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Mahnaz Mohammadi Kian, 1, 2 Mahdieh Salemi, 1, 2 Mohammad Bahadoran, 3 Atousa Haghi, 1, 4 Nasrin Dashti, 5 Saeed Mohammadi, 1, 2 Shahrbano Rostami, 1, 2 Bahram Chahardouli, 1, 2 Davood Babakhani, 1 Mohsen Nikbakht 1, 2 1Hematology Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran; 2Hematologic Malignancies Research Center, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; 4Young Researchers & Elite Club Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 5Department of Medical Laboratory Sciences, School of Allied Health Sciences, Tehran University of Medical Sciences, Tehran, IranCorrespondence: Mohsen NikbakhtHematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, IranTel +982184902639Fax +982188004140Email m-nikbakht@sina.tums.ac.irNasrin DashtiDepartment of Medical Laboratory Sciences, School of Allied Health Sciences, Tehran University of Medical Sciences, Tehran, IranTel +989123583690Email dashti@tums.ac.irIntroduction: Acute myeloid leukemia (AML) is a type of blood disorder that exhibits uncontrolled growth and reduced ability to undergo apoptosis. Signal transducer and activator of transcription 3 (STAT3) is a family member of transcription factors which promotes carcinogenesis in most human cancers. This effect on AML is accomplished through deregulation of several critical genes, such as B cell lymphoma-extra-large (BCL-XL) which is anti-apoptotic protein. The aim of this study was to evaluate the effect of curcumin (CUR) and thalidomide (THAL) on apoptosis induction and also the alteration of the mRNA expression level of STAT3 and BCL-XL mRNA on AML cell line compounds.Methods: The growth inhibitory effects of CUR and THAL and their combination were measured by MTT assay in U937 and KG-1 cell lines. The rates of apoptosis induction and cell cycle analysis were measured by concurrent staining with Annexin V and PI. The mRNA expression level of STAT3 and BCL-XL was evaluated by Real-Time PCR.Results: CUR inhibited proliferation and induced apoptosis in both KG-1 and U937 cells and this effect increased by combination with THAL. The expression level of STAT3 and BCL-XL was significantly down-regulated in KG-1 cells after treatment by CUR and THAL and their combination.Conclusion: Overall, our findings suggested that down-regulation of STAT3 and BCL-XL mRNA expression in response to CUR and THAL treatment lead to inhibition of cell growth and induction of apoptosis.Keywords: acute myeloid leukemia, curcumin, thalidomide, STAT3, Bcl-xL

Background : Thrombotic thrombocytopenic purpura (TTP) is associated with microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis. No comprehensive report exists on clinical characteristics and risk factors of relapse and mortality in Iranian TTP patients. In this study, we aimed to report clinical features of Iranian TTP patients, to evaluate disease relapse and mortality rate and their associated risk factors. Materials and Methods : This study was a cohort study of patients diagnosed with microangiopathic hemolytic anemia admitted to the Shariati Hospital, Tehran, a referral center for TTP patients, from 2010 to 2017. Demographic, clinical, and laboratory data were recorded and patients were followed for 3 years regarding disease relapse and mortality. Results :  114 patients (80 females, 34 males) with a mean age of 39.3 ± 14.99 years were included.  Hematologic and neurologic symptoms were the most common manifestations. Abnormal laboratory findings at the presentation included thrombocytopenia, anemia, and elevated LDH. All patients were treated with plasma exchange, and 75.5% of them had a response to treatment, while the 3-year relapse and mortality rate was 23.6 and 26.3%.  Lower platelet count was a predictor of disease relapse. Age, hematological, or neurological initial presentation were associated with TTP mortality. Conclusion : Based on the largest study of TTP patients ever in Iran, the demographic and clinical characteristics of Iranian TTP patients are similar to other existing reports. Knowledge of the risk factors for TTP relapse and mortality could be useful to alert hematologists for prompt therapeutic actions when necessary., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Tehran University of Medical Sciences.)

