A placebo-controlled, crossover trial to investigate the efficacy of tiotropium bromide or placebo added to usual care in stable symptomatic post-hematopoietic stem cell transplantation (HSCT) bronchiolitis obliterans syndrome (BOS).

BACKGROUND: Despite the fundamental progress in hematopoietic stem cell transplant, this treatment is also associated with complications. Graft-versus-host disease is a possible complication of HSCT. Bronchiolitis obliterans syndrome (BOS) is the pulmonary form of this syndrome. Due to the high morbidity and mortality rate of BOS, various studies have been conducted in the field of drug therapy for this syndrome, although no standard treatment has yet been proposed. According to the hypotheses about the similarities between BOS and chronic obstructive pulmonary disease, the idea of using tiotropium bromide as a bronchodilator has been proposed. METHOD/DESIGN: A randomized, double-blind, placebo-controlled, and crossover clinical trial is being conducted to evaluate the efficacy of tiotropium in patients with BOS. A total of 20 patients with BOS were randomly assigned (1:1) to receive a once-daily inhaled capsule of either tiotropium bromide (KP-Tiova Rotacaps 18 mcg, Cipla, India) or placebo for 1 month. Patients will receive tiotropium bromide or placebo Revolizer added to usual standard care. Measurements will include spirometry and a 6-min walking test. ETHICS/DISSEMINATION: This study was approved by the Research Ethics Committees of Imam Khomeini Hospital Complex, Tehran University of Medical Science. Recruitment started in September 2022, with 20 patients randomized. The treatment follow-up of participants with tiotropium is currently ongoing and is due to finish in April 2024. The authors will disseminate the findings in peer-reviewed publications, conferences, and seminar presentations. TRIAL REGISTRATION: Iranian Registry of Clinical Trial (IRCT) IRCT20200415047080N3. Registered on 2022-07-12, 1401/04/21.

Investigating the effect of pre-transplant thrombocytopenia and anemia on the engraftment and long-term survival in multiple myeloma patients.

BACKGROUND: Autologous stem cell transplantation (ASCT) following high-dose melphalan is the standard treatment for Multiple Myeloma (MM). Despite new treatments, further investigation is needed to identify prognostic factors of ASCT. This study evaluated the impact of thrombocytopenia and anemia on the engraftment of MM patients after ASCT. MATERIALS AND METHODS: This retrospective study involved 123 MM patients who underwent ASCT with high-dose Melphalan. Successful engraftment is achieved when both platelets (Plt) and white blood cells (WBC) engraft successfully. We examined the statistically significant cut-offs for the prognostic factors on the admission day. Ultimately, the association of risk factors with the Plt and WBC engraftment and long-term survival were analyzed as the outcomes of interest. RESULTS: Spearman's correlation coefficient between Plt and WBC engraftment was 0.396 (p < 0.001). The engraftment in the patients with Plt < 140,000/µL was 17.4% slower (p = 0.036) and the odds of long-term survival was 72% lower (p = 0.016) than in patients with higher Plt. Patients with Hb < 11 g/dL were 12.7% slower in engraftment. Age over 47 was a significant factor in slower engraftment (p = 0.036) which decelerated the engraftment by 15.2%. CONCLUSION: Thrombocytopenia and anemia before transplantation are related to slower Plt/WBC engraftment and as prognostic factors might predict the long-term survival of MM patients following ASCT.

Association between nutritional status and biochemical markers among hematopoietic stem cell transplant candidates: a cross-sectional study.

