNAs can also be packaged in the exosomes with several ways and used to treat leukemia.

Exosomes derived from malignant cells play the important role in the growth and proliferation, angiogenesis, metastasis, resistance to chemotherapeutic agent, and the escape of cancer cells from the immune system by the modification of tumor microenvironment. The role of exosomes in the creation and development of blood malignancies has been proven. Therefore, using of them will probably be very helpful and promising in the treatment of these disorders with various forms.

Immunotherapy with redirected T cells that express a chimeric antigen receptor (CAR) is a promising prospect in cancer treatment. Most CARs use murine-derived single-chain variable fragments (scFvs) as an antigen targeting moiety, which may lead to host immunogenic responses and engineered T cell disappearance. It seems that development of less immunogenic CARs, such as CARs composed of the camelid variable domain of heavy chain antibodies (VHHs) may likely overcome this obstacle. Here, we improved the expression of the VHH-based anti-MUC1 CAR gene construct using a third generation lentiviral vector in primary human T cells and assessed its effect on antigen specific targeting, activation and cytotoxicity of redirected human T cells.

In this experimental study, we established a second generation novel CAR (VHH-based antiMUC1 CAR) that contained a camelid-derived anti-MUC1 VHH followed by an IgG3 hinge, a CD28 transmembrane domain and signalling endodomains of CD28 and CD3ζ. Next, we constructed lentiviral vectors that contained this CAR gene construct using an optimized transiently virus production method and transduced it into human T cells. Cell surface expression of CAR, cytokine secretion and cytotoxic activity were assessed in the transduced CD3+ T cells.

The transduced T cells had high levels of surface expression of CAR. T cells that expressed anti-MUC1 CAR showed significantly increased secretion of Th1 cytokines, including IL-2, TNF alpha and IFN-γ, as well as cytotoxic activity upon recognition of MUC1 on tumour cells after co-incubation with T47D or MCF-7 (MUC1-positive) compared with A431 (MUC1-negative) or untransduced T cells.

Our results suggested that, given the unique properties of VHHs to prevent immunogenic responses and tonic signalling, our novel VHH-based anti-MUC1 CAR might be effective for clinical purposes in cancer immunotherapy

Familial haemophagocytic lymphohistiocytosis (FHL) is a rare disorder of immune dysregulation. FHL inherited in an autosomal recessive pattern is classified into five subtypes based on underlying genetic defects. Mutations in four genes including PRF1, UNC13D, STX11 and STXBP2 are responsible for FHL2 to FHL5 respectively. The cause of FHL1 is associated with mutations in an unknown gene located at 9q21.3-22. This study aims to report the clinical features and genetic results of nine Iranian patients suffering from -haemophagocytic lymphohistiocytosis. Nine patients (five males and four females) suspected to FHL whose genetic evaluation of PRF1 and STX11 revealed no mutations, were entered the study to investigate UNC13D mutations. Primers were designed to amplify all coding regions and exon-intron boundaries of the gene. PCR products were then sequenced and analyzed by sequence analysis tools including BLAST. The most frequent clinical manifestations observed in the patients were fever and hepatosplenomegaly. In this study, five mutations were detected in UNC13D including four novel mutations (c.1434_1446delACCCATGGTGCAGinsTGGTGCT, c.1933C>T, c.1389+1G>C and c.2091+1G>A) besides to a previously reported deletion (c.627delT). The pathogenicity of the missense mutation was assessed using online prediction tools including SIFT and PolyPhen2. The study results may provide valuable information for genetic counseling especially for those who have a history of immunodeficiency diseases in their family and can be used for prenatal diagnosis.

Chronic granulomatous disease (CGD) is a rare genetic disorder of neutrophil activity, resulting in increased rate of recurrent infections with catalase–positive bacteria and fungi, as well as various autoimmune diseases such as sarcoidosis, rheumatoid arthritis, and discoid and/or systemic lupus erythematosus. Few reports have reported lupus erythematosus (LE) in patients with X–linked CGD (XL-CGD) and carriers, and very few in autosomal recessive CGD (AR-CGD). Here, we present 5 patients with CGD developing LE at different ages to emphasize on the importance of appropriate follow–up and treatment in patients with CGD with clinical signs and symptoms of autoimmune diseases and even in those with negative serologic results.

