Publications by authors named "Seyed Asadollah Mousavi"

31 Publications

The impact of ICAM-1, CCL2 and TGM2 gene polymorphisms on differentiation syndrome in acute promyelocytic leukemia.

BMC Cancer 2021 Jan 9;21(1):46. Epub 2021 Jan 9.

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Although arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are well-tolerated and effective treatments for Acute Promyelocytic Leukemia (APL), Differentiation Syndrome (DS) is a lethal side effect in some patients. The pathogenesis of DS is complex and not well understood; however, it is considered as an inflammatory response due to cytokines release of differentiated cells. Moreover, adhesion molecules that are widely expressed on the surface of differentiated cells and gene expression changes of transglutaminase2 (TGM2) are mechanisms involved in the development of DS. The purpose of this study was to assess the association of single nucleotide polymorphisms (SNP) of Intercellular Adhesion Molecule-1 (ICAM-1), chemokine (C-C motif) ligand 2 (CCL2) and TGM2 as inflammatory factors with differentiation syndrome susceptibility.

Methods: DNA was extracted from 133 APL patients and 100 normal controls. Assessment according to the PETHEMA criteria revealed that 13.5% of these patients experienced differentiation syndrome. Tetra-ARMS PCR and PCR-RFLP were done to amplify DNA fragments in APL patients with and without DS. Then DNA sequencing was done to validate the results. SNPStats, SPSS and Finch TV were used to analyze the results.

Results: A significant correlation was found between rs4811528 in the TGM2 gene and differentiation syndrome susceptibility (P = 0.002, 95% CI = 1.74-18.81, OR = 5.72) while rs5498 in ICAM-1, rs1024611 in CCL2, and rs7270785 in TGM2 genes showed no correlation with differentiation syndrome. The G allele of rs7270785 and rs4811528 showed a haplotypic association with differentiation syndrome (P = 0.03, 95% CI = 1.13-13.86, OR = 3.96).

Conclusions: AA genotype of the TGM2 SNP (rs4811528) may be a risk factor for development of DS in patients with APL following the use of ATRA/ATO.
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http://dx.doi.org/10.1186/s12885-021-07783-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797108PMC
January 2021

Treatment protocols for BK virus associated hemorrhagic cystitis after hematopoietic stem cell transplantation.

Am J Blood Res 2020 15;10(5):217-230. Epub 2020 Oct 15.

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences Tehran, Iran.

Hematopoietic stem cell transplantation (HSCT) represents a vital curative choice for many disease. However its outcome can be hampered by a variety of transplant associated complications. Hemorrhagic cystitis (HC) considered as one of the major difficulties after HSCT. HC symptoms comprise hematuria, dysuria, burning during urination, urinary frequency, urgency and incontinency, abdominal or suprapubic pain, urinary obstruction, and renal or bladder damage. There are a lot of causes for HC development. BK virus reactivation is one of the major causes of HC after HSCT. There is still no standard and approved treatment protocol for BK virus associated HC (BKV-HC). Treatment of HC is according to the local standard operating procedures, depending on the cause and severity. In this study we will review the current treatments available for this disease. We have divided the therapeutic procedures into 5 categories including conservative therapy, complimentary options, surgical procedures, pharmacological treatments and adoptive cell therapy. We believe that comparing the advantages and disadvantages of different therapies make it easier to choose the best treatment protocol. In addition, we had a greater focus on adoptive cell therapy, because it is a relatively new introduced method and might be a logical alternative to conventional treatments for refractory patients. In total, no definitive recommendation is possible for current available treatments because these procedures have only been utilized sporadically in a limit number of patients. Furthermore, a number of treatment options are only experimental and definitely need more effort.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675133PMC
October 2020

Co-transplantation of bone marrow-derived mesenchymal stem cells with hematopoietic stem cells does not improve transplantation outcome in class III beta-thalassemia major: A prospective cohort study with long-term follow-up.

Pediatr Transplant 2020 Nov 11:e13905. Epub 2020 Nov 11.

Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Bone marrow transplantation is the only curative treatment for beta-thalassemia major. Data on the co-transplantation of MSCs with HSCs in beta-thalassemia major patients are scarce. We aimed to investigate the outcomes of thalassemia major patients who underwent bone marrow-derived MSC co-transplantation with HSCs compared with those who only received HSCs. This prospective randomized study included patients with class III thalassemia major undergoing HSCT divided randomly into two groups: Thirty-three patients underwent co-transplantation of bone marrow-derived MSCs with HSCs, and 26 patients only received HSCs. Five-year OS, TFS, TRM, graft rejection rate, and GVHD were estimated. The 5-year OS was 66.54% (95% CI, 47.8% to 79.9%) in patients who underwent co-transplantation of MSCs with HSCs vs 76.92% (95% CI, 55.7% to 88.9%) in patients who only received HSCs (P = .54). No significant difference was observed in the 5-year TFS between the two groups (59.1% vs 69.2%; P = .49). The 5-year cumulative incidence of TRM was not statistically significant among patients who underwent co-transplantation of MSCs with HSCs (27.27%) vs those who only received HSCs (19.23%; P = .61). There was no statistically significant difference in graft rejection, acute GvHD, and chronic GvHD between the two groups. Based on our findings, the co-transplantation of MSCs and HSCs to class III thalassemia major patients does not alter their transplantation outcomes including OS, TFS, rejection rate, transplant-related mortality, and GvHD.
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http://dx.doi.org/10.1111/petr.13905DOI Listing
November 2020

Potential of therapeutic plasmapheresis in treatment of COVID-19 patients: Immunopathogenesis and coagulopathy.

Transfus Apher Sci 2020 Dec 2;59(6):102993. Epub 2020 Nov 2.

Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran; Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran. Electronic address:

Therapeutic plasmapheresis (TP) is the process of the separation and removal of plasma from other blood components and is considered as an adjunctive treatment strategy to the discarded abnormal agent in the management of respiratory viral pandemics. This article reviews the mechanisms of immunopathogenesis and coagulopathy induced by SARS-CoV-2 and the potential benefits of TP as adjunctive treatment in critically COVID-19 patients.
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http://dx.doi.org/10.1016/j.transci.2020.102993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605792PMC
December 2020

Synthesis, characterization, and in vitro evaluation of the starch-based α-amylase responsive hydrogels.

J Cell Physiol 2021 May 5;236(5):4066-4075. Epub 2020 Nov 5.

Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Controlled-release drug delivery systems are promising platforms in medicine. Among various types of material in drug delivery, hydrogels are interesting ones. They are water-soluble and tissue compatible polymers with a high capacity to carry and release drugs in a controllable manner. In this study, we introduce the synthesis, characterization, and application of an α-amylase responsive hydrogel in controlled drug delivery. The newly synthesized starch-based hydrogels structurally characterized by means of Fourier-transform infrared spectroscopy and scanning electron microscopy. A proapoptotic drug, doxorubicin, was loaded into the hydrogels and the controlled release of the drug was assessed in the presence of α-amylase and ultimately it was evaluated to controlled-drug release in vitro and subsequently in killing cancer cells. Our results highlight the effectiveness of temporal drug delivery using α-amylase responsive hydrogels in killing cancer cells.
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http://dx.doi.org/10.1002/jcp.30148DOI Listing
May 2021

Enterobius vermicularis Infection of the Lung Associated With the Use of Ibrutinib in a Patient With Chronic Lymphocytic Leukemia.

Am J Ther 2020 Oct 10. Epub 2020 Oct 10.

Department of Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.1097/MJT.0000000000001123DOI Listing
October 2020

Prognostic and Therapeutic Significance of Androgen Receptor in Patients with Gastric Cancer.

Onco Targets Ther 2020 2;13:9821-9837. Epub 2020 Oct 2.

Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: The clinical studies carried out in the last few decades unequivocally introduced activated androgen receptor (AR) as a pathogenic feature of human malignancies which not only endows cancer cells with survival advantage, but also may be exploited for anticancer interventions.

Patients And Methods: In this study, we have investigated the expression profile of and EMT-related genes in fresh gastric cancer (GC), adjacent nontumor and normal gastric tissues, as well as the effect and molecular mechanisms of inhibition in GC cell lines.

Results: Amongst 60 GC patients, 66.7% overexpressed that was remarkably correlated with the overexpression of . overexpression was also remarkably associated with unfavorable outcome (HR=3.478, =0.001); however, multivariate Cox regression analysis indicated that it was not an independent prognostic factor (HR=2.089, =0.056). This study has investigated simultaneous assessment of and EMT-related genes expression and indicated that concurrent overexpression of and is an independent unfavorable factor for GC overall survival after adjustment with other variables (HR=2.382, =0.021). Interestingly, the inhibition of signaling by potent antagonist enzalutamide suppressed cell growth, migration and invasion of GC cells via regulation of apoptosis-, cell cycle-, and EMT-related gene expressions.

Conclusion: Our findings have clinical importance proposing as an important prognostic factor involved in GC progression and metastasis, and submit inhibition as an appealing therapeutic approach for GC patients, either as a single agent or in a combined-modal strategy.
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http://dx.doi.org/10.2147/OTT.S265364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537849PMC
October 2020

Outcome of peripheral blood allogeneic hematopoietic stem cell transplantation as a treatment option in patients with severe aplastic anemia between 40 and 50 years.

Hematol Oncol Stem Cell Ther 2020 Jul 3. Epub 2020 Jul 3.

Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

The frontline treatment for patients younger than 40 years with severe aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-identical sibling donor. However, in patients with severe AA who are older than 40 years, allogeneic HSCT has been found to be associated with increased treatment-related mortality and toxicity, even when matched sibling donors are used. We report our institutional experience with allogeneic HSCT in patients with severe AA between 40 and 50 years. A total of 19 patients with severe AA were included in the study. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. The mean age of patients at the time of transplant was 43.79 years, and 57.9% were male. The mortality rate was 36.8%, attributed to infection (10.5%), relapse (15.8%), and renal failure (5.3%) in all cases. Acute graft-versus-host disease (GVHD) occurred in five patients (26.3%), and chronic GVHD occurred in two patients (10.5%). The 5-year OS was 62% and the 5-year DFS was 52%. We found that the patient's age, platelet level prior to transplantation, and the number of CD3 cells infused for each transplant were independent prognostic factors for OS, and the age and sex of the patient, graft rejection, and platelet level prior to transplantation were significant prognostic factors associated with DFS. We recommend that immunosuppressive therapy be considered as a first-line treatment in patients with severe AA who are older than 40 years. Allogeneic HSCT can be considered a valid alternative option in patients whose suppression therapy fails.
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http://dx.doi.org/10.1016/j.hemonc.2020.06.004DOI Listing
July 2020

Long--Term Free Survival of Two Class III β-Thalassemic Patients after Non-Myeloablative Stem Cell Transplantation.

