Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 15 4 2021 10 14 206 212 Mohsen Esfandbod Department of Clinical Hematology and Bone Marrow Transplantation, Vali-e-Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran Mina Naderi Department of Internal Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran Azadeh Sadat Naseri Department of Cardiology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran Ayat Ahmadi Knowledge Utilization Research Center, Tehran University of Medical Sciences, Tehran, Iran Mohammadtaghi Noroozi Department of Internal Medicine, Medical Oncology-Hematology Ward, Sina Hospital, Tehran University of Medical Science (TUMS), tehran, iran Saeid Sadeghi Joni Department of Radiology, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran 2020 05 23 2020 09 10 Background: Trastuzumab is an efficient monoclonal antibody used in the treatment of Her2-positive breast cancer. Despite its prominent effect on Her2-positive patients’ disease-free Survival. Trastuzumab-induced cardiotoxicity is still one of the main challenges.  Angiotensin-converting enzyme inhibitors (ACE inhibitors) are one of the most potent agents used in heart failure, which also showed confirmed cardioprotective effects against anthracycline and doxorubicin. We aimed to assess the cardioprotective effects of Carvedilol in a randomized clinical trial study. Materials and Methods: sixty non-metastatic Her-2 positive patients (30 cases; 30 controls) were entered to the study via a simple randomization method. Carvedilol was administered for the patients with the starting dose of 3.125 mg twice a day and started 7 days before trastuzumab administration. The dose has been increased in a three-week period to reach 12.5 mg twice a day and continued until the end of therapy. All the patients underwent an echocardiography after receiving Adriamycin and Cyclophosphamide in order to measure basal Ejection Fraction (EF) and Pulmonary Artery Pressure (PAP). Each patient underwent a follow-up echocardiography in 3,6,9 and 12 months after initiation of the treatment. Finally, all the patients went through the last episode of echocardiography 1 month after the end of treatment. All the Measured PAP and EF has been recorded and analyzed Results: EF and PAP changes for both groups had no significant changes during the course of treatment with Trastuzmab (p-value = 0.628 and p-value = 0.723, respectively). 7 patients in the intervention group and 2 patients in the control group presented with EF decrease. Also, 8 patients in the intervention and 9 patients in the control groups showed PAP increase. Conclusion: According to our results, in patients with HER2-positive breast cancer treated with trastuzumab, Carvedilol showed no significant protective effect on trastuzumab-induced cardiotoxicity. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1346 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1346/886

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 15 4 2021 10 14 213 220 EN Younes Sadeghi-Bojd Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Naser Amirizadeh Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Arezoo Oodi Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran 2020 05 10 2020 08 31 Background: The D antigen is a subset of Rh blood group antigens involved in the hemolytic disease of the newborn [HDFN] and hemolytic transfusion reaction [HTR]. The hybrid Rhesus box that was created after RH gene deletion, was known as a mechanism of the Rh-negative phenotype. Hybrid marker identification is used to confirm the deletion of the RHD gene and to determine zygosity. This study aims to detect this marker in Rh-negative and weak D phenotype blood donors of the southeast of Iran. Materials and Methods: The molecular analysis of the hybrid Rhesus box was performed on the 200 Rh-negative blood donors in Sistan and Baluchestan province, southeast Iran. The presence of alleles responsible for the D variants was assessed by DNA sequencing in 26 weak D phenotype donors. Results: Of the 200 Rh-negative blood samples, 198 samples were homozygous (99%), and two samples were heterozygous (1%). Heterozygous samples had RHD*01N.73 allele and the RHD*01N.18 allele. Of the 26 samples with weak D phenotype, 16 partial DLO (61%), 4 partial DBT1 (15.3%), 2 partial DV type 2 (7.7%), 1 weak D type 1, 1 weak D type 4.2.3, 1weak D type 105 and 1 RHD (S103P) (4%) were determined. Conclusion: Since RHD gene deletion is the main mechanism of the Rh-negativity in Sistan and Baluchestan provinces, a hybrid Rhesus box marker can be used in resolving RhD typing discrepancies by RHD genotyping methods. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1335 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1335/887

