Clinical Features and Risk Factors of Relapse and Mortality in Thrombotic Thrombocytopenic Purpura Patients: A Seven-Year Experience.

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.

Outcome of Peripheral Blood Allogeneic Hematopoietic Stem Cell Transplantation as a Treatment Option in Patients With Severe Aplastic Anemia Between 40 and 50 Years.

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.

Selection of Suitable Alternative Donor in the Absence of Matched Sibling Donor: A Retrospective Single-Center Study to Compare between Haploidentical, 10/10 and 9/10 Unrelated Donor Transplantation.

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.

Curcumin Combined with Thalidomide Reduces Expression of STAT3 and Bcl-xL, Leading to Apoptosis in Acute Myeloid Leukemia Cell Lines.

INTRODUCTION: 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.

Evaluation of Molecular Response to Imatinib Mesylate Treatment in Iranian Patients With Chronic Myeloid Leukemia.

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.

Platelet endothelial cell adhesion molecule-1 polymorphism in patients with bronchial asthma.

Asthma is considered as a chronic inflammatory airway disease and defined as increased tracheobronchial responsiveness to variety of stimuli. Edema and inflammatory cell infiltration in airway is observed in the asthmatic patients. One of the essential changes in inflammation is adhesion of leukocyte to endothelium and transmigration of leukocytes to the sites of inflammation. Unfortunately, little is known about the role of platelet endothelial cell adhesion molecule-1 (PECAM-1) polymorphism in asthma inflammatory process. The purpose of this study was to determine whether PECAM-1 polymorphisms affect the risk of asthma or not.Forty-five asthmatic patients (including 27 men and 18 women) and 45 healthy volunteers (11 men and 34 women) were studied. To determine the severity of the asthmas situation, a questionnaire was prepared asking the following information: age, sex, clinical signs and symptoms and past medical history. All subjects were genotyped for PECAM-1 polymorphism by using amplification refractory mutation system -polymerase chain reaction (ARMS-PCR). The genotype distribution of PECAM-1 80 Val/Met polymorphism in all asthmatic patients were Val/Val while non asthmatic controls were 95.6% Val/Val and 4.4% Val/Met. However, these differences were not statistically significant (p<0.05). The allele and genotype frequencies of PECAM-1 125 Val/Leu polymorphism were significantly different between asthmatic patients and controls. On the other hand, the presence of 125 Leu allele was associated with an increasing risk of asthma with an odds ratio of 2.8 (95% CI; 1.5-5.3, p=0.002). Our findings suggest that the PECAM-1 125 Val/leu polymorphism might be a genetic factor that may be associated with asthma.