Int J Hematol Oncol Stem Cell Res 2020 Apr;14(2):118-122

Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

At present, hematopoietic stem cell transplantation is the only curative treatment for β thalassemia patients. Conventional myeloablative stem cell transplantation is associated with significant morbidity and mortality, and non-myeloablative stem cell transplantation is associated with high graft failure rate. Some modification in this treatment approach can result in successful transplantation in thalassemia patients. Two successful Fludarabine-based non-myeloablative stem cell transplantation in two Class III β thalassemia patients are reported here. The first patient was a 14-year old girl that developed rapid engraftment and full chimerism after rapid tapering of cyclosporine as graft-versus-host disease (GVHD) prophylaxis drug according to our protocol. Another patient was a 24-year old female patient that developed cyclosporine toxicity, and early tapering of cyclosporine helped for rapid engraftment and successful transplantation. After these two successful experiments in non-myeloablative peripheral blood stem cell transplantation for our class III β thalassemia patients, we concluded that Fludarabine-based non-myeloablative stem cell transplantation with adequate number of stem cells at the time of transplantation and rapid tapering of GVHD prophylaxis drugs after transplantation can potentially help for rapid engraftment and successful stem cell transplantation in high risk β-thalassemia patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231797PMC
April 2020

Methylation Analysis of and in Circulating Cell-Free DNA for Detection of Gastric Cancer: A Validation Study.

Avicenna J Med Biotechnol 2020 Apr-Jun;12(2):99-106

Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: Most of Gastric Cancer (GC) patients are diagnosed at an advanced stage with poor prognosis. Hypermethylations of several tumor suppressor genes in cell-free DNA of GC patients have been previously reported. In this study, an attempt was made to investigate the methylation status of and and their potentials for early diagnosis of GC.

Methods: Methylation status of the four tumor suppressor genes in 96 plasma samples from histopathologically confirmed gastric adenocarcinoma patients (Stage I-IV) and 88 healthy controls was determined using methylation-specific PCR method. Receiver operating characteristic curve analysis was performed and Area Under the Curve (AUC) was calculated. Two tailed p<0.05 were considered statistically significant.

Results: Methylated , and were significantly higher in the GC patients (41.7, 33.3, 66.7, and 58.3%) compared to the controls (15.9, 0.0, 6.8, and 4.5%), respectively (p<0.001). Stratification of patients showed that (AUC: 0.70, Sensitivity: 0.47, Specificity: 0.93, and p<0.001) and (AUC: 0.77, Sensitivity: 0.59, Specificity: 0.95, and p<0.001) had the highest performances in detection of early-stage (I+II) GC. The combined methylation of and in detection of early-stage GC had a higher AUC of 0.88 (SE=0.042; 95% CI:0.793-0.957; p<0.001), higher sensitivity of 0.82 and reduced specificity of 0.89.

Conclusion: Methylation analysis of and in circulating cell free-DNA of plasma could be suggested as a potential biomarker for detection of GC in early-stages.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229449PMC
May 2020

Differential microRNAs expression in acute graft-versus-host disease as potential diagnostic biomarkers.

Bone Marrow Transplant 2020 12 13;55(12):2339-2342. Epub 2020 May 13.

Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

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http://dx.doi.org/10.1038/s41409-020-0949-7DOI Listing
December 2020

A Single Center Study of Prescribing and Treatment Outcomes of Patients with Chronic Myeloid Leukemia.

Int J Hematol Oncol Stem Cell Res 2020 Jan;14(1):11-18

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The present study investigated the patients with Chronic Myeloid Leukemia in chronic phase (CP-CML) who had been on the first- line Imatinib Mesylate (IM) therapy for a period of 84 months. : This retrospective study was conducted in 295 newly-diagnosed CP-CML patients(age >18 years) who were admitted to the Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran during 1 January, 2009 to 30 December, 2016. Response to treatment was evaluated by molecular response assessment. Rates of IM dose adjustment, switching to another drug therapy, progression to Accelerate Phase (AP) and Blastic Crisis (BC) and long-term outcomes included Overall Survival (OS) and Progression Free Survival (PFS) were assesed. Patients' average age was 41.7 years, and 52.9% were male. 44.4% of patients at the month 18 achieved Major Molecular Response (MMR). Progression to AP/BC occurred in 26 patients during 84 months, and the estimated rate of OS and PFS were 71.83 and 74.48, respectively. Among the patients who did not achieve MMR at month 18 , 61 patients were treated with IM ( 400 mg /day), and then after month 18, 24(39.3%) of whom achieved MMR. Dose adjustments occurred in 60 patients (20.33%). IM dose increase was observed in 53 patients who did not achive optimal response to imatinib or loss of optimal response. IM dose decrease was observed in 7 patients. 25 (8.47%) patients were switched to a different Tyrosine Kinase Inhibitor (TKI). Most of TKI changes(n=21) happened in patients who did not achieve optimal response to IM and TKI changes owing to adverse events of IM were observed in 4 patients.. Among the patients undergoing change in treatment, 24(43.75%) patients achieved MMR. Our data showed the high effectiveness of the change in the treatment of IM-resistant condition. Moreover, our finding suggests that imatinib be effective in Iranian patients after a long period of time compared to the referenced studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167602PMC
January 2020

Investigation of the Correlation between Androgen Receptor and ZEB1 and its Value in Progression of Gastric Cancer.

Avicenna J Med Biotechnol 2020 Jan-Mar;12(1):52-60

Hematology, Oncology and Stem Cell Transplantation Research Institute, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: Zinc-finger Enhancer Binding protein (ZEB1) acts as a transcription factor to promote cancer progression through regulating Epithelial to Mesenchymal Transition (EMT). It is well-known that ZEB1 mRNA expression is directly induced by both Estrogen Receptor (ER) and Progesterone Receptor (PR). Moreover, Androgen Receptor (AR) and PR could bind to the same regulatory element. Since it has been shown that AR overexpresses in Gastric Cancer (GC) as a male-predominant tumor, the goal of this study was to evaluate whether AR could regulate ZEB1 expression in GC.

Methods: The expression profile of ZEB1 in 60 fresh GC and adjacent non-tumor tissues and 50 normal gastric specimens was assessed by qRT-PCR, and the association of ZEB1 expression with clinicopathological features was investigated. Furthermore, possible correlation between ZEB1 and AR was evaluated to elucidate a novel prognostic marker using Kaplan-Meier method and Cox regression model. Finally, molecular interaction of ZEB1 and AR was assessed using a potent AR antagonist in GC cells.