Vincristine (VCR) as a key drug for the treatment of acute lymphoblastic leukemia (ALL) is associated with neurotoxicity. We present a young man with a history of controlled childhood seizures who was diagnosed with pre-B-cell ALL and developed generalized tonic-clonic seizures following the Cancer and Leukemia Group B (CALGB) 8811 regimen. The patient also received oral itraconazole to prevent fungal infection initiated by chemotherapy. Possible causes of seizure, including electrolyte abnormalities, hypoglycemia, central nervous system infection or inflammation, were ruled out. According to the Naranjo Adverse Drug Reaction Scale, the patient's seizure had been attributed to VCR, possibly secondary to concomitant use of itraconazole and doxorubicin. The patient successfully recovered after discontinuation of VCR and supportive care. Clinicians should be aware of the possibility of vincristine-induced seizure in adult patients, especially with the concomitant use of drugs known to have potential drug-drug interactions., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Hemorrhagic cystitis (HC) is an important adverse event experienced after hematopoietic stem cell transplantation (HSCT). Severe HC could lead to significant morbidity, prolonged hospitalization with increased health-care costs, and may cause considerable mortality., Objectives: In order to investigate the influence of different contributing factors other than BK viruria on HC occurrence in a homogenous population, we retrospectively analyzed the potential risk factors., Study Design: We conducted a retrospective study among 200 patients (median age 12.4 years, IQR: 7.9-16.1) with acute leukemia who received peripheral blood allogenic HSCT after radiation-free myeloablative conditioning regimen, in pediatric cell therapy department of Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Tehran, Iran, between December 2014 and December 2021. Associations between risk factors and outcomes were examined by univariable and multivariable logistic regression models., Results: A total of 46 patients (23%) had developed HC during the study period. The median onset of HC was 29 (IQR: 24-37) days post-transplant, and it persisted for a median of 33 (7-270) days. The incidence of HC in our patients was estimated to be 3 in 1000 cases (95% CI: 2-4). The results of multivariable logistic model shows that the chance of HC in T-cell acute lymphoblastic leukemia (ALL) compared to B-cell All is nearly five times more (OR = 4.88; 95%CI: (1.51-15.78), P = 0.008). The incidence of HC in patients who underwent HSCT from haploidentical donors was significantly higher than full matched donors (P < 0.001). Undergoing transplant from a matched unrelated and haploidentical donor both augment the chance of HC in about six times more than matched related donors (OR = 6.36; 95%CI: (1.58-25.49), P = 0.009 and OR = 5.7; 95%CI: (1.83-17.75), P = 0.003, respectively). In patients who developed HC compared to non-HC group, overall survival was much worse (P < 0.001)., Discussion: Most studies have failed to demonstrate any relationship between late-onset HC and the dose of cyclophosphamide. In our study, although the dose of cyclophosphamide was similar in HSCT from MRD and MUD, the hazard of HC incidence was significantly higher in the latter group. This could be accredited to ATG, as in patients in the MRD group who had not received any ATG, the incidence of HC was much lower than the patients who had underwent HSCT from MUD or haploidentical donor group., Conclusions: Patients with T-cell ALL and those who under haploidentical HSCT had the highest incidence of HC., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

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.

Background: Docetaxel is a clinically well established antimitotic chemotherapy medication. Labeled docetaxel indications are breast cancer, gastric cancer, head and neck cancer, non-small cell lung cancer, and prostate cancer., Objective: This is a Phase IV study to evaluate the safety profile of docetaxel (Alvotere; NanoAlvand, Iran) in Iranian patients diagnosed with different types of cancers receiving chemotherapy regimens with docetaxel., Methods: Patients who received Alvotere as a part of their chemotherapy regimen were enrolled in this Phase IV, observational, multicenter, open-label study. Alvotere was administrated as a single agent or in combination with other chemotherapy agents. Safety parameters in each cycle were assessed, and the related data were recorded in booklets., Findings: A total of 411 patients with different types of cancers were enrolled from 25 centers in Iran. The most common malignancies among participants were breast cancer (49.88%), followed by gastric cancer (22.63%). Participants' mean age was 53.33 years, and the mean total dose used in each cycle was 132 mg. According to the results, 341 patients experienced at least 1 adverse event, that the most common was alopecia (41.12%). In total, 92 (22.38%) patients had at least 1 adverse event of grade 3 or 4, and 25 (6.08%) patients showed 54 serious adverse events, which the causality assessment for all was possibly related to Alvotere. There was a significant difference between men and women in the incidence of skin and subcutaneous tissue disorders (55.63% in women vs 41.73% in men; P  = 0.009). Also, the incidence of gastrointestinal disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatic enzymes increase, and fluid retention was significantly higher ( P < 0.05) in patients receiving anthracyclines in their chemotherapy regimens., Conclusions: The findings of this open-label, observational, multicenter, postmarketing surveillance showed that Alvotere appears to have an acceptable safety profile in Iranian cancer patients receiving chemotherapeutic regimens. ( Curr Ther Res Clin Exp . 2022; 82:XXX-XXX) © 2022 Elsevier HS Journals, Inc., Competing Interests: N. Anjidani is head of the medical department of OrchidPharmed company, which is in collaboration with NanoAlvand in respect to conducting clinical trials. The authors have indicated that they have no other conflicts of interest regarding the content of this article., (© 2021 Published by Elsevier Inc.)

