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.

All about blinatumomab: the bispecific T cell engager immunotherapy for B cell acute lymphoblastic leukemia.

INTRODUCTION: B cell acute lymphoblastic leukemia-lymphoma (B-ALL) accounts for approximately 75% of ALL cases and is observed in children and adults. Recent advances in disease diagnosis, stratification and prognostication have led to a better characterization of different subgroups of ALL. Notwithstanding the significant improvement in the complete remission rate of B-ALL, patients with minimal residual disease (MRD) and relapsed/refractory (R/R) settings suffer from poor outcomes. HYPOTHESIS: However, novel therapies, such as agents targeting tyrosine kinases or the CD20 molecule, combination therapies and improved supportive care, have changed the treatment landscape of B-ALL. METHOD AND RESULTS: Meanwhile, blinatumomab has been FDA-approved for MRD-positive or R/R B-ALL patients. Blinatumomab is a bispecific T cell engager containing the CD3 and CD19 that recognize domains redirecting cytotoxic T cells to lyse B cells. Promising outcomes, including long-term overall survival and improved MRD-negative response rates, have been reported in patients who received this drug. Adding blinatumomab to new ALL regimens seems promising for achieving better outcomes in poor prognosis B-ALL patients. Nevertheless, the neurotoxicity and cytokine release syndrome are the two major adverse events following the blinatumomab therapy. CONCLUSION: This review summarizes the function and effectiveness of blinatumomab in R/R and MRD positive B-ALL patients. Furthermore, blinatumomab's positive and negative aspects as a novel therapy for B-ALL patients have been briefly discussed.

Successful treatment of a pure red cell aplasia patient following ABO-mismatched hematopoietic stem cell transplantation from a sibling donor with multiple sclerosis.

Despite the importance of blood group compatibility in solid organ transplantation, the role of ABO antigens is less critical in hematopoietic stem cell transplantation (HSCT). However, ABO-mismatch HSCT can present specific conditions and challenges for the recipient. One of the possible consequences of ABO-mismatch HSCT is pure red cell aplasia (PRCA). Although there are different treatment strategies to manage PRCA, each may carry its own risk. Here, we report a patient who developed PRCA after ABO-mismatch allogeneic HSCT from her sibling with multiple sclerosis history. PRCA improved with tapering immunosuppressive agents. Although the patient developed manageable graft versus host disease (GVHD), she eventually recovered from both PRCA and GVHD.

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.

Prognostic Factors for the Long-Term Survival after Hematopoietic Stem Cell Transplantation in Patients with Hodgkin Lymphoma.

OBJECTIVES: This study investigated the possible prognostic factors for the long-term survival (Cure Rate) of Hodgkin Lymphoma patients who underwent HSCT. METHODS: This retrospective cohort study analyzed 116 Patients diagnosed with Hodgkin Lymphoma who received autologous hematopoietic stem cell transplantation (Auto-HSCT) between the years 2007 and 2014 and followed up until 2017. The information regarding patients' survival had been collected using phone calls, and their pre-transplant information was available in the archived documents. Prognostic effects were investigated using long-term survival models. RESULTS: Patients with obesity had five times higher odds of long-term survival (cure) than the others (P=0.06). Also, the recurrence experience after HSCT negatively impacted the curing potential by 78% (P=0.05). Also, with 32 years as the change point, patients younger than 32 had 76% fewer odds of surviving long-term (P=0.03), and Poor transfused stem cell dose of CD34+ (<0.16 × 106 cells/ml) reduced the odds of long-term survival by 92% (P=0.01). CONCLUSION: According to the statistical models used in this study, obesity can increase the curing potential of Hodgkin lymphoma after transplantation. Meanwhile, aging, poor transfused CD34+ cells, and recurrence after HSCT were associated with lower survival following HSCT.

Comparison of the Effects of Plasmapheresis, Hemoperfusion, and Convalescent Plasma Therapy on Inflammatory Factors in COVID-19 Patients.

Background: Since the emergence of coronavirus disease 2019 (COVID-19), the treatment protocols are continuously updated, based on the evidence gathered all around the world and reported to the World Health Organization. Like many other emerging infectious diseases, using convalescent plasma from those recovered from the disease was a preliminary treatment approach that showed partial effectiveness for severe COVID-19 patients. Besides, blood filtration strategies, such as hemoperfusion and plasmapheresis, are employed to lessen the load of inflammatory molecules. However, few studies compared their effects to conclude which treatment might be more efficacious for COVID-19 patients. We compared the effects of plasmapheresis or plasma exchange, convalescent plasma therapy, and hemoperfusion on O2 saturation and inflammatory factors in COVID-19 patients. Methods: In this retrospective study, 50 COVID-19 patients received standard treatments based the international guidelines. Patients were divided into 4 groups: hemoperfusion, plasmapheresis, plasma therapy, and control. The control group received only the standard treatments. The mortality rate, O2 saturation, and laboratory factors were compared between the 4 groups. Results: We found a significant decrease in the C-reactive protein level following hemoperfusion (32.75 ± 23.76 vs 13 ± 7.54 mg/dL; p = 0.032) but not plasmapheresis and plasma therapy. Besides, serum levels of lactate dehydrogenase (p = 0.327, 0.136, 0.550, for hemoperfusion, plasmapheresis, and plasma therapy, respectively) and other inflammatory molecules did not significantly change following treatments. There is also no significant difference in the mortality rate between the treatment groups (p = 0.353). Conclusion: It seems that hemoperfusion, plasmapheresis, and plasma therapy did not have considerable effects on decreasing the inflammation and mortality rate compared with standard treatment.