Results: Among GC patients, 70.2% (40/57) overexpressed ZEB1 and 64.91% (37/57) overexpressed AR relative to normal gastric tissues. ZEB1 overexpression was significantly correlated with the AR overexpression in GC patients. Moreover, ZEB1 overexpression was remarkably associated with lower overall survival; however, it was not an independent prognostic factor. Evidence shows that simultaneous evaluation of ZEB1 and AR expression could independently predict survival of GC patients (HR= 2.193, p=0.047).

Conclusion: These findings have clinical importance suggesting simultaneous evaluation of ZEB1 and AR expression as a potential prognostic marker. Moreover, AR may regulate ZEB1 expression in GC cells proposing a possible promising targeted therapy for GC patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035462PMC
March 2020

Evaluation of the Association between Androgen Receptor and AURKA and Its Prognostic Value in Gastric Cancer.

Int J Hematol Oncol Stem Cell Res 2019 Oct;13(4):174-182

Hematology, Oncology and Stem Cell Transplantation Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

It is well-known that Aurora kinase A (AURKA) shows oncogenic properties in various tumor types including gastric cancer (GC). Moreover, previous studies have demonstrated that AURKA has a specific androgen receptor (AR) binding site in its promoter; thus, it could be regulated by AR. Since it has been shown that AR overexpresses in gastric cancer (GC) as a male-predominant tumor, the goal of this study was to evaluate the association between AR and AURKA and its prognostic value in GC patients. : We assessed the expression profile of AURKA in 60 fresh GC and adjacent non-tumor tissues and 50 normal gastric specimen by qRT-PCR, and investigated the association of AURKA expression with clinicopathological features. Furthermore, we evaluated possible correlation between AURKA and AR to elucidate a novel prognostic marker using Kaplan-Meier method and Cox regression model. Among GC patients, 65% (39/60) overexpressed AURKA relative to normal gastric tissues. AURKA overexpression was significantly correlated with the AR overexpression in GC patients. Although AURKA expression alone was not remarkably associated with poor outcome, we provided some evidence that combined evaluation of AURKA and AR expression could independently predict survival of GC patients adjusted for other variables (HR=1.7, CI=1.314-3.833 p=0.042). These results indicate that AR and AURKA may crosstalk to promote GC progression. Our findings have clinical importance because they suggest simultaneous assessment of AURKA and AR expression as a novel potential prognostic marker.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925368PMC
October 2019

Effects of mobilized peripheral blood stem cells on treatment of primary lower extremity lymphedema.

J Vasc Surg Venous Lymphat Disord 2020 05 16;8(3):445-451. Epub 2019 Dec 16.

Pathology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Objective: Lymphedema is a chronic debilitating disease characterized by the accumulation of fluid in the extremities as a result of lymphatic system impairment. Current treatments fail to restore the functionality and structural integrity of the lymphatic vessels lost in this condition. In this study, autologous mobilized peripheral blood stem cell transplantation was used and its potential efficacy and safety were evaluated in treating this condition.

Methods: Ten patients with primary lymphedema in the lower extremity received granulocyte-colony stimulating factor subcutaneously for 4 days, to stimulate stem cell mobilization, after which 200 to 250 mL of blood was drawn from each patient and used to collect stem cells. Mobilized stem cells were counted by flow cytometry with International Society of Hematotherapy and Graft Engineering method. In two sessions, 3 weeks apart, these stem cells were injected subcutaneously in the affected limb at approximately 80 points, along the lymphatic vessels. Each patient was followed for 6 months, during which changes in the limb volume and circumference were measured. Lymphangiogenesis was evaluated by biopsy, the lymphoscintigraphic transport index was calculated using Lymphoscintigraphy, and quality of life was surveyed.

Results: In this study, patients received on average 9.5 ± 6.8 × 10 mononuclear cells (which divided into 2 × 10 CD34 cells for each session) in two sessions. The volume of the lower limbs decreased in 60% of patients. One patient showed a slight increase in the volume of lower limbs and three showed no change. The average limb volume was 4469.41 ± 1760.71 cm, which on average differed from the average initial limb volume by 232.88 ± 392.53 cm. Quality of life was reported as slightly increased in 60% of patients. The lymphoscintigraphic transport index suggested improvement in 60% of the patients. Likewise, tissue samples showed a 60% increase in lymphatic vessels.

Conclusions: Subcutaneous injection of autologous hematopoietic stem cells harvested from peripheral blood into patients with primary lower limb lymphedema is feasible, potentially effective, and without serious adverse effects. However, a larger scale study with more patients is needed to validate our results. Last, to increase the effectiveness of this treatment, the optimal dose of cells injected and the requirement for additional growth factors need further study.
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http://dx.doi.org/10.1016/j.jvsv.2019.10.019DOI Listing
May 2020

Microvesicles of osteoblasts modulate bone marrow mesenchymal stem cell-induced apoptosis to curcumin in myeloid leukemia cells.

J Cell Physiol 2019 08 27;234(10):18707-18719. Epub 2019 Mar 27.

Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Microvesicles (MVs) derived from bone marrow niche components have an important role in genetic reprogramming and subsequent drugs induce apoptosis in leukemic cells. Here, we have found that undertreatment of curcumin or daunorubicin, the cross-talk through MVs of KG-1-bone marrow mesenchymal stem cells (BMSCs), significantly downregulates the expression of the survival gene osteopontin (OPN), CXCL-12, IL-6 (interleukin-6), STAT-3, and VCAM-1 (vascular cell adhesion molecule 1) in treated-KG-1 cells as well as exclusively upregulates CXCL-12 in BMSCs. Drug treated-cell populations' MVs of both single cultured osteoblasts (OBs) and cocultured KG-1 + BMSCs + OBs similarly upregulate survival mediators' OPN, CXCL-12, IL-6, STAT-3, and VCAM-1 in treated-KG-1 cells. Likewise, isolated MVs from KG-1 cells or communication between KG-1, BMSCs, and OBs treated by drugs increase the expression of genes OPN, CXCL-12, IL-6, STAT3, and VCAM-1 by OBs. MVs derived from KG-1 + BMSCs + OBs reduce drug-induced apoptosis in KG-1 cells. This suggests MVs-mediated information transfer is a procedure whereby OBs could overcome BMSCs-induced apoptosis in drug-treated-KG-1 cells.
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http://dx.doi.org/10.1002/jcp.28511DOI Listing
August 2019

Autologous Platelet-Released Growth Factor and Sexual Dysfunction Amendment: A Pilot Clinical Trial of Successful Improvement Sexual Dysfunction after Pelvic Irradiation

Asian Pac J Cancer Prev 2019 03 26;20(3):817-823. Epub 2019 Mar 26.

Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Sexual dysfunction (SDF) is a common sequel to cancer treatment which affects the quality of life in women treated with pelvic radiotherapy. The aim of this study was to evaluate the safety, symptom resolution and objective improvement the injection of autologous platelet released growth factor (APRGF) for treatment of SDF in cited patients. This prospective pilot study enrolled 10 cancer-free patients with SDF who underwent pelvic radiotherapy at least 5 years ago, randomly. Each patient was received 1-2 cc APRGF within four weeks and all patients were re-evaluated at eight weeks and six months. CD34 immuno histochemistry and Masson’s trichrome staining were performed on vaginal biopsy section for angiogenesis and fibrosis assay respectively. Sexual satisfaction after the injection of APRFG was clinically difference and the entire patient had sexual satisfaction. In the patient’s follow-up, none of them needs to repeat the treatment. Our results declared that APRGF injection was effective and symptoms were disappeared in the entire patients. Significant objective improvements in vaginal diameter (mean before injection, 6.5 cm vs 7.1 cm after injection) (p-value = 0.001) and vaginal flexibility (mean before treatment, 0.72 cm vs 1.85 cm after injection) (P-value = 0.026) were observed. Characteristics of discharge before the injection in 60% of patients were included dry vagina and 40% had mild discharge but after injection 40% of patients had moderate and also 60% had mild and sufficient discharge (P-value= 0.190). Overally, our patients reported better sexual function and showed better vaginal function indexes, after APRFG injection.
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http://dx.doi.org/10.31557/APJCP.2019.20.3.817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825769PMC
March 2019

Prognostic Value of RUNX1 Mutations in AML: A Meta-Analysis

Asian Pac J Cancer Prev 2018 Feb 26;19(2):325-329. Epub 2018 Feb 26.

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The RUNX1 (AML1) gene is a relatively infrequent mutational target in cases of acute myeloid leukemia (AML). Previous work indicated that RUNX1 mutations can have pathological and prognostic implications. To evaluate prognostic value, we conducted a meta-analysis of 4 previous published works with data for survival according to RUNX1 mutation status. Pooled hazard ratios for overall survival and disease-free survival were 1.55 (95% confidence interval (CI) = 1.11–2.15; p-value = 0.01) and 1.76 (95% CI = 1.24–2.52; p-value = 0.002), respectively, for cases positive for RUNX1 mutations. This evidence supports clinical implications of RUNX1 mutations in the development and progression of AML cases and points to the possibility of a distinct category within the newer WHO classification. Though it must be kept in mind that the present work was based on data extracted from observational studies, the findings suggest that the RUNX1 status can contribute to risk-stratification and decision-making in management of AML.
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http://dx.doi.org/10.22034/APJCP.2018.19.2.325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980915PMC
February 2018

Comparison of induction therapy in non-high risk acute promyelocytic leukemia with arsenic trioxide or in combination with ATRA.

Leuk Res 2018 03 3;66:85-88. Epub 2018 Feb 3.

Hematology-Oncology and Stem Cell Transplantation Research Center/Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Acute promyelocytic leukemia (APL) is a curable form of acute myeloid leukemia; in recent years, the use of new treatment strategies, such as combination therapy, have led to improved APL outcomes. Here, outcomes of patients treated with a combination of arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) are compared against patients treated with single ATO therapy.

Patients And Methods: In total, 67 patients with non-high-risk APL were evaluated. A group of 30 patients received ATO, and another group of 37 patients received ATO plus ATRA. ATO infusion at a dose of 0.15 mg/kg/day was continued till complete remission was achieved or till 60 days of consumption, and after 28 days of rest, second ATO course was initiated for 28 days as consolidation. Four courses separated by 28-day rest were planned. In the second group, 45 mg/m/day ATRA was added to ATO protocol.

Results: All patients except one in the ATO group and all patients in the ATO plus ATRA group were alive after a median follow-up of 18 and 17 months, respectively; 2.5-year overall survival in the ATO group was 86% (p-value = .32). Five patients in the ATO group experienced relapse, and 2.5-year leukemia-free survival in this group was 60%. No relapse occurred in the ATO plus ATRA group (p-value = .01). Differences in the mean of white blood cell (p-value = .67), platelet (p-value = .15), liver (p-value = .37), and renal (p-value = .95) dysfunctions were not significant.

Conclusion: Although ATO has been considered a first-line therapy in patients with APL, several studies have reported improved outcomes with a combination of ATO plus ATRA. This study demonstrated a significant decrease in relapse with this combination compared with single ATO therapy and supported the importance of ATRA in APL treatment.
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http://dx.doi.org/10.1016/j.leukres.2018.01.019DOI Listing
March 2018

The Relationship between STR-PCR Chimerism Analysis and Chronic GvHD Following Hematopoietic Stem Cell Transplantation.