Background: Finding a suitable donor at the optimal time is one of the most challenging issues in many transplant centers. We evaluated the clinical outcomes of 248 patients with acute leukemia and without matched sibling donors (MSD) who underwent alternative transplantation, including haploidentical (n=118), 10/10 matched unrelated (MUD, n=91), 9/10 mismatched unrelated (MMUD, n=21), and 9/10 mismatched related (MMRD, n=18) between January 2010 and November 2019 in our center. Materials and Methods : The myeloablative conditioning regimen was used in most of the patients. Both post-transplant cyclophosphamide (40mg/kg at +3, +4) and pre-transplant ATG were used in most of haploidentical transplantations. Patients with unrelated donors received ATG as a part of the conditioning regimen. Results: The median follow-up was 31.83 months. No significant difference in probability of 3-year leukemia- free survival (LFS) and overall survival (OS) as well as 3-year relapse incidence (RI) was noted among donor sources. A significant difference was found in the 3-year cumulative incidence (CI) of non-relapse mortality (NRM) among the donor sources: 37.89%, 24.20%, 24.30%, and 11.48%, for haplo, 9/10 MMUD, 10/10 MUD, and 9/10 MMRD (p=0.02). Using the multivariable Cox model, the advanced age of patients and Major-ABO mismatched were two risk factors independently associated with lower OS and DFS as well as higher NRM, whereas male donor and AML disease compared to ALL were associated with a better OS and DFS. Conclusion: No significant differences were observed in the overall outcome of haplo with other alternative transplantations, suggesting that haploidentical transplantation is a suitable, accessible, and inexpensive option., (Copyright © 2021 Tehran University of Medical Sciences.)

Competing Interests: Competing interests: The authors declare no conflict of Interest.

Background: Imatinib mesylate has revolutionized the treatment of patients with chronic myeloid leukaemia (CML); however, some patients fail to respond and have a poor prognosis. Evaluation of molecular response to imatinib is a sensitive method can help physicians make better and quicker therapeutic decisions in the course of this disease. This study aims to evaluate the molecular response to generic imatinib in Iranian patients with CML., Patients and Methods: This prospective study consisted of 255 newly diagnosed patients with CML who received imatinib. Molecular response was analyzed at 3 and 6 months from the start of the treatment and then every 6 months, and long-term outcomes, including overall survival (OS) and progression-free survival (PFS), were evaluated., Results: At a median follow-up of 34.8 months (range, 3-84 months, (the OS and PFS at 7 years were 94.3% and 92.9%, respectively. Eighty-four-month PFS rates in patients with a BCR-ABLIS ≤ 10% at 3 months and BCR-ABLIS ≤ 1% at 6 months were significantly higher than patients who did not obtain these levels of BCR-ABL transcripts (P = .004 and P < .0001, respectively). The proportion of patients who achieved major molecular response (MMR) was 44.1%, 52.97%, and 60.75% at 12, 18, and 24 months, respectively. At 12, 18, and 84 months, the PFS rates in patients who achieved MMR were significantly higher than in patients who did not achieve MMR (P = .002, P < .0001, and P = .003, respectively)., Conclusions: The data of this prospective study are highly comparable with that from clinical trials and prospective international studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Breast cancer is the second leading cause of death due to cancer in women. Triple negative breast cancer (TNBC) is a subgroup with unique behavior. There is a controversy in organ involvement in metastasis. In this study, we planned to define the prognostic factors, survival, and recurrence incidence of patients., Materials and Method: Among the 583 patients with breast mass referred to hematology and oncology clinic in Shariati hospital, Tehran, Iran from March 2005 to March 2015, fifty four patients entered the survival analysis whom we followed for two years until March 2017. Overall survival (OS) and disease-free survival (DFS) and Cumulative recurrence incidences (RI) were estimated. Univariate and multivariate Cox proportional hazards regression was performed to assess risk factors in predicting OS and DFS., Results: Median follow up for the patients was 5.00 years. The five-year OS, DFS and RI were 86.13% (95% CI (71.42-93.59), 63.09% (95% CI (47.04-75.49) and 32.15% (95% CI (19.52-47.43) respectively. Among the factors studied OS, DFS and RI differed significantly only between patients with and without nodal involvement (P = 0.004, P = 0.003, and P = 0.02 respectively). On the other hand, based on the univariate modeling, patients with nodal involvement had a higher risk of breast cancer-specific death (HR: 17.99, P = 0.004). Furthermore, patients with nodal involvement had a higher risk of breast cancer-specific death or recurrence (HR = 5.64, P = 0.008). In Multivariate model, just the nodal involvement significantly changed the hazard for OS (HR = 23.91, P = 0.001). As the nodal involvement was the only significant risk factor at the 0.2 level of significance, we can consider the hazard ratio of lymph node positivity in DFS univariate models as adjusted hazard., Conclusion: The only factor with significant effect on OS, DFS and RI was nodal involvement in the pathology report., Competing Interests: The authors have declared that no competing interests exist.