Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 16 4 2022 10 15 189 197 EN Eucario Leon Rodriguez Hematopoietic Cell Transplantation Program, Department of Hematology and Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico Monica Rivera Franco Hematopoietic Cell Transplantation Program, Department of Hematology and Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico 2020 09 03 2020 10 29 Background: Conditioning regimens are critical for allogeneic hematopoietic cell transplantation (allo-HCT). After unfavorable results using BuCy2 at the beginning of our HCT Program, a restructuring was made with the consequent development of a modified HCT method including a reduced conditioning regimen. The objective of this study was to describe the outcomes using Reduced BuCy2 (rBuCy2) in allo-HCT. Materials and Methods: Data from 38 consecutive patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who underwent allo-HCT conditioned with rBuCy2 in a 21-year period were retrospectively analyzed. Results: Most patients were males (53%) and the median age was 35 years. The most common disease was myelodysplastic syndrome (55%). Toxicity grades III-IV were observed in 44%; and acute and chronic graft-versus-host disease were observed in 26% and 34%, respectively; the median follow-up was 26 months; 30-day non-relapse mortality (NRM) was 3%, and 1 and 2-year NRM were 8%. Ten-year overall survival (OS) was 60%, and 86%, for AML and MDS, respectively. Conclusion: Our rBuCy2 maintains a myeloablative effect, along with immunosuppression for fast engraftment and more importantly, this regimen reduces grades III-IV acute GVHD and NRM in allo-HCT and improves the OS and it appears to be an option for low and middle-income countries https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1423 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1423/946

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 16 4 2022 10 15 250 263 Atousa Haghi 1) Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran 2) Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 3) Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center. Tehran University of Medical Sciences, Tehran, Iran Mahnaz Mohammadi Kian 1) Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran 2) Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Mahdieh Salemi 1) Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran 2) Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran Mohammad Reza Eghdami 1) Department of Social Sciences, University of Guilan, Rasht, Iran 2) Department of Biological Anthropology, Research Institute of Guilan Studies, University of Guilan, Rasht, Iran Mohsen Nikbakht Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran 2) Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran 2021 02 13 2022 01 11 Autophagy is an intracellular self-degradative process that delivers cytoplasmic constituents to the lysosome. Autophagy plays a critical role in balancing sources of energy in response to harsh conditions and nutrient deprivation. Autophagy allows cells to survive in harsh condition and also serve as a death mechanism. Any dysregulation in autophagy signaling may lead to several disorders. Autophagy has been proposed to explain chemotherapy resistance in acute myeloid leukemia (AML). This signaling pathway can either act as a tumor suppressive function or chemo-resistance mechanism. Conventional chemotherapy drugs enhance apoptosis and indicate clinical benefit, but in some cases, relapse and chemotherapy resistance are observed. In leukemia, autophagy may promote cell survival in response to chemotherapy drugs. Therefore, new strategies by inhibiting or activating autophagy may find a broad application for treating leukemia and may significantly enhance clinical outcomes. In this review, we discussed how dimensional role of autophagy in leukemia.  https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1547 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1547/955

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 16 4 2022 10 15 198 208 Jitendra Lakhani Department of Medicine, SBKSMI&RC, Sumandeep Vidyapeeth deemed to be university, Vadodara, Gujarat, India Roop Gill Department of Medicine, SBKSMI&RC, Sumandeep Vidyapeeth deemed to be university, Vadodara, Gujarat, India Deep Mehta Department of Medicine, SBKSMI&RC, Sumandeep Vidyapeeth deemed to be university, Vadodara, Gujarat, India Sucheta Lakhani Department of Microbiology, SBKSMI&RC, Sumandeep Vidyapeeth deemed to be university, Vadodara, Gujarat, India 2020 09 13 2021 05 15 Background: Spleen has been found to be the earliest organ involved in sickle cell disease (SCD) patients with variable manifestations in different geographical regions. It usually undergoes autosplenectomy by adolescence but in countries like India, the course of the disease and splenic manifestations are different. And here we aim to study these differences and the relationship between spleen size and fetal hemoglobin (HbF) and various splenic complications in our patients with sickle cell disease. Materials and Methods: This is an observational study of 62 adult patients with sickle cell disease admitted in our prestigious institute in the northwestern part of India, mostly hailing from the tribal population. The clinical and ultrasonographic methods have been used to identify splenomegaly and spleen size and prevalence have been calculated. The correlation coefficient has been calculated between fetal hemoglobin, sickle hemoglobin, and spleen size. Results: The analysis done revealed that 77.4% of patients had abnormal spleen with high average HbF(14.9±5.0) values compared to those who had normal spleen(12.12±4.1). Only 2 patients were found to have no spleen and 3.3% had splenic infarct. All patients with splenomegaly had anemia, 51.6% of patients were in sickle cell crisis and 22.5% were having infections. We also found a weak but positive correlation between spleen size and HbF. Conclusion: This study revealed the persistence of the spleen, the high prevalence of splenomegaly in the Indian adult population with sickle cell disease, and higher levels of fetal hemoglobin, the exact reason for which is still a subject of speculation that needs research. But this paper provides clear evidence of different natural courses of SCD in India. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1429 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1429/947