Primary immunodeficiency (PID) is a group of more than 400 distinct genetic disorders affecting both children and adults. As signs and symptoms of PID are usually heterogeneous and unspecific, diagnosis and follow-up of these patients can be challenging based on the available human resources and laboratory facilities.In order to reach a distinct national protocol and due to little evidence to guide appropriate or univer-sal guidelines to improve the current status of management of the disease, the Iranian PID network designed a consensus appropriate for regional resources. This review summarizes this PID guideline based on the importance of different clinical complications and the level of medical authority visiting those at the first line. Moreover, for each complication, appropriate interventions for improving ap-proach are mentioned.

Recently, Long noncoding RNAs (lncRNAs) have been described as regulatory factors for several biological mechanisms through regulating the gene expression. Among them the TNF and HNRNPL related immunoregulatory (THRIL) lncRNA may be involved in the pathogenesis of immune-related and inflammatory disease through controlling the expression of the tumor necrosis factor-alpha (TNF-α) expression. In this case-control study, we investigate the THRIL expression in blood 25 samples of de novo acute myeloid leukemia (AML) cases (10 females and 15 males, mean age±SD: 35.1±3.2 years) in comparison to 50 healthy age and sex matched controls (21 females and 29 males, mean age±SD: 34.9± 3.1) using real-time quantitative reverse transcription-PCR (qRT-PCR) in order to explore any association between THRIL and AML. Our results revealed that there was no significant difference in the expression level of THRIL lncRNA between AML patients and healthy individuals (p=0.2, 95% CI=-0.129-28.35). In addition, there was no significant association between male subgroup and THRIL expression as well as females (p=0.08, 95% CI=-0.197-19.251, p=0.4, 95% CI=-0.185-12.041, respectively). In comparison between control group and FAB classification subtypes of AML patients, there was not any significant association. In conclusion, our study showed that THRIL cannot be used as an informative biomarker for AML diagnosis, however, our results need to be clarify by evolution of more cases.

Beta thalassemia major (BTM) and its treatment by hematopoietic stem cell transplantation (HSCT) may have deleterious effects on the endocrine systems. We assessed endocrine complications of HSCT in pediatric patients for 3 months.
In 20 (6 female) pediatric major thalassemic patients (mean age of 10.8 ± 3.9 years old), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), T4, T3, thyroid-stimulating hormone (TSH), IGF-1, testosterone (in males) or estradiol (in females) were measured as a batch at the Endocrinology and Metabolism Research Center (EMRC) of Tehran University of Medical Sciences (TUMS) laboratories before HSCT and 1 and 3 months afterwards. The cosyntropin test for all and the clonidine test for short stature patients was conducted before HSCT.
Before HSCT, delayed puberty and hypogonadotropic hypogonadism was found in 10% and 20% of patients, respectively. GH deficiency, low IGF1 and short stature was found in 25%, 55% and 40% of patients, respectively. Hypocortisolism, hypothyroidism and panhypopituitarism was found in 15%, 10% and 15% of patients, respectively. Prevalence of hypogonadotropic hypogonadism, low IGF1, hypothyroidism and panhypopituitarism was found in 20%, 40%, 10% and 10% of patients after 3 months, respectively (delayed puberty and short stature prevalence do not change after 3 months). HSCT caused lower T3 and estradiol and higher TSH. Corticosteroid users (15) had higher GH and lower T3 and testosterone or estradiol. Ferritin had a significant (negative) correlation with (before) prolactin and a significant correlation with T3 and T4 after HSCT. Age and acute graft-versus-host disease (GVHD) had no significant effect.
Considering the small sample size and short duration of the study, it is difficult to reach any conclusion however it seems HSCT does not appear to have an overall positive or negative effect on prevalence of pituitary- hypothalamus axis disorders in pediatric thalassemic patients in 3 months.