AIM: Candidates of Hematopoietic Stem Cell Transplantation (HSCT) may be at nutritional risk due to decreased oral intake, high nutritional requirements and nutrient malabsorption. The aim of this study was to evaluate the association between nutritional status and blood biomarkers in candidates of HSCT. METHODS: A total of 278 patients aged 18-65 years old were recruited and their baseline demographic and clinical characteristics were recorded. All subjects underwent nutritional status analysis using Nutritional Risk Screening (NRS-2002). Blood biomarkers including C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), hemoglobin, albumin and total protein as well as CRP-albumin ratio (CAR) and Body Mass Index (BMI) were measured and compared between two groups based on Nutritional Risk Screening (NRS-2002) within 24 h of admission in Bone Marrow Transplant ward. RESULTS: The results showed that undernourished patients (NRS ≥ 3) had significantly higher inflammatory markers including ESR, CRP and CAR as well as lower BMI and serum albumin and hemoglobin concentrations (P < 0.05); however, no significant association was observed in terms of total protein even after adjusting for confounders (P > 0.05). CONCLUSIONS: This study revealed that BMI combined with biochemical markers are the appropriate parameters for assessment of nutritional status in HSCT candidates. Furthermore, the nutritional status was verified to be significantly associated with systematic inflammation.

Maintenance therapy with Everolimus in patients with refractory or relapsing Hodgkin lymphoma after autologous stem cell transplantation.

Introduction: Patients with relapsing or primary refractory Hodgkin lymphoma, still have unsatisfactory outcomes after high dose chemotherapy followed by autologous stem cell transplantation (ASCT). Brentuximab Vedotin (BV) is the only approved agent for maintenance therapy for up to one year in these patients, however, this agent is often not available or affordable for many patients, especially in the developing countries. In this study, we used Everolimus as maintenance therapy after ASCT among patients with relapsing/refractory Hodgkin lymphoma. Materials and Methods: We collected the data of 20 patients with primary refractory or relapsing Hodgkin lymphoma who had undergone ASCT between June 2016 and June 2021. Everolimus was started at 10 mg daily on day +90 after ASCT for at least two years in patients with stable disease status, confirmed by imaging modalities. Patients were followed for disease status and drug side effects every 3 months. Results: In our single-arm case-series study, the median duration of treatment was 22.95 months. Except for three patients, who had progression, others had no progression and are still receiving Everolimus (85%). No serious side effect was seen. We had no mortality due to disease recurrence. Conclusion: Until now, results showed promising effects of Everolimus in patients with relapsing or primary refractory Hodgkin lymphoma as maintenance therapy after ASCT.

Therapeutic effect of trace elements on multiple myeloma and mechanisms of cancer process.

In the human body, trace elements and other micronutrients play a vital role in growth, health and immune system function. The trace elements are Iron, Manganese, Copper, Iodine, Zinc, Cobalt, Fluoride, and Selenium. Estimating the serum levels of trace elements in hematologic malignancy patients can determine the severity of the tumor. Multiple myeloma (MM) is a hematopoietic malignancy and is characterized by plasma cell clonal expansion in bone marrow. Despite the advances in treatment methods, myeloma remains largely incurable. In addition to conventional medicine, treatment is moving toward less expensive noninvasive alternatives. One of the alternative treatments is the use of dietary supplements. In this review, we focused on the effect of three trace elements including iron, zinc and selenium on important mechanisms such as the immune system, oxidative and antioxidant factors and cell cycle. Using some trace minerals in combination with approved drugs can increase patients' recovery speed. Trace elements can be used as not only a preventive but also a therapeutic tool, especially in reducing inflammation in hematological cancers such as multiple myeloma. We hope that the prospect of the correct use of trace element supplements in the future could be promising for the treatment of diseases.