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 16 4 2022 10 15 209 216 Mohammad Biglari Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran Hosein Kamranzadeh Foumani Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy Tehran University of Medical Sciences, Tehran, Iran Maryam Bagherian Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy Tehran University of Medical Sciences, Tehran, Iran Bahram Chahardouli Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy Tehran University of Medical Sciences, Tehran, Iran Ardeshir Ghavamzadeh Cancer & Cell Therapy Research Center, Tehran University of Medical Sciences, Tehran, Iran 2022 02 24 2022 09 06 Background: Hairy cell leukemia (HCL) is a distinct lymphoproliferative disorder with unique circulating lymphocyte morphology. It is now regarded as an indolent disease yet treatable with purine analogs. We are going to present a complete long-term clinical and prognostic report of our HCL patients as a large cohort in Iran. Methods: All patients diagnosed with HCL according to WHO criteria referred to our academic center in the period of 1995 to 2020 are enrolled. Treatment with daily cladribine regimen was initiated as indicated and patients were followed. Survival data and clinical outcome of patients were calculated. Results: A total 50 patients were studied (76% male). Median time to treatment was 4.8 months and complete remission was achieved in 92% of patients. Nine patients (18%) experienced relapse with median time to relapse of 47 months. After median follow-up of 51 months, the median OS was not reached and after 234 months, the overall survival rate was 86%. Survival was worse in patients with non-classic HCL (vHCL) compared to classic HCL. Conclusion: Our long-term follow up data confirmed favorable outcome of Iranian HCL patients with cladribine and provide a useful viewpoint of the disease. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1807 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1807/954

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 16 4 2022 10 15 217 223 Mozaffar Aznab Department of Internal Medicine, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran Babak Izadi Molecular Pathology Research Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran Farhad Amirian Molecular Pathology Research Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran Sedigheh Khazaei 1) Molecular Pathology Research Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran 2) Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran Seyed Hamid Madani Molecular Pathology Research Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran Mazaher Ramezani Molecular Pathology Research Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran 2020 08 28 2022 01 09   Background: Amplification of HER2 is an important factor in the diagnosis and treatment of breast cancer. Fluorescence in situ hybridization (FISH) is the gold standard for the detection of HER2-positive tumors. However, the Immunohistochemistry (IHC) assay for the detection of HER2 is more popular in the preclinical laboratory since it is faster and more economical compared to the FISH test. Materials and Methods: In this study, the status of HER2 amplification is determined by the FISH test using 44 formalin-fixed paraffin-embedded tissue samples and comparing the results with the IHC test to determine the reliability of the IHC test. Also, the relationship between HER2 amplification and estrogen, progesterone receptors, P53, age, menopausal status, family history of breast cancer, tumor size, and histological grade were determined. Results: Examination of HER2 in 44 samples by IHC showed 3 (6.8%) and 5 (11.4%) samples were positive (IHC 3+) and negative (IHC 0, 1+), respectively, and 36 (81.8%) samples were ambiguous (IHC 2 +), but examination by FISH showed 21 samples (47, 7%) were positive and 23 samples (52, 3%) were negative. There was a significant difference between IHC and FISH in the detection of HER2 amplification (P=0.019). Also, there was a significant difference between HER2 amplification and menopause in patients (P=0.035). Conclusion: This result demonstrated that the IHC test is not a reliable test to determine HER2 amplification. This study represented that FISH analysis is more reliable than IHC and must be preferentially performed for all cases, especially for HER2 +2 cases for whom the IHC result is 2+. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1422 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1422/949

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 16 4 2022 10 15 224 230 Shahabeddin Hatefi Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Aida Kadkhodaei Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran Babak Nejati Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Saba Ghaffary Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 2021 05 30 2022 09 13 Background: Drug-drug interaction (DDI) occurs when the pharmacological effect of a drug is altered due to concomitant administration with other drugs. DDIs still remain a serious issue; thus, we conducted this retrospective study to evaluate DDIs prevalence in our care center. Methods: All admitted patients with any kind of malignancies that received at least two medications from oncology and non-oncology classifications during six months were enrolled in this study. All relevant data including, patients’ demographic information, diagnosis, hospitalization duration, and all administered medication during hospitalization were recorded. The DDI was assessed by using the latest version of Lexi-interact. Results: Each patient received a mean number of 11.6±4.7 medications. The number of non-oncology drugs demonstrated a remarkable correlation with the number of interactions (P<0.001). Whereas, the number of oncology drugs does not have any relation with the number of interactions (P=0.64). Among the 763 detected DDIs during this study, the incidence of major, moderate and minor interactions were 31.2%, 61.4%, and 7.3%, respectively. Conclusion: Our results highlighted the clinical significance of DDIs, considering that 104 (92%) patients had at least one DDI. The main reason that could have potentially contributed to this outcome is the complicated nature of cancer treatment and clinical management. We believe that using computer software to collect all prescribed and OTC collaboration of clinical pharmacists with oncologists can reduce the potential interactions prior to drug administration. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1645 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1645/950