In order to clarify the role of microRNAs (miRNA) in megakaryocyte differentiation, we ran a microRNA microarray experiment to measure the expression level of 961 human miRNA in megakaryocytes differentiated from human umbilical cord blood CD133 cells.
In this experimental study, human CD133 hematopoietic stem cells were collected from three human umbilical cord blood (UCB) samples, and then differentiated to the megakaryocytic lineage and characterized
by flow cytometry, CFU-assay and ploidy analysis. Subsequently, microarray analysis was undertaken followed by quantitative polymerase chain reaction (qPCR) to validate differentially expressed miRNA identified in the microarray analysis.
A total of 10 and 14 miRNAs were upregulated (e.g. miR-1246 and miR-148-a) and down-regulated (e.g. miR- 551b and miR-10a) respectively during megakaryocyte differentiation, all of which were confirmed by qPCR. Analysis of targets of these miRNA showed that the majority of targets are transcription factors involved in megakaryopoiesis.
We conclude that miRNA play an important role in megakaryocyte differentiation and may be used as targets to change the rate of differentiation and further our understanding of the biology of megakaryocyte commitment.

I and my colleagues in the Council for Development of Stem Cell Sciences and Technologies are proud to announce that stem cells sciences and regenerative medicine (SCRM), as a productive field of knowledge, is developing at a very rapid pace in our country, with the dedicated efforts of our prominent professors, young and passionate researchers, emerging knowledge-based companies and futuristic decision makers. In view of our achievements in this area of science, we are going tohost the second scientific gathering “The 2nd National Festival and International Congress on Stem Cells and Regenerative Medicine” in Tehran in July 2017 with the participation of all students, scholars, researchers and other stakeholders in the field.
Stem cell sciences and technologies have growingly attracted the attention of university students, scientists and researchers. The advancements of SCRM as well as investments recently made by the major companies in this field, have paved way for hopeful future of lasting treatment for refractory and terminal diseases. These developments show that SCRM can play a significant role in future of the heath market. Hence, mastering this strategic knowledge can further boost the scientific status of our country at international levels.
Relying on the capabilities of its graduated scientists, Islamic Republic of Iran has launched extensive efforts to localize thisknowledge during the past decade. These efforts have fortunately borne fruit and boosted the position of our country at a par with other advanced countries. The 2nd National Festival and International Congress on Stem Cells and Regenerative Medicine provides an opportunity for the general public to become familiar with the concepts of this strategic knowledge and for our scientists in the field to present and promote their ideas in a way which would be commercially viable and increase the competitiveness in the market.
This event also gives industries and investors to pick the most productive ideas in the field and help further developing and making them accessible to the public. It also opens window of hope for patients with refractory diseases. In addition, young students and entrepreneurs will grasp benefit from the business environment provided in this event to join this fast growing technology.
I would like to use this opportunity to invite all decision and policy makers in the health sector, professors, researchers and students in the medical, basic, technical and engineering sciences, and also, owners of industries and investors in the field of pharmaceuticals and medical equipment as well as all other relevant stakeholders to attend this scientific meeting. Additionally, to our international audience, I would like to invite them to visit the warm, welcoming, vibrant city of Tehran and to enjoy the scientific program of our festival.
Dr. Amir Ali Hamidieh
General Secretary of Festival

Thalassemia is a chronic, inherited blood disorder, which in its most severe form, causes life-threatening anemia. Thalassemia patients not only engage with difficulties of blood transfusion and iron chelating therapy but also have some social challenges and health threatening factors. There are some reports on quality of life in thalassemia patients around the world from southeast of Asia to Italy in Europe and United States. In this study, we tried to evaluate and compare Health Related Quality of life (HRQoL) and the health utility in beta thalassemia major patients receiving different types of iron chelators and living in different socio-economical situations.
Subjects and EQ-5D-3L accompanied by a Visual Analogue Scale (VAS) questionnaire was used. The respondents were patients with beta thalassemia major that were at least 12 years old selected from 3 provinces of Sistan-Blouchestan, Fars and Mazandaran. Comorbidities including heart complication, Diabetes Mellitus and Hepatitis and also types of iron chelators (oral, injection, combination of both) were also asked. Cross tab and ANOVA analysis conducted to evaluate each dimension score and health utility differences between provinces, iron chelation methods, comorbidities, age group and gender.
528 patients answered the questionnaires. The health utility of patients that received oral iron chelator were 0.87 ± .01 for oral iron chelators versus 0.81 ± .01 for injection dosage form (p This study suggests that the quality of life of beta thalassemia major patients is dependent on type of iron chelation treatment which they received, the gender they have, the comorbidities they suffer and socio-economical situations they live in.