Gut microbiota intervention by pre and probiotics can induce regulatory T cells and reduce the risk of severe acute GVHD following allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Acute graft-versus-host disease (aGVHD) is one of the leading causes of limitation and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Numerous studies have shown that changes in the gut microbiome diversity increased post-transplant problems, including the occurrence of aGVHD. Probiotics and prebiotics can reconstitute the gut microbiota and thus increase bacterial metabolites such as short-chain fatty acids (SCFAs) that have immunomodulatory effects preventing aGVHD in recipients of allo-HSCTs. METHODS/STUDY DESIGN: We conducted a pilot randomized clinical trial to investigate whether oral synbiotics are associated with the prevention or reduction in occurrence/severity and mitigate complications of aGVHD following allo-HSCT. A commercially available synbiotic mixture containing high levels of 7 safe bacterial strains plus fructo-oligosaccharides as a prebiotic was administered to allo-HSCT recipients. Out of 40 allo-HSCT patients, 20 received daily a synbiotic 21 days prior to transplantation (days -21 to day 0). In contrast, in the control group 20 recipients of allo-HSCT did not receive a symbiotic therapy. RESULTS: Within first 100 days of observation, the incidence of severe (grade III/IV) aGVHD in the a synbiotic-therapy group was 0% (0 out of 20 patients), whereas it was 25% (5 out of 20 patients) in the control group (P = 0.047). The median percentage of CD4 + CD25 + Foxp3+ regulatory T cells (Tregs) among CD4+ lymphocytes on day 28 after HSCT in the synbiotic group was higher (2.54%) than in control group (1.73%; P = 0.01). There was no difference in Treg cells on day 7 after HSCT between two groups. However, the median percentage and the absolute count of Tregs in patients who experience aGVHD was significantly lower on days 7 and 28 after HSCT (both P < 0.05). The overall 12-month survival (OS) rate was higher (90%) in the symbiotic-treated patients than in the control group (75%), but the difference was not statistically significant (P = 0.234). CONCLUSION: Our preliminary findings suggest that synbiotic intake before and during the conditioning regimen of allo-HSCT patients may lead to a reduction in the incidence and severity of aGVHD through the induction of CD4 + CD25 + Foxp3+ regulatory T cells, thus contributing to the improvement of transplant outcomes. Much larger studies are needed to confirm our observations.

Survival of Patients with Acute Myeloid Leukemia after Allogeneic Stem Cell Transplantation: An Experience in Developing Country.

Background: Allogeneic stem cell transplantation (allo-SCT) is the highest potential treatment for long-term survival as post-remission therapy for acute myeloid leukemia (AML). The aim of this study was to estimate the overall survival (OS) of patients with AML after allo-SCT and to identify the factors affecting them as a prognostic factor for the survival of patients. Material and Methods: In this retrospective cohort study, data of patients with AML who underwent allo-SCT at Taleghani bone marrow transplantation and cell therapy center in Tehran, Iran, from May 2009 to September 2016 were used. A total of 101 patients were enrolled and death time was considered as a failure event for them. Kaplan-Meier method, log-Rank tests, and Cox proportional hazard model were used to evaluate OS and to identify the risk factors of patient's survival. The SPSS software version 21 was used for the analysis of data and P<0.05 was considered as a significant level. Results: Of 101 patients with AML, 49 (48.5%) were males. The median age at allo-SCT was 32.76 years and 42 patients (41.6%) died. The 5-year OS and disease-free survival (DFS) was 56% (95%CI: 51-61%) and 52% (95%CI: 57-47%), respectively. Multivariate analysis by Cox regression indicated that OS has a significant relationship with primary WBC count and relapse (P=0.001). Conclusion: Our results showed that allo-SCT has nearly the same outcome in developing countries and the WBC count and relapse are effective factors on the chance of survival in AML patients after allo-SCT.

Azithromycin oral suspension in prevention and management of oral mucositis in patients undergoing hematopoietic stem cell transplantation: a randomized controlled trial.

OBJECTIVES: This study aimed to investigate the effects of azithromycin suspension on oral mucositis in patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS AND MATERIAL: The study was designed as a single-blind randomized controlled trial in Taleghani medical center affiliated to Shahid Beheshti University of Medical Sciences Tehran Iran. Patients undergoing HSCT were randomly assigned to intervention or control groups. Azithromycin suspension was administered twice daily by gargling for 30 s and swallowing, on the first day of chemotherapy for patients in the intervention group. Graded oral mucositis (OM) occurrence based on National Cancer Institute Common Toxicity Criteria (NCI-CTC) scale (grade 0 to 5) was considered the main outcome, and the Numerical Rating Scale (NRS:0-10) measured the severity of OM symptoms. RESULTS: In a duration of 15 months, 88 patients were randomly assigned and finally 70 patients were evaluable for study outcomes (randomized 1:1 to azithromycin versus no-azithromycin). The incidence and duration of the mucositis significantly improved in the intervention group compared to the control. Azithromycin use was consistent with a lower rate of dryness (P < 0.001), dysphagia (P < 0.001), and loss of sense of taste (P < 0.001). Also, in the intervention group, lower intensity of pain due to mucositis (P = 0.01) and lower duration of mucositis were observed (p = 0.045). No significant adverse drug reaction was observed in patients receiving azithromycin. CONCLUSION: Based on the result from this study, azithromycin suspension is an effective option in the prevention and treatment of chemotherapy-induced OM. Further study is needed to assess the effect of azithromycin and comparison with other therapeutic options. TRIAL REGISTRATION: Iranian Registry of Clinical Trials: IRCT201603093210N13.