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 16 45 55 EN Masumeh Sanaei Research Center for Non-communicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran Fraidoon Kavoosi Research Center for Non-communicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran Zahra Esmi Research Committee Student, Jahrom University of Medical Sciences, Jahrom, Iran 2019 04 16 2019 07 31 Background: Aberrant methylation and histone deacetylation of tumor suppressor genes (TSGs) are the most epigenetic alterations involving in tumorigenesis. Overexpression of DNA methyltransferases (DNMTs) and histone deacetylase 1 (HDAC1) have been reported in several cancers. The reversion of hypermethylation and deacetylation by epi-drugs such as 5-aza-2′-deoxycytidine (5-AZA-CdR) and vorinostat (SAHA) can restore normal expression of TSGs. Previously, we reported that 5-AZA-CdR and valproic acid (VPA) can inhibit DNMT1 in hepatocellular carcinoma (HCC). The aim of this study was to investigate the effect of 5-AZA-CdR in combination to and in comparison with SAHA on DNMT1, DNMT3a, DNMT3b, histone deacetylase 1 (HDAC1), glutathione S-transferase 1 (GSTP1) and suppressor of cytokine signaling 1 (SOCS1)  genes expression, cell growth inhibition and apoptotic induction in hepatocellular LCL-PI 11 cell line. Materials and Methods: The cells were treated with 5-AZA-CdR and SAHA and then MTT assay, cell apoptosis assay and Real-time quantitative RT-PCR (qRT-PCR) were done. Results: Both agents indicated significant inhibitory and apoptotic effect (P< 0.001). The apoptotic effect of SAHA was more than that of 5-Aza-CdR. The result of qRT-PCR indicated that 5-Aza-CdR decreased DNMT1, DNMT3a, DNMT3b and increased GSTP1and SOCS1 genes expression and SAHA decreased HDAC1 and increased GSTP1 and SOCS1 genes expression significantly. Maximal apoptosis and genes expression were seen with combined treatment. Conclusion: 5-AZA-CdR and SAHA down-regulated DNMT1, DNMT3a, DNMT3b, and HDAC1 and up-regulated GSTP1 and SOCS1 gene expression by which inhibited cell viability and induced apoptosis, suggesting that they could be used in the treatment of HCC. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1115 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1115/811

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 14 1 2020 01 01 56 71 Amir Abbasnezhad Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran Mehdi Habibi Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran Babak Abdolkarimi Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran Soodabeh Zare Department of Biostatistics, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran Ezatollah Fazeli Moghadam Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran Razieh Choghakhori Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran. AND Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran 2019 05 18 2019 06 02 Background: To investigate the serum levels of 25(OH)D and minerals in adults and children with haemophilia A, and the possible association of these factors with Pediatric Haemophilia/Haemophilia Activities List (PedHAL/HAL), Haemophilia Joint Health Score (HJHS) and Haemophilia-specific quality of life (QoL) index this case-control study was conducted. Materials and Methods: Eighty five haemophilia A patients (HP) registered in Hemophilia Society of Lorestan province were recruited. Along with HP, sex and age matched healthy controls (HCs) were recruited. Linear regression was used to evaluate the possible relation between biochemical factors and other variables. One-way analysis of variance (ANOVA) was used to compare the biochemical factors between three or more independent groups. Results: Results indicated that serum zinc, phosphorus and magnesium were significantly lower, whereas, serum level of alkaline phosphatase (ALP) was statistically higher in HP compared with HCs. Other biochemical factors including calcium and parathyroid hormone (PTH) were not different between groups. Serum 25(OH) D was lower only in children with haemophilia and not in adults. Percentage of subjects who were vitamin D deficient was higher in HP vs. HCs (57.6% vs. 35.3%), and also this rate was higher in children with haemophilia vs. adults (77.8% vs. 48.3%). Lower serum concentrations of assessed minerals and vitamin D were associated with lower physical activity, poor QoL and worst joint health, and these associations were stronger in children. Conclusion: Present study indicated that serum levels of vitamin D and minerals were low in HP, and these low levels were associated with poor QoL, lower physical activity and worst joint health. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1136 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1136/812 <