Post-hematopoietic stem cell transplantation relapse: Role of checkpoint inhibitors.

Background and Aims: Despite the revolutionary effects of hematopoietic stem cell transplantation (HSCT) in treating hematological malignancies, post-HSCT relapse is considered a critical concern of clinicians. Residual malignant cells employ many mechanisms to evade immune surveillance and survive to cause relapse after transplantation. One of the immune-frustrating mechanisms through which malignant cells can compromise the antitumor effects is misusing the self-limiting system of immune response by overexpressing inhibitory molecules to interact with the immune cells, leading them to so-called "exhausted" and ineffective. Introduction of these molecules, known as immune checkpoints, and blocking them was a prodigious step to decrease the relapses. Methods: Using keywords nivolumab, pembrolizumab, and ipilimumab, we investigated the literature to figure out the role of the immune checkpoints in the HSCT setting. Studies in which these agents were administrated for relapse after transplantation were reviewed. Factors such as the interval from the transplant to relapse, previous treatment history, adverse events, and the patients' outcome were extracted. Results: Here we provided a mini-review discussing the experiences of three immune checkpoints, including nivolumab, pembrolizumab, and ipilimumab, as well as the pros and cons of using their blockers in relapse control after HSCT. In conclusion, it seems that CI therapy seems effective for this population. Future investigations may provide detailed outlook of this curative options.

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.

The association of disease type, pre-transplant hemoglobin level and platelet count with transfusion requirement after autologous hematopoietic stem cell transplantation.

BACKGROUND: Autologous hematopoietic stem cell transplantation (auto-HSCT) has become an effective treatment for a wide range of hematologic and non-hematologic diseases. Patients undergoing HSCT might require multiple platelets and red blood cell (RBC) transfusions during aplasia phase until engraftment, which could profoundly affect patients' conditions. Identification of risk factors associated with blood product requirements could help in decreasing transfusion-related complications. We evaluated the association of disease type, pre-transplant hemoglobin level, and pre-transplant platelet count with RBC/platelet transfusion requirement after auto-HSCT. METHODS: In this retrospective study, 324 patients diagnosed with multiple myeloma (MM), Hodgkin disease (HD), and non-Hodgkin lymphoma (NHL) and underwent auto-HSCT were included. The associations of disease type, pre-transplant hemoglobin level, and platelet count with post-transplant packed cell and single-/random-donor platelet transfusions were evaluated. RESULTS: Our study results illustrated that the higher pre-transplant hemoglobin level significantly decreased the post-HSCT requirement for packed cell (IRR=0.81, [CI: 9.73-0.90], P=0.0001), while the pre-transplant platelet showed no significant relationship with platelet requirement after HSCT. HD was associated with increment in packed cell (IRR=2.04, [CI: 1.35-3.08], P=0.001) and single donor platelet (IRR=1.39, [CI: 1.09-1.78], P=0.008) requirement after transplant. The trends showed that a higher platelet level led to a lower need for platelet transfusion. CONCLUSION: Pre-transplant hemoglobin level could be valuable markers for predicting post-HSCT RBC requirements and might be beneficial for better management of transfusion requirements to minimize the transfusion-related complications. Patients with HD seem to be more prone to blood product requirements post-transplant.

In-depth summary over cytomegalovirus infection in allogeneic hematopoietic stem cell transplantation recipients.

In this study, we reviewed various aspects of cytomegalovirus infection, including pathophysiology, diagnosis methods, and antiviral treatments. Background: Infections continue to be a major reason of complications like high non-relapse morbidity and mortality rate after allogenic hematopoietic stem cell transplantation. Cytomegalovirus is the most common infection in immunocompromised patients or those with graft-versus-host disease. The Latent-cytomegalovirus disease could increase the risk of reactivation in allogenic hematopoietic stem cell transplantation patients and lead to profound adverse effects on transplantation outcomes. Cytomegalovirus-specific CD4 + and CD8 + T cells reconstitution is crucial for protection against the virus reactivation. Different prophylactic, pre-emptive, and therapeutic anti-viral drugs are available to prevent cytomegalovirus infection/reactivation and treat resistant infections. Conclusion: Although there has been introduced various CMV antiviral treatment strategies like antiviral drugs, Vaccination, passive immunotherapies and adoptive transfer of CMV-specific T cells, further clinical trials are required to approve current therapies.