Phosphatidylinositol 3-kinase signaling inhibitors for treatment of multiple myeloma: From small molecules to microRNAs.

Multiple myeloma is one of the most hard-to-treat cancers among blood malignancies due to the high rate of drug resistance and relapse. The researchers are trying to find more effective drugs for treatment of the disease. Hence, the use of drugs targeting signaling pathways has become a powerful weapon. Overactivation of phosphatidylinositol 3-kinase signaling pathways is frequently observed in multiple myeloma cancer cells, which increases survival, proliferation, and even drug resistance in such cells. In recent years, drugs that inhibit the mediators involved in this biological pathway have shown promising results in the treatment of multiple myeloma. In the present study, we aimed to introduce phosphatidylinositol 3-kinase signaling inhibitors which include small molecules, herbal compounds, and microRNAs.

Treatment Failure in Acute Myeloid Leukemia: Focus on the Role of Extracellular Vesicles.

Acute myeloblastic leukemia (AML) is one of the most common types of blood malignancies that results in an AML-associated high mortality rate each year. Several causes have been reported as prognostic factors for AML in children and adults, the most important of which are cytogenetic abnormalities and environmental risk factors. Following the discovery of numerous drugs for AML treatment, leukemic cells sought a way to escape from the cytotoxic effects of chemotherapy drugs, leading to treatment failure. Nowadays, comprehensive studies have looked at the role of extracellular vesicles (EVs) secreted by AML blasts and how the microenvironment of the tumor changes in favor of cancer progression and survival to discover the mechanisms of treatment failure to choose the well-advised treatment. Reports show that malignant cells secrete EVs that transmit messages to adjacent cells and the tumor's microenvironment. By secreting EVs, containing immune-inhibiting cytokines, AML cells inactivate the immune system against malignant cells, thus ensuring their survival. Also, increased secretion of EVs in various malignancies indicates an unfavorable prognostic factor and the possibility of drug resistance. In this study, we briefly reviewed the challenges of treating AML with a glance at the EVs' role in this process. It is hoped that with a deeper understanding of EVs, new therapies will be developed to eliminate the relapse of leukemic cells.

Pre-and Post-Transplant Serum Lactate Dehydrogenase Levels as a Predictive Marker for Patient Survival and Engraftment in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

BACKGROUND: The discovery of biomarkers to predict the development of complications associated with hematopoietic stem cell transplantation (HSCT) offers a potential avenue for the early identification and treatment of these life-threatening consequences. Serum lactate dehydrogenase (sLDH) has been identified as a potential biomarker for determining the outcome of allogenic HSCT (allo-HSCT). METHODS: A retrospective study was performed using data collected from 204 allo-HSCT recipient patients to examine the predictive value of sLDH levels pre- and post-allo-HSCT on patient survival, graft-versus-host-disease (GVHD) incidence, and time to platelet/white blood cells (WBC) engraftment. RESULTS: Our findings show that neither pre- (p= 0.61) nor post-transplantation (p= 0.55) sLDH levels were associated with GVHD incidence. However, elevated sLDH levels pre- and post-transplantation (≥ 386 and ≥ 409 IU/mL, respectively) were found to be adverse risk factors for patient survival (p= 0.16, p= 0.20, respectively). Furthermore, a median sLDH level ≥ 400 IU/mL from day +5 to day +15 post-transplantation had a significant positive association with enhanced time to platelet and white blood cell (WBC) engraftment, compared to patients with sLDH levels < 400 IU/mL (p< 0.001). CONCLUSION: Our data suggests that high sLDH levels pre- and post-allo-HSCT could be considered a predictor of poor patient survival. Furthermore, high levels of sLDH days 5-15 post-allo-HSCT could be associated with improved time to platelet and WBC engraftment; however, this appears to come at the cost of increased mortality risk.