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 15 4 2021 10 14 221 229 Kawinthra Khwanraj Department of Anatomy, Faculty of Science, Mahidol University, Bangkok 10400, Thailand Permphan Dharmasaroja Department of Anatomy, Faculty of Science, Mahidol University, Bangkok 10400, Thailand 2020 05 09 2021 05 20 Background The protein kinase B/mammalian target of the rapamycin (Akt/mTOR) pathway is one of the most potent prosurvival signaling cascades that is constitutively active in neuroblastoma. The eukaryotic translation elongation factor-1, alpha-2 (eEF1A2) protein has been found to activate the Akt/mTOR pathway. However, there is a lack of data on the role of eEF1A2 in neuroblastoma. The present study investigated the effect of eEF1A2 silencing on the viability of neuroblastoma cells and its possible signaling. Materials and Methods: Human SH-SY5Y neuroblastoma cells were transfected with small interfering RNA (siRNA) against eEF1A2. After 48 h of transfection, cell viability was assessed using an MTT assay. The mRNA expression of p53, Bax, Bcl-2, caspase-3 and members of the phosphoinositide 3-kinases (PI3K)/Akt/mTOR pathway was determined using quantitative real-time RT-PCR (qRT-PCR). The protein expression of Akt and mTOR was measured using Western blot analysis. Results: eEF1A2 knockdown significantly decreased the viability of neuroblastoma cells. No significant changes were observed on the expression of p53, Bax/Bcl-2 ratio, and caspase-3 mRNAs; however, the upregulated trends were noted for the p53 and Bax/Bcl-2 ratio. eEF1A2 knockdown significantly inhibited the phosphorylation of both Akt and mTOR. Almost, all of the class I (PIK3CA, PIK3CB, and PIK3CD) and all of the class II PI3K genes were slightly increased in tumor cells with eEF1A2 knockdown. In addition, a slightly decreased expression of the Akt2, mTORC1, and mTORC2 was observed. Conclusion: eEF1A2 knockdown induced neuroblastoma cell death, in part through the inhibition of Akt and mTOR, suggesting a potential role of eEF1A2 as a molecular target for neuroblastoma therapy. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1329 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1329/888

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 15 4 2021 10 14 230 238 EN Minoo Ahmadinejad Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Massoumeh Shahbazi Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Azita Chegini Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran 2020 04 26 2021 09 11 Background: Heparin-induced thrombocytopenia (HIT) is a serious adverse drug reaction. HIT diagnosis needs an algorithmic approach including clinical evaluation and laboratory tests (screening and confirmatory). Few studies have been conducted on HIT in Iran, and most existing research has been general and based on clinical evaluations alone. The present study was conducted to determine the prevalence of HIT among cardiac surgery patients using an algorithmic approach. Materials and Methods: A cross-sectional study was carried out over a period of 10 months, at Modares Hospital (Tehran, Iran) on 92 patients who were candidates for cardiac surgery. For the clinical evaluation, the 4Ts scoring system was used; in cases with 4Ts scores ≥4, a laboratory evaluation of anti-PF4/heparin antibody (Ab) was performed by enzyme-linked immunosorbent assay (ELISA) and a HIPA test too as a functional confirmatory method. The patients with 4Ts scores ≥4 who were ELISA positive (OD ≥0.2) and HIPA positive were taken as a definite case of HIT. Results: Of the 92 patients who had undergone cardiac surgery, 14 (15%) had 4Ts scores ≥4. Anti- PF4/heparin Ab was detected in eight patients using the ELISA and in six patients using the HIPA. Ultimately, definite HIT was confirmed in five of the patients. Conclusion: The prevalence of HIT was 5.4% among the cardiac surgery patients assessed in the present study. To the researchers’ knowledge, this is the first time that HIT has been evaluated in Iran using a comprehensive algorithmic approach including clinical history-taking and both immunological and functional laboratory tests, and the findings showed a slightly higher HIT frequency in this single-center study in comparison with the other studies carried out in other countries.   https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1324 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1324/889

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 15 4 2021 10 14 239 248 EN Farzaneh Ashrafi Hematology Oncology Division, Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Shahrzad Shahidi Nephrology Division, Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Valiollah Mehrzad Department of Clinical Oncology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Mojgan Mortazavi Isfahan Kidney Disease Research Center, Isfahan, Iran Sayyiedh Forough Hosseini Department of Oncology, Hematology, Cancer Prevention Research Center, Isfahan University of Medical Sciences, Isfahan, Iran 2020 08 02 2020 12 19 Background: One of the important causes of mortality and morbidity in kidney transplanted patients is Post Transplant Lymphoproliferative Disease (PTLD), which is due to immunosuppression therapy and viral activity. It seems that Rapamycin, with dual antineoplastic and immunosuppressive effects, may have a pivotal role in the treatment of PTLD patients and preserving transplanted kidneys. Methods and Materials: Twenty patients with PTLD were enrolled.  Immunosuppressive therapy was reduced or ceased, and Rapamycin was initiated at the time of PTLD diagnosis. We evaluated the effects of switching immunosuppressive drugs to Rapamycin on graft status, the response of tumor, and 6, 12 months, and 5-year survival in patients. Results: PTLD remission was achieved in 14 patients, while six patients died; no relapse was detected in recovered patients. The median of PTLD free time was 25 months, and the mean overall survival in patients with PTLD treated by Rapamycin was 84.8 (95% CI=61.3-108.23).The five-year survival rate was 67%, 12 months survival was 73.8%, and six months' survival was 80%. The response rate to Rapamycin and immunosuppression reduction alone was 46.6%. Four out of 13 Diffuse Large B-Cell Lymphoma patients achieved a complete response just only after the reduction of immunosuppressive drugs and the consumption of Rapamycin. Conclusion: The present study demonstrated the effectiveness of conversion from immunosuppressive medication, particularly of Calcineurin inhibitors to Rapamycin in PTLD patients. However, more research is needed to confirm the Rapamycin effect on patients with PTLD. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1404 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1404/890

