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.

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.

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.

Effects of ABO incompatibility on the outcome of allogeneic hematopoietic stem cell transplantation.

BACKGROUND: ABO compatibility between donor and recipient is no necessary in allogeneic hematopoietic stem cell transplantation (AHSCT). Incompatible transplantations can be divided into three groups based on the donor and recipient blood groups. The influence of each kind of incompatibilities on the outcome of patients does not seem to be consistent. This study aimed to investigate the outcome of AHSCT patients focusing on compatibility statues. METHOD: This retrospective study was conducted on 186 patients who underwent first AHSCT, includes 108 identical, 38 minor, 32 major and eight bidirectionalABO incompatible recipients. Comparative analysis was performed for common clinical transplantation outcomes. RESULTS: There was no statistically significant association betweenABO incompatibility and graft-versus-host disease, WBC or platelet engraftment, and transfusion requirement. WBC engraftment rate was significantly lower in minor-incompatible patients. Furthermore, total and direct bilirubin which (the hemolysis biomarkers) were considerably higher in the bidirectional incompatible group, compared to the other patients. CONCLUSION: Our results indicate that theABO incompatibility might be an effective factor in engraftment time and laboratory hemolysis. Elucidating the impact of ABO incompatibility on the clinical outcome of patients warrants an extended and deep investigation in a large-scale study with comprehensive variables such as survival, relapse, and other complication of transplantation.

MicroRNAs modulating angiogenesis: miR-129-1 and miR-133 act as angio-miR in HUVECs.

The sprouting of new blood vessels by angiogenesis is critical in vascular development and homeostasis. Aberrant angiogenesis leads to enormous pathological conditions such as ischemia and cancer. MicroRNAs (also known as miRNAs or miRs) play key roles in regulation of a range of cellular processes by posttranscriptional suppression of their target genes. Recently, new studies have indicated that miRNAs are involved in certain angiogenic settings and signaling pathways use these non-coding RNAs to promote or suppress angiogenic processes. Herein, VEGFR2 and FGFR1 were identified as miR-129-1 and miR-133 targets using bioinformatic algorithms, respectively. Afterwards, using luciferase reporter assay and gene expression analysis at both mRNA and protein levels, VEGFR2 and FGFR1 were validated as miR-129-1 and miR-133 targets. In addition, we showed that miR-129-1 and miR-133 suppress angiogenesis properties such as proliferation rate, cell viability, and migration activity of human umbilical vein endothelial cells (HUVEC) in vitro. We conclude that these miRNAs can suppress key factors of angiogenesis by directly targeting them. These results have important therapeutic implications for a variety of diseases involving deregulation of angiogenesis, including cancer.

Analysis of dystrophin gene in Iranian Duchenne and Becker muscular dystrophies patients and identification of a novel mutation.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are the most frequent muscular dystrophies. Present study aimed to determine the frequency of dystrophin gene alterations in Iranian DMD/BMD patients using molecular techniques. 146 Iranian DMD/BMD patients have been analyzed using two devised sets of multiplex polymerase chain reaction (M-PCR) followed by multiple ligation-dependent probe amplification (MLPA). Two isolated DMD and BMD patients were analyzed by DNA sequencing. 30.9 % of patients had single-exon deletion while group and contiguous exon deletions were identified in 41 % of the patients. The most numerous exon deletions included exons 45-50 and were identified in the first M-PCR set. Deletion detection rate was 99 % in first M-PCR set and remaining deletions (1 %) were identified in the second M-PCR set. MLPA analysis showed that there were two exons 3-5 and 41-43 duplications (1.4 %) in a BMD and a DMD patient, respectively. Two nonsense mutations including c.633dupA and c.6283 C>T were, respectively, found in a DMD and BMD patient in which c.633dupA has not ever been reported in DMD mutation database and was pathogenic mutation. Besides the report of frequency of dystrophin gene alteration in a subset of Iranian DMD/BMD patients, it was revealed that the proposed M-PCR protocol can be useful in the initial step of molecular diagnosis of DMD/BMD. Exon sequencing would be the final step in determining the mutation status of DMD/BMD patients following MLPA.

The Association of HLA Class 1 and Class 2 Antigens with Multiple Myeloma in Iranian Patients.

OBJECTIVE: Multiple myeloma (MM) is a B-cell malignancy characterized by the clonal proliferation of malignant plasma cells. According to results of some studies, it has been suggested that the HLA class 1 and 2 genes have susceptibility effects on MM. Studies of different populations have reported different HLA class 1 and 2 alleles that affect MM. In this study, we assessed the association of HLA class 1 and class 2 antigens with MM in Iranian patients. MATERIALS AND METHODS: We performed a case-control genotyping study with 105 Iranian MM patients that were selected from the bone marrow transplantation department of Taleghani Hospital and 150 controls using single specific primer-polymerase chain reaction with the HLA-Ready Gene ABDR Kit. RESULTS: Our results demonstrated that 21% of patients versus 12% of controls and 11% of patients versus 3% of controls carried HLA-A*03 and HLA-B*18, respectively. The MM patients had a significant increase in the frequency of HLA-A*03 and HLA-B*18 alleles in comparison to control subjects (p=0.039, OR=2.057 and p=0.013, OR=3.567, respectively). CONCLUSION: Our findings suggested that the HLA-A*03 and HLA-B*18 alleles have significant susceptibility effects on MM in the Iranian population. However, compared to other populations, the above-mentioned alleles had different statuses. Since there are not many studies evaluating and calculating this association among ethnic groups, further studies among other populations are needed to explain the exact association of the HLA genes with MM.

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.

Efficacy and Safety of a DOAC Compared to Unfractionated Heparin and A Low Molecular Weight Heparin in the Prevention of Thromboembolism in Hematopoietic Stem Cell Transplant Recipients.

Background: Hematopoietic stem cell transplantation (HSCT) patients are at risk of thromboembolic events, making thromboprophylaxis crucial. Objectives: This study aimed to compare apixaban, a direct factor Xa inhibitor (DOAC), with dalteparin and unfractionated heparin for thromboprophylaxis in HSCT recipients. The safety outcome included the assessment of hemorrhagic events. Methods: In this open-label randomized clinical trial, 182 HSCT recipients were divided into three groups: Apixaban (n = 61, 2.5 mg two times a day), dalteparin (n = 59, 5000 IU daily), and unfractionated heparin (n = 62, 5000 IU twice daily). These anticoagulant regimens were administered after central vein catheterization and during hospitalization. The primary clinical outcome was the risk of thrombosis, and the secondary outcome was the rate of bleeding. Relevant laboratory results were analyzed using appropriate statistical tests. Results: Among the 61 patients in the apixaban group, six experienced thrombosis (9.83%), with four (6.65%) of them on anticoagulants. In the dalteparin group, three patients (5%) developed thrombosis, two of whom (3.38%) were on anticoagulants. In the heparin group, all four thrombosis cases (6.4%) occurred in patients on anticoagulants (P = 0.543 overall and P = 0.776 in anticoagulant users). Only two cases of bleeding were reported (1.09% overall), one in the dalteparin group (1.69%) and the other in the apixaban group (1.63%). Conclusions: Apixaban, dalteparin, and heparin demonstrated similar effectiveness in preventing thromboembolism in HSCT recipients. Furthermore, the comparison of bleeding rates across the study groups did not reveal significant differences. Larger studies with higher event rates may yield more precise conclusions.

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.

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.

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.

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.

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.

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.

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.

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.

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.