Int J Hematol Oncol Stem Cell Res 2017 Jan;11(1):24-29

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The study attempts to assess the relationship between chimerism analysis using polymerase chain reaction of short tandem repeat (STR) and the incidence of chronic graft versus host disease (GvHD) as well as survival. The retrospective cohort included all patients who received allo-HSCT during 2005-2013. Data collected by day +100 were reviewed in terms of the incidence of chronic GvHD and survival. Chimerism was evaluated for whole blood, T-cell and PMN cells on days 15, 30 and 60, respectively using polymerase chain reaction of short tandem repeat (STR). Forty (69%) patients developed chronic GvHD, 11 (19%) relapsed and 22 (39.7%) expired during the study. There was a significant relationship between chronic GvHD and chimerism analysis including whole blood on day 60 (p=0.001), Polymorphonuclear neutrophil (PMN) on day 60 (p=0.05), T-cell on days 15 (p=0.028), 30 (p=0.01) and 60 (p=0.004). Patients with chronic GvHD showed a long-term survival as compared with those without chronic GvHD (p=0.0013). Conducting continuous analysis of chimerism provides an opportunity to initiate immediate measures in order to prevent complications.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338278PMC
January 2017

Conjugated Estrogen in Late-Onset Hemorrhagic Cystitis Associated with Hematopoietic Stem Cell Transplantation.

Int J Hematol Oncol Stem Cell Res 2017 Jan;11(1):13-18

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Hemorrhagic cystitis (HC) is one of the most challenging complications in hematopoietic stem cell transplantation (HSCT). Estrogen is one of the suggested treatments for controlling this problem. We performed a randomized case-control study to evaluate the efficacy of oral conjugated estrogen on HC management in 56 HSCT patients. Patients were randomly assigned to the drug group (received 6.25 mg conjugated estrogen oral tablets in a daily single dose during hematuria period) or control group. The median time to complete response was 36 and 24 days in the drug and control group, respectively. The median time of down stage was 24 days in the drug group and 12 days in control group. Adjusted for HC grades, the relative risk of complete response for patients in control group was 1.613 times more than that of patients in drug group; nevertheless, not significant (p=0.122). Our study did not show any benefit in use of oral conjugated estrogen in the management of HC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338276PMC
January 2017

Allogeneic hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria: a retrospective single-center study.

Hematol Oncol 2017 Dec 20;35(4):935-938. Epub 2016 Oct 20.

Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease of hematopoietic stem cell characterized by complement mediated intravascular hemolysis. There are different treatment modalities available for PNH, such as supportive care, eculizumab, and hematopoietic stem cell transplantation (HSCT); only the last one has a potential curative role. This study reported the outcome of HSCT transplanted PNH patients. Thirteen PNH patients between 2002 and 2014 participated in this study. All had full-matched sibling donors, and the conditioning regimen was Bu/Cy (busulfan plus cyclophosphamide), and the source of stem cells was peripheral blood of the donors. Mean age at transplant was 27.46 years, and mean time to transplant was 41.30 months. Three were female and 10 were male. Three patients died at the end of follow-up time, and the cause of death was graft versus host disease (GVHD) for all 3 cases. Survival analysis showed a 5-year and a 13-year survival rate of 74.07% and a significant relationship between a positive history of thrombosis and a higher mortality rate. HSCT has curative role in management of PNH with an acceptable survival rate and therefore can be considered as an acceptable choice for selected cases.
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http://dx.doi.org/10.1002/hon.2367DOI Listing
December 2017

Non-TBI hematopoietic stem cell transplantation in pediatric AML patients: a single-center experience.

J Pediatr Hematol Oncol 2013 Aug;35(6):e239-45

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Hematopoietic stem cell transplantation (HSCT) has been established as a promising treatment in acute myeloid leukaemia (AML). Several studies have been performed to minimize the toxicity of HSCT in children without impairing the efficacy. We report our long-term results of HSCT in pediatric AML patients using non-total body irradiation conditioning regimen.

Procedure: From May 1991 to June 2010, 133 pediatric patients with AML (age<15 y) who were referred to our institute underwent autologous (auto-) or allogeneic (allo-) HSCT. The conditioning regimen consisted of oral busulfan plus etoposide in auto-HSCT patients and oral busulfan plus cyclophosphamide in allo-HSCT patients.

Results: Overall survival (OS), leukemia-free survival (LFS), probability of relapse, and transplantation-related mortality at 3 years were 67.6%, 62.2.5%, 27.3%, and 10.1%, respectively. There was no significant difference between allo-HSCT and auto-HSCT groups. In multivariable analysis using Cox proportional hazards regression model, male sex was associated with significantly improved OS (P<0.001) and LFS (P=0.022). An age ≤3 years was associated with higher relapse (P=0.034) and worse OS (P=0.001) and LFS (P=0.014).

Conclusions: The role of allo-HSCT in pediatric AML patients in first complete remission is uncertain. Further randomized studies are recommended to clarify the optimal postremission therapy in these patients.
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http://dx.doi.org/10.1097/MPH.0b013e31827080fcDOI Listing
August 2013

The outcome of allogeneic hematopoietic stem cell transplants without total body irradiation in pediatric patients with acute lymphoblastic leukemia: single centre experience.