Isolated extramedullary relapse of chronic myelogenous leukemia (CML) after allogeneic stem cell transplant is rare. There is a case report of a child who developed a granulocytic sarcoma of the maxillary and sphenoid sinuses and lumbosacral spinal cord mass 18 months after allogeneic bone marrow transplant for CML. He was presented with per orbital edema and neurological deficit of lower extremities and a mass lesion was found on spinal cord imaging. No evidence of hematologic relapse was identified at that time by bone marrow histology or cytogenetic. The patient died 1 month later with a picture of pneumonia, left ventricular dysfunction and a cardiopulmonary arrest on a presumed underlying sepsis with infectious etiology. Granulocytic sarcoma should be considered in the differential diagnosis of mass lesions presenting after allogeneic bone marrow transplantation for CML, even if there is no evidence of bone marrow involvement.

Leukocyte adhesion deficiency type I (LAD-I) is a rare, autosomal recessive inherited immunodeficiency disease. LAD-I is caused by mutations in the ITGB2 gene and characterized by recurrent severe bacterial infections, as well as impaired wound healing with lack of pus formation. In this study, we investigated ITGB2 gene mutations in 12 patients and their parents. Genomic DNA was extracted from whole blood samples. All coding regions of the ITGB2 gene were amplified using PCR and followed by direct sequencing. Genetic analysis revealed 12 different homozygous mutations, including six missense (c.382G>A, c.2146G>C, c.715G>A, c.691G>C, C.1777C>T and new C.1685G>A), two new nonsense (c.1336G>T and c.1821C>A), three-frame shift (c.1143delc, c.1907delA and new c.474dupC) and a splice site (c.1877+2T>C). Flow cytometry analysis of CD11/CD18 expression on neutrophils revealed defect in CD18 in all twelve cases (1.4% to 42%), CD11a in ten cases (0.1% to 26.7%), CD11b in nine cases (1.2% to 58.8%), and CD11c in all cases (0% to 18.1%). The patients’ parents were both heterozygous carriers. Our findings showed four new mutations in the ITGB2 gene. These results can be used for decisive genetic diagnosis, genetic counseling, as well as prenatal diagnosis for all patients who are suspended to LADI.

Cox proportional hazard model is a popular choice in modeling the survival data, but sometimes proportionality assumption is not satisfied. One of the tools for handling the non-proportional effects is the multiplicative-additive model named “Cox-Aalen model”. Recently these flexible regression models developed for competing risks setting. The aim of this paper is showing the application of the multiplicative-additive model in competing risks setting on real bone marrow transplantation (BMT) data when the proportionality assumption is violated. The data was from a retrospective study on class III thalassemia patients who undergo hematopoietic stem cell transplantation (HSCT) in BMT ward of Shariatei Hospital, Tehran, Iran. The neutrophil engraftment time as the early outcome of HSCT on37 patients who received mesenchymal stem cell infusion (MSC group) compared with 50 patients who did not. We fit the standard proportional models and flexible Cox-Aalen model in the sub distribution hazards. By day 30 after transplantation, the cumulative incidence of neutrophil recovery was 97% (95%CI: 89%-100%) and 76%(95%CI: 64%-88%) in MSC and control group, respectively. Based on the Cox-Aalen model for cumulative incidence function, the MSC infusion had a significant delay effect on neutrophil engraftment (P=.044). In patients who did not neutrophil recovery immediately after HSCT, those who received MSC had faster recovery. Cox-Aalen model provides more accurate statistical description for time-varying covariate effects. There is a positive effect of MSCs on the neutrophil recovery, however further study on the advantages and disadvantages of MSCs are needed.