Association of HScore Parameters with Severe COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Several reports have associated the severe Coronavirus disease-2019 (sCOVID-19) with secondary-hemophagocytic lymphohistiocytosis (sHLH) and proposed utilizing the hemophagocytic syndrome diagnostic score (HScore) for sCOVID-19 patients. We conducted a systematic review and meta-analysis to find the possible association of HScore parameters with severity in COVID-19 patients. METHODS: A systematic search was performed in Medline via PubMed, EMBASE, and Cochrane databases using all HScore and COVID-19 keywords. The studies were all from 2020, and the study language was limited to English. The records were screened based on inclusion/exclusion criteria. Random/fixed-effect models were employed for meta-analysis, based on the I2 index of parameters. The pooled mean differences were estimated for continuous parameters. The pooled odds-ratio was estimated for fever. The level of significance was set at 0.05. RESULTS: Eighteen studies (comprising 2459 patients) out of 26151 screened studies were included in this meta-analysis. The results showed that the level of leukocyte, neutrophil, aspartate transaminase (AST), ferritin, and fibrinogen were significantly higher in sCOVID-19 patients than in non-severe ones. Significant lower levels of lymphocyte, platelet, and hemoglobin were also found in sCOVID-19 patients than non-severe patients. Fever was nearly associated with two times increased odds of sCOVID-19 (P=0.051). CONCLUSION: Lymphopenia, thrombocytopenia, hypohemoglobinemia, hyperferritinemia, high levels of AST, and fever are common features of both sCOVID-19 and HLH. However, the leukocytosis, neutrophilia, and hyperfibrinogenemia found in sCOVID-19 are in contrast with HScore. Conclusively, HScore parameters could be risk factors for sCOVID-19. However, some parameters' roles are contradictory, suggesting the need for further investigation and a new way of HScore interpretation in sCOVID-19 patients.A preprint of this study was published at https://www.researchsquare.com/article/rs-54490/v2.

Immunotherapy with adoptive cytomegalovirus-specific T cells transfer: Summarizing latest gene engineering techniques.

Cytomegalovirus (CMV) infection remains a major complication following allogeneic hematopoietic stem cell transplantation (HSCT). T cell response plays a critical role in inducing long-term immunity against CMV infection/reactivation that impairs during HSCT. Adoptive T cell therapy (ACT) via transferring CMV-specific T cells from a seropositive donor to the recipient can accelerate virus-specific immune reconstitution. ACT, as an alternative approach, can restore protective antiviral T cell immunity in patients. Different manufacturing protocols have been introduced to isolate and expand specific T cells for the ACT clinical setting. Nevertheless, HLA restriction, long-term manufacturing process, risk of alloreactivity, and CMV seropositive donor availability have limited ACT broad applicability. Genetic engineering has developed new strategies to produce TCR-modified T cells for diagnosis, prevention, and treatment of infectious disease. In this review, we presented current strategies required for ACT in posttransplant CMV infection. We also introduced novel gene-modified T cell discoveries in the context of ACT for CMV infection. It seems that these innovations are enabling to improvement and development of ACT utilization to combat posttransplant CMV infection.

Oncolytic virotherapy in hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) is a curative option for various hematologic malignancies. However, fatal complications, such as relapse and graft-versus-host disease (GVHD) hampered favorable HSCT outcomes. Cancer cells remained in the body following the conditioning regimen, or those contaminating the autologous graft can cause relapse. Although the relapse is much lesser in allogeneic HSCT, GVHD is still a life-threatening complication in this type of HSCT. Researchers are seeking various strategies to reduce relapse and GVHD in HSCT with minimum effects on the engraftment and immune-reconstitution. Oncolytic viruses (OVs) are emerging anti-cancer agents with promising results in battling solid tumors. OVs can selectively replicate in the malignant cells in which the antiviral immune responses have defected. Hence, they could be used as a purging agent to eradicate the tumoral contamination of autologous grafts with no damages to hematopoietic stem cells. Moreover, they have been shown to alleviate GVHD complications through modulating alloreactive T cell responses. Primary results promise using OVs as a strategy to reduce both relapse and GVHD in the HSCT without affecting hematologic and immunologic engraftment. Herein, we provide the latest findings in the field of OV therapy in HSCT and discuss their pros and cons.