J Pediatr Hematol Oncol 2012 Mar;34(2):101-7

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The most widely accepted conditioning regimen to allogeneic hematopoietic stem cell transplantation consists of total body irradiation, especially in patients affected by acute lymphoblastic leukemia (ALL). In this retrospective study, we report our experience on hematopoietic stem cell transplantation in 44 pediatric patients with acute lymphoblastic leukemia using a non-radiation-based conditioning regimen (busulfan/cyclophosphamide). Median age at transplantation was 12.5 years (range, 4 to 14 y). 39 out of 44 patients received transplants in complete remission. At a median follow-up of 390 days, the probabilities of 3-year disease-free survival and overall survival were 50% and 68%, respectively. Disease status of hematopoietic stem cell transplantation was the only significant variable affecting the overall survival. Acute and chronic graft-versus-host disease occurred in 23 (64%) and 12(18%) patients, respectively. Relapse was significantly higher among patients transplanted in advanced disease status. The results of the study indicate that non-radiation-based preparative regimens can be used in pediatric patients with ALL. However, well-designed comparative trials are needed to better clarify the difference between radiation and non-radiation-based conditioning regimens in pediatric ALL.
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http://dx.doi.org/10.1097/MPH.0b013e31824435a1DOI Listing
March 2012

Hematopoietic stem cell transplantation in the Eastern Mediterranean Region (EMRO) 2008-2009: report on behalf of the Eastern Mediterranean Bone Marrow Transplantation (EMBMT) Group.

Hematol Oncol Stem Cell Ther 2011 ;4(2):81-93

King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Background: The Eastern Mediterranean Bone Marrow Transplantation (EMBMT) Group has accumulated over 25 years of data and experience in hematopoietic stem cell transplantation (HSCT), most particularly in hemoglobinopathies, severe aplastic anemia (SAA), and inherited metabolic and immune disorders, in addition to hematologic malignancies peculiar to the region and where recent updates in trends in activities are warranted.

Objectives: To study trends in HSCT activities in the World Health Organization-Eastern Mediterranean (EM) region surveyed by EMBMT between 2008 and 2009.

Study Design: Retrospective analysis of the survey data, mainly of the cumulative number of transplants, types of transplants (autologous vs. allogeneic), types of conditioning as myeloablative (MAC) vs. reduced intensity conditioning (RIC) and trends in leukemias, hemoglobinopathies, SAA, inherited bone marrow failure syndromes amongst others.

Results And Discussion: Fourteen teams from ten Eastern Mediterranean Region Organization (EMRO) countries reported their data (100% return rate) to the EMBMT for the years 2008-2009 with a total of 2608 first HSCT (1286 in 2008; 1322 in 2009). Allogeneic HSCT represented the majority (63%) in both years. The main indications for allogeneic HSCT were acute leukemias (732; 44%), bone marrow failure syndromes (331, 20%), hemoglobinopathies (255; 15%) and immune deficiencies (90; 5%). There was a progressive increase in the proportions of chronic myeloid leukemia (CML) cases transplanted beyond the first chronic phase (3; 7% of all CML cases in 2008 vs 13; 29% in 2009). The main indications for autologous transplants were plasma cell disorders (345; 36%) Hodgkin disease (256; 27%), non-Hodgkin lymphoma (207; 22%) and solid tumors (83; 9%). RIC continued to show a progressive increase over the years (7% in 2007, 11% in 2008 and 13% in 2009), yet remained relatively low compared to contemporary practices in Europe published by EBMT. The vast majority (95%) of allo-HSCT sources were from sibling donors with a continued dominance of peripheral blood (PB) (1076; 63%), while cord blood transplant (CBT) increased to 83 (5% of allo-HSCT), matched unrelated donor (MUD) remained underutilized (1; 0%) and there were no haploidentical transplants reported. Large centers with >50 HSCT/year showed a plateau of the total number of allo-HSCT over the last 5 years that may be related to capacity issues and needs further study.

Conclusions And Recommendations: There is an overall increased rate of HSCT in the EMRO region with a significant increase in utilization of CBT and allogeneic PB-HSCT as a valuable source. However, further research on outcome data and development of regional donor banks (CB and MUD) may help facilitate future planning to satisfy the regional needs and increase collaboration within the group and globally.
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http://dx.doi.org/10.5144/1658-3876.2011.81DOI Listing
December 2011

Phase II study of single-agent arsenic trioxide for the front-line therapy of acute promyelocytic leukemia.

J Clin Oncol 2011 Jul 6;29(20):2753-7. Epub 2011 Jun 6.

Hematology, Oncology, and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Kargar Ave, Tehran, Iran.

Purpose: The long-term follow-up results of patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid and chemotherapy show high cure rates. Several studies have shown high efficacy of single-agent arsenic trioxide in newly diagnosed APL. However, long-term follow-up results are needed.

Patients And Methods: One hundred ninety-seven patients with newly diagnosed APL were treated with arsenic trioxide 0.15 mg/kg daily intravenous infusion until complete remission (CR). After achieving CR, the patients received one to four more courses of therapy with arsenic trioxide as consolidation and were observed with reverse-transcriptase polymerase chain reaction studies from peripheral blood (to detect of minimal residual disease) every 3 months or until relapse or death.

Results: The morphologic CR rate was 85.8%. The most common cause of remission failure was early death owing to APL differentiation syndrome (13.2%). The most important prognostic factor for early mortality was a high WBC count at presentation. The 5-year disease-free survival (DFS) rate was 66.7% ± 4% (SE). Relapse after 5 years in CR was rare. The 5-year overall survival (OS) rate by intention-to-treat analysis was 64.4% ± 4%. In patients who achieved CR, OS and DFS were identical.

Conclusion: The long-term follow-up of newly diagnosed patients with APL treated with single-agent arsenic trioxide shows high rates of DFS and OS.
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http://dx.doi.org/10.1200/JCO.2010.32.2107DOI Listing
July 2011

99mTc-MIBI whole body scintigraphy and P-glycoprotein for the prediction of multiple drug resistance in multiple myeloma patients.