Thalassemia along with hematopoietic stem cell transplantation (HSCT) can lead to major oxidative stress. Vitamins A and E are antioxidants which protect membrane from lipid peroxidation. We sought to determine for the first time, whether vitamins A and E supplementation is efficacious in maintaining or increasing plasma level of these vitamins in thalassemic children undergoing HSCT. A cross-sectional study was performed on 50 children with β-thalassemia major hospitalized for HSCT. Patients took a daily multivitamin. Plasma vitamins A and E levels were measured at four different times: on admission, HSCT day (day 0), day 7 and day 14 after HSCT. Plasma vitamin A and E were abnormal on admission in most patients (62.0% and 60.0% respectively). Ratio of patient with normal to abnormal plasma level of the vitamins improved from baseline to a peak on day 7 then deteriorated afterward until day 14. There was an increasingly positive correlation between daily oral intake and plasma vitamin A at different times, but plasma vitamin E showed inverse correlation at first which tended towards no correlation subsequently. In multivariate analysis, supplementation significantly changed plasma level of vitamin A at different measurement times (P=0.001) within study subjects. But, plasma level of vitamin E showed no significant difference (P=0.2). Our findings suggest that oral supplementation could have beneficial effects due to increasing plasma vitamin A level and preventing plasma vitamin E depletion.

Severe congenital neutropenia (SCN) is a rare primary immunodeficiency disease. Different genes are found to be associated with SCN, including ELA2, HAX1, WAS, GFI1, G-CSFR and G6PC3. The aim of this study was to find different gene mutations responsible for SCN in Iranian patients. Twenty-seven patients with SCN referred to Immunology, Asthma and Allergy Research Institute during a five year priod 5 years (May 2007 and May 2012), were included in this study. Neutropenia related exons and flanking regions of ELA2, HAX1, WAS, GFI1, G-CSFR and G6PC3 were amplified by PCR and the sequences were analyzed. The results showed different mutations including 4 ELANE mutations, 11 HAX1 mutations and 2 G6PC3 mutations. None of the patients had GFI1 mutation and also one mutation was found in G-CSFR in a patient with ELANE mutation. Ten patients had unknown genetic diagnosis which was compatible with other studies. According to these results, most of the patients showed HAX1 mutations and this finding which significantly differed from other reports, might be related to differences in Iranian ethnicity and also in high rate of consanguineous marriages in Iran.

Despite achievement to complete remission (CR) with current treatments and new multiple chemotherapeutic agents in Acute Lymphoblastic Leukemia (ALL) patients, the majority of them still relapse during long-term follow-up. The use of post- remission therapy will reduce early relapse in these cases, but the best option is still debatable.Patients and In this retrospective review, we assessed the outcome of allogeneic hematopoietic stem cell Transplantation (HSCT) in ALL patients treated in our center. All cases received cyclophosphamide and busulfan as conditioning regimen, cyclosporine A and methotrexate for graft versus host disease prophylaxis (GVHD) and trimethoprim/sulfamethoxazole, acyclovir and fluconazol as prophylaxis of bacterial / viral and fungal infections. From March 1991 till August 2011, 446 ALL patients with a median age of 20 (range: 2 -53) years old underwent allogeneic HSCT. The male to female ratio was 300/146. At the time of transplantation 63 % of cases were in first CR, 23 % in second CR and 6% in third CR. Thirty eight (9%) patients were transplanted in primary induction failure or relapse. Sources of hematopoietic stem cell included peripheral blood (n=412, 92.3%), bone marrow (n=23, 5.1%), cord blood (n=8, 1.7%) and peripheral blood with bone marrow (n=3, 0.9%). Almost 93.2% of patients received stem cells from their HLA- identical siblings. HLA-mismatched sibling or other relatives, HLA-matched other relative and HLA-mismatched unrelated donors were 3.4%, 2% and 1.4%, respectively. Female patients received stem cells from 16% of female and 17% of male donors. Male patients received stem cells from 26% of female and 41% of male donors. The median time of neutrophil recovery was16 (range: 6-58) days and platelet recovery was 12 (range: 9-43) days. Relapses occurred in 106 (24%) patients. 18-month LFS and OS were 58.9% (SE: 2.6%) and 68.1% (SE: 2.5%), respectively. According to these results, allogeneic HSCT as a post- remission therapy can improve OS and DFS in ALL patients with a reduction in relapse rate