An Intelligent Clinical Decision Support System for Predicting Acute Graft-versus-host Disease (aGvHD) following Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Acute graft-versus-host disease (aGvHD) is a complex and often multisystem disease that causes morbidity and mortality in 35% of patients receiving allogeneic hematopoietic stem cell transplantation (AHSCT). OBJECTIVE: This study aimed to implement a Clinical Decision Support System (CDSS) for predicting aGvHD following AHSCT on the transplantation day. MATERIAL AND METHODS: In this developmental study, the data of 182 patients with 31 attributes, which referred to Taleghani Hospital Tehran, Iran during 2009-2017, were analyzed by machine learning (ML) algorithms which included XGBClassifier, HistGradientBoostingClassifier, AdaBoostClassifier, and RandomForestClassifier. The criteria measurement used to evaluate these algorithms included accuracy, sensitivity, and specificity. Using the machine learning developed model, a CDSS was implemented. The performance of the CDSS was evaluated by Cohen's Kappa coefficient. RESULTS: Of the 31 included variables, albumin, uric acid, C-reactive protein, donor age, platelet, lactate Dehydrogenase, and Hemoglobin were identified as the most important predictors. The two algorithms XGBClassifier and HistGradientBoostingClassifier with an average accuracy of 90.70%, sensitivity of 92.5%, and specificity of 89.13% were selected as the most appropriate ML models for predicting aGvHD. The agreement between CDSS prediction and patient outcome was 92%. CONCLUSION: ML methods can reliably predict the likelihood of aGvHD at the time of transplantation. These methods can help us to limit the number of risk factors to those that have significant effects on the outcome. However, their performance is heavily dependent on selecting the appropriate methods and algorithms. The next generations of CDSS may use more and more machine learning approaches.

Adverse Effects of Busulfan Plus Cyclophosphamide versus Busulfan Plus Fludarabine as Conditioning Regimens for Allogeneic Bone Marrow Transplantation.

BACKGROUND: The side effects of conditioning regimens on the success rate of allogeneic transplantation around the world have been challenging. In this study, we aimed to investigate the side effect of Bu/Cy and Bu/Flu regimens on our patients who underwent allogeneic bone marrow transplantation. METHODS: We analyzed 180 patients receiving bone marrow transplantation in Taleghani Hospital, in Tehran, Iran between April 2016 and December 2019. Patients in group A received a combination of intravenous busulfan 0.8 mg/kg QID over two hours for 4 consecutive days (12.8 mg/kg in total)(Savani et al., 2006) and cyclophosphamide 60 mg/kg per day for two consecutive days. Patients in group B received busulfan the same as the first group in combination with fludarabine equal to 40 mg/m² per day. Patients were followed up at regular intervals up to two years after transplantation. RESULT: Various items were evaluated for patients, including cardiopulmonary function, psychological disorders, GVHD, and endocrine disorders such as hypothyroidism, fertility, or gonad dysfunction.  Primary hypothyroidism developed in 13.3% and 11.1% of the Bu/Cy and Bu/Flu groups, respectively (p=0.230). None of the patients in either group experienced infertility or gonad dysfunction. In group A versus group B, pulmonary diseases were detected in  4.4% versus 6.6% of BMT recipients, respectively (p = 0.223). In both groups, mitral and tricuspid regurgitation were observed in patients (8.9% vs. 11.1%; p = 0.189). Incidence of Psychological disorders was no significant difference between the two groups. 32.2% of group A versus 34.45%  of group B had skin and liver GVHD, respectively (p = 0.235). CONCLUSION: The therapeutic-related adverse effects of the two conditioning regimens in patients who underwent allogeneic bone marrow transplant were almost similar. To improve quality of life and overall survival among BMT patients, careful evaluation of treatment-related complications should be part of the regular follow-up of them.