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 effect of granulocyte colony-stimulating factor dose and administration interval after allogeneic hematopoietic cell transplantation on early engraftment of neutrophil and platelet.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is one of the treatments for hematologic malignancies. Numerous factors affect the HSCT outcome. The purpose of this study was to investigate the effect of post-HSCT administration of granulocyte colony-stimulating factor (post-G-CSF) on early neutrophil and platelet engraftment in allogeneic HSCT (allo-HSCT). MATERIAL & METHODS: The study was performed on 76 patients diagnosed with AML and ALL. All patients underwent allo-HSCT at Taleghani stem cell transplantation center, Tehran, Iran, from February 2016 to December 2018. Chemotherapy regimens based on patients' conditions were selected between myeloablative and reduced-intensity regimens. RESULTS: Statistical analysis revealed that the number of administered G-CSF units after HSCT was a time-dependent variable. Statistical analysis before day +11 reported that patients who received G-CSF <14 units had three times better early neutrophil engraftment than those with G-CSF ≥14 (CI 95%, AHR = 3.03, p:0.002). CD3+ cells count <318.5 × 106 /kg was associated with fast platelet engraftment (CI 95%, AHR 2.28, p:0.01). CONCLUSION: In this study, post-G-CSF stimulation was associated with early engraftment in a time- and dose-dependent manner. Administration of G-CSF beyond 14 units resulted in adverse effects on neutrophil early engraftment. It also appeared that with a reduction in CD3+ cell counts, the likelihood of GVHD decreases, and platelet engraftment occurs earlier. Further investigations in the future are required to determine the factors affecting the process of early engraftment.

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.

Pre-Transplantation Serum Parathyroid Hormone Influences the Number of Mobilized CD34+ Hematopoietic Stem Cells in Autologous Hematopoietic Stem Cell Transplantation.

BACKGROUND: Parathyroid hormone (PTH) is a calcium homeostasis regulator and can affect bone marrow niche. PTH leads to the bone marrow stem cell niche expansion as well as the induction of stem cell mobilization from the bone marrow into peripheral blood. In this study, we evaluated the association between pre- transplantation serum PTH levels and the number of circulating CD34+ cells along with the platelets/white blood cells (Plt/WBC) engraftment in patients who underwent autologous Hematopoietic Stem Cell Transplantation. METHODS: Subjects for the study were 100 patients who received autologous hematopoietic stem cell transplantation (auto-HSCT), retrospectively. Serum levels of PTH, calcium, phosphorus, and alkaline phosphatase were measured before mobilization. Their impacts were measured on the number of mobilized CD34+ hematopoietic stem cells, and Plt/WBC engraftment. RESULTS: High levels of serum PTH (> 63.10 pg/mL) was significantly associated with higher number of CD34+ cells in peripheral blood after granulocyte- colony stimulating factor (G-CSF)-induced mobilization (p= 0.079*). Serum calcium at low levels were associated with higher number of circulating CD34+ cells post mobilization. Pre- transplantation serum levels of phosphorus and alkaline phosphatase on CD34+ numbers were not statistically significant. Serum Plt/WBC engraftment was not improved in presence of high levels of serum PTH. CONCLUSION: We suggested that serum PTH levels before transplantation could be influential in raising the number of circulating CD34+ hematopoietic stem cell after mobilization.

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 apheresis content analysis in Allo-HSCT represents reliable influential factors on graft-versus-host disease and overall survival.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is an established treatment for hematologic malignancies. However the post-HSCT outcome can be affected by multiple pre-transplant, transplant, and post-transplant factors. The cellular content of graft could be possible factors influencing the graft-versus-host disease (GVHD) and overall survival (OS) as transplantation outcomes. PURPOSE: The aim of this study was to assess the impact of infused CD34+ cells, CD3+ cells, and MNC count on the patients' survival and incidence of graft-versus-host disease (GVHD). MATERIAL AND METHODS: We analyzed 87 patients with hematological malignancies who underwent allogeneic hematopoietic stem cell transplantation at the Taleghani Stem Cell Transplantation and Cell therapy center, Tehran, Iran from January 2016 to December 2018. Patients were conditioned with either myeloablative conditioning regimen or reduced-intensity regimen. RESULT: A CD34+ cell dose < 4.35 × 106/kg and CD3+ cell dose < 365 × 106/kg was associated with higher survival and lower acute and chronic GVHD incidence, although their association was not statistically significant. Moreover, there was a significant association between MNC count < 6.15 × 108/kg and acute GVHD incidence. CONCLUSION: Graft cell dose, lower than the cut-off level, could lead to better outcomes after allogeneic transplantation. However, this study showed that future investigations are required in a larger population of patients in order to determine the exact effect of allogeneic graft cell dose on transplantation outcome.