Hell J Nucl Med 2009 Sep-Dec;12(3):255-9

Research Institute for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Multi-drug resistance (MDR) is a major challenge in the treatment of multiple myeloma (MM). There is low sensitivity of technetium-99m methoxy isobutyl isonitrile ((99m)Tc-MIBI) whole body scan (WBS) in the detection of active MM lesions, because (99m)Tc-MIBI is washed out from malignant cells in the presence of P-glycoprotein (PGP). The objective of the present cohort study was to evaluate of (99m)Tc-MIBI WBS in the prediction of MDR in MM patients during a course of one year follow up. Thirty four patients with MM (25 male, 9 female of mean age 54.12+/-11.46 years) entered the study. Thirteen patients had no previous history of treatment and 21 had a history of previous chemo-radiotherapy. The diagnosis and staging of the disease were based upon routine laboratory and clinical criteria like bone marrow plasma cell count, serum M component, calcium, albumin, beta(2)-microglobulin. Measurements of PGP and WBS using (99m)Tc-MIBI were performed before initialization of treatment and the response to treatment was assessed one year later. The baseline (99m)Tc-MIBI WBS were considered positive for the detection of active lesions when at least one area of non-physiologic increased activity was noted. The follow up (99m)Tc-MIBI WBS was positive for MDR when the patient had active disease but normal WBS. Our results showed that for WBS, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy in active state for the diagnosis of MDR were 38.9%, 62.5%, 70%, 31.2% and 46.1%, respectively. Also the above values for the detection of MDR, using PGP values were 50%, 50%, 69.2%, 30.8% and 50%, respectively. The relative risk of resistant to multiple regimens of chemotherapy after one year follow up in patients with negative to patients with positive (99m)Tc-MIBI WBS was 1.02 (0.60-1.72). In conclusion, we found a low sensitivity of WBS and of PGP in the detection of MDR in patients with active MM. However, both WBS and PGP have 70% and 69% positive predictive value for MDR.
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April 2010

Stem cell transplantation; Iranian experience.

Arch Iran Med 2009 Jan;12(1):69-72

Hematology-Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

From March 1991 through 31st December 2007, 2042 patients underwent stem cell transplantation at the Hematology-Oncology and Stem Cell Transplantation Research Center, affiliated to Tehran University of Medical Sciences. These transplantations included 1405 allogeneic stem cell transplantation, 624 autologous stem cell transplantation, and 13 syngeneic stem cell transplantation. Stem cell transplantation was performed for various diseases including acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphoblastic leukemia, thalassemia major, sickle cell thalassemia, sickle cell disease, multiple myeloma, myelodysplasia, mucopolysaccharidosis, paroxysmal nocturnal hemoglobinuria, non-Hodgkin's lymphoma, Hodgkin's disease, severe aplastic anemia, plasma cell leukemia, Niemann-Pick disease, Fanconi anemia, severe combine immunodeficiency, congenital neutropenia, leukocyte adhesion deficiencies, Chediak-Higashi syndrome, osteopetrosis, histiocytosis X, Hurler syndrome, amyloidosis, systemic sclerosis, breast cancer, Ewing's sarcoma, testicular cancer, germ cell tumors, neuroblastoma, medulloblastoma, renal cell carcinoma, nasopharyngeal carcinoma, ovarian cancer, Wilms' tumor, rhabdomyosarcoma, pancreatoblastoma, and multiple sclerosis. We had 105 cellular therapies for postmyocardial infarction, multiple sclerosis, cirrhosis, head of femur necrosis, and renal cell carcinoma. About 30 patients were retransplanted in this center. About 74.9% of the patients (1530 of 2042) remained alive between one to 168 months after stem cell transplantation. Nearly 25.1% (512 of 2042) of our patients died after stem cell transplantation. The causes of deaths were relapse, infections, hemorrhagic cystitis, graft versus host disease, and others.
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January 2009

Frequency of BCR-ABL fusion transcripts in Iranian patients with chronic myeloid leukemia.

Arch Iran Med 2008 May;11(3):247-51

Hematology-Oncology and Bone Marrow Transplant Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: A specific chromosomal abnormality, the Philadelphia chromosome, is present in 90 - 95% of patients with chronic myeloid leukemia. The aberration results from a reciprocal translocation of chromosomes 9 and 22, creating a BCR-ABL fusion gene. There are two major forms of the BCR-ABL fusion gene, involving ABL exon 2, but including different exons of BCR gene. The transcript b2a2 or b3a2 codes for a p210 protein. Other fusion gene leads to the expression of an e1a2 transcript, which codes for a p190 protein. Other less common fusion genes are b3a3 or b2a3 (p203) and e19a2 (p230). The incidence of one or other rearrangement in chronic myeloid leukemia patients varies in different reports. In general, fusion transcripts are determined individually, a process which is labor- intensive in order to detect all major fusion transcripts. The objective of this study was to set up a multiplex RT-PCR assay for detection and to determine the frequency of different fusion genes in 75 Iranian patients with chronic myeloid leukemia.

Methods: Peripheral blood samples were analyzed by multiplex RT-PCR from 75 adult Iranian chronic myeloid leukemia patients to detect different types of BCR-ABL transcripts of the t(9;22).

Results: All patients examined were positive for some type of BCR/ABL rearrangement. The majority of the patients (83%) expressed one of the p210BCR-ABL transcripts (b3a2, 62% and b2a2, 20%), while the remaining showed one of the transcripts of b3a3, b2a3, e1a2 or co-expression of b3a2 and b2a2. The rate of co-expression of the b3a2 and b2a2 was 5%.

Conclusion: In contrast to other reports, we did not see any co-expression of p210/p190. Co-expression may be due to alternative splicing or to phenotypic variation, with clinical course different from classic chronic myeloid leukemia.
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http://dx.doi.org/08113/AIM.003DOI Listing
May 2008