PI3 kinase signaling pathway in hematopoietic cancers: A glance in miRNA's role.

Hematopoietic cancers are among the most common malignancies worldwide, which are divided into different types depending on the origin of tumor cells. In recent years, the pivotal role of different signaling pathways in the onset and progression of these cancer types has been well established. One of these pathways, whose role in blood malignancies has been well-defined, is PI3K/mTOR/AKT axis. The signaling pathway involves in a wide variety of important biological events in cells. It is clear that dysregulation of mediators involved in PI3 kinase signaling takes a pivotal role in cancer development. Considering the undeniable role of miRNAs, as one of the well-known families of non-coding RNAs, in gene regulation, we aimed to review the role of miRNAs in regulation of PI3 kinase signaling effectors in hematopoietic cancers.

The Evaluation of Melatonin Effects on Mobilization and Engraftment in Autologous Hematopoietic Stem Cell Transplant Recipients; A Randomized, Double-blind and Placebo-controlled Trial.

Mobilization and engraftment of Hematopoietic Stem Cells (HSCs) are challenging issues in Autologous HSC transplantation (AHSCT) so several attempts such as colony-stimulating factors (CSF) and plerixafor have been used for enhancement of HSCs mobilization and engraftment. In this randomized, double-blind and placebo-controlled study, we evaluated the melatonin's efficacy and safety, as endogenous CSF inducer, co-administered with Filgrastim in mobilizing and engraftment of HSC. AHSCT patients were randomized to receive either Melatonin or placebo plus filgrastim. Of Fifty-one patients, 26 patients received the melatonin (In mobilization phase 3 mg sublingual twice daily, then 9 mg single dose 30 min before apheresis session and then 3 mg twice daily from +1 until engraftment) and 25 patients received the placebo. The mean number of CD34 cells/kg × 106 in the melatonin group was 6.54 versus 4.22 in the placebo group (p = 0.025). The mean day to neutrophil engraftment in the melatonin group was 11.69 ± 2.093, whereas 12.68 ± 2.42 days in the placebo group (p = 0.021). In this study, the second apheresis session requirement, the use of plerixafor and hospital stay duration, were comparable between the two groups. Considering the result of the study, it could be suggested that melatonin plus Filgrastim can be effectively used in AHSCT patients to enhance the number of peripheral CD34 cells/kg × 106 and decrease the day number of neutrophil engraftment.

Risk Factors of Graft-Versus-Host Disease in the Iranian Allogeneic Hematopoietic Stem Cell Transplantation: A 10-Year Experience.

Background: Graft-versus-host disease (GVHD) is a serious complication associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thus, it is necessary to evaluate the risk factors of GVHD in allo-HSCT. Herein, we studied the effects of some risk factors on GVHD incidence in patients with allo-HSCT. Methods: We retrospectively evaluated the GVHD incidences and risk factors in 199 patients diagnosed with hematological disorders who underwent allo-HSCT in Taleghani hospital, Tehran, Iran, between 2007 and 2017. The univariable and multivariable analyses of time to event data were performed using the Logistic regression model. Computations were performed using SAS, and the level of statistical significance for univariable and multivariable analyses was set at 20% and 10%, respectively. Results: Acute GVHD (aGVHD) was seen in 59 (29.6%) patients, and 18 (9%) patients developed chronic GVHD (cGVHD). The odds of GVHD incidence in male to female transplants was 3.49 times greater than the male-to-male transplantations (CI, 1.16, 11.5; p<0.001). The patients with body mass index (BMI) below 18.5 had 96% lower odds of GVHD incidence compared with those with BMI above 30 (CI, 0.007-0.27; p=0.013). The odds of GVHD incidence in patients who were negative for cytomegalovirus (CMV) antigen was 76% lower than patients with positive CMV antigen (CI, 0.06-0.93; p=0.081). Conclusion: In a nutshell, our results indicated that the donor-recipient gender disparity, the recipient's BMI, and CMV infection/reactivation status might be pivotal risk factors, which should be taken into account for prevention and management of GVHD.