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 15 4 2021 10 14 249 254 EN Nishit Gupta Department of Haematology, BLK Superspeciality Hospital, Delhi, India, 110005 Aditi Mittal Department of Haematology, BLK Superspeciality Hospital, Delhi, India, 110005 Rajan Duggal Department of Histopathology, BLK Superspeciality Hospital, Delhi, India, 110005 Tina Dadu Department of Haematology, BLK Superspeciality Hospital, Delhi, India, 110005 Amit Agarwal Department of Medical Oncology, BLK Superspeciality Hospital, Delhi, India, 110005 Anil Handoo Department of Haematology, BLK Superspeciality Hospital, Delhi, India, 110005 2020 05 14 2021 10 09 Hodgkin lymphoma variant of Richter’s transformation (HL-RT) is a rare event, occurring in < 1% chronic lymphocytic leukemia (CLL) cases, of which, in < 10% cases, HL is the first finding leading to a diagnosis of CLL that co-exists simultaneously. Here we report a 60 years old male patient who presented with an outside diagnosis of lymphocyte-rich classical HL. On evaluation, he had only B-symptoms in the form of low-grade fever and weight loss. Peripheral smear revealed mild leukocytosis with an absolute lymphocytosis and a few smudge cells. Bone marrow (BM) aspirate and biopsy exhibited diffuse infiltration by a small cell, low grade, Non-Hodgkin’s lymphoma with no immunohistochemical evidence of HL. Flow cytometry performed on BM was consistent with classical immunoprofile of CLL. Meanwhile the lymph node received for review revealed diffuse effacement of nodal architecture by small mature lymphocytes with immunoprofile of CLL expressing CD20, CD5, and CD23. Interspersed between these cells, were a few eosinophils along with classical Reed Sternberg cells, expressing CD30, MUM-1, CD15, and dim PAX-5, with a surrounding rosette of T-Cells highlighted by CD3 and PD-1 and negative for CD45, CD20, and EBV immunohistochemistry. Fluorodeoxyglucose positron emission tomography (FDG-PET) scan revealed hepatosplenomegaly with multiple supra/infra diaphragmatic lymph nodes. So, a final diagnosis of HL-RT in CLL was considered. The patient is currently doing well after the first cycle of ABVD chemotherapy. HL-RT occurring in CLL is a rare event with heterogeneous clinical presentation, morphology, clonal origin, disease course, prognostic features, and survival. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1339 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1339/891

Tehran University of Medical Sciences International Journal of Hematolog/Issn> 16 3 2022 07 09 151 156 Saeed Mohammadi Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran 2) Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran 3) Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Fatemeh Aghabozorg Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Sahar Balagholi Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Shirin Ferdowsi Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Shahin Sharifi Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Peyman Eshghi Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran AND Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children`s Health ,Shahid Beheshti University of Medical Sciences, Tehran, Iran 2021 05 23 2021 08 12 Background: A declining need for red blood cells coupled with strengthening demand for plasma-derived medicines has led to a strong focus on moving whole blood donors to plasmapheresis. The purpose of this study was to evaluate the four-year policies of the Iranian Blood Transfusion Organization (IBTO) in terms of plasmapheresis recruitment of first-time donors and its effect on plasmapheresis outcome.   Materials and Methods: Plasmapheresis data related to 16 centers from 2016 to 2019 was obtained from IBTO software. This information includes; (1) blood donation number, (2) plasmapheresis donation number, (3) number of plasmapheresis donors, (4) plasmapheresis donor demographic data, (5) plasmapheresis donor status, (6) frequency of plasma donation for each donor, (7) volume of plasma and (8) the prevalence of transfusion-transmissible infections (TTIs) in plasmapheresis donors. Results: The result of this study demonstrated that plasmapheresis collection centers have recruited 85,515 (91%) first-time and 8,595(9%) regular and repeated donors from 2016 to 2019 years. Plasmapheresis to blood donation index was increased from 0.2% in 2016 to 4.9% in 2019. The mean donation number was 2 times per year. The trend of the yearly Whole Blood Donation (WBD) Index decreased from 26.69 to 24.11/1000 for the general population. The total volume of collected source plasma was 49,203 liters during this period. However, 46,000 liters of recovered plasma were decreased due to less WBD. Furthermore, the results indicated that the prevalence of HCV was significantly higher in first-time donors compared to repeated and regular donors (P = 0.000). Conclusion: It is concluded that during four years, the net volume of plasma did not increase and plasmapheresis led to reducing WBD in our country. Moreover, first-time plasmapheresis donors can be associated with challenges such as increasing screening costs and compromising the safety of plasma resources. Therefore IBTO decided to stop the project and focus on its main role to prepare safe and sufficient blood components through WB collection and also single donor platelet and concurrent plasma by plateletpheresis.   https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1641 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1641/940

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 16 3 2022 07 09 157 163 Roya Irani Department of Biology, Islamic Azad University, Tabriz Branch, Tabriz, Iran Masoud Maleki Department of Biology, Islamic Azad University, Tabriz branch, Tabriz, Iran