Novelty in improvement of CAR T cell-based immunotherapy with the aid of CRISPR system.

INTRODUCTION: Chimeric Antigen Receptor (CAR) T cells have tremendous potentials for cancer treatment; however, various challenges impede their universal use. These restrictions include the poor function of T cells in tumor microenvironments, the shortage of tumor-specific antigens and, finally, the high cost and time-consuming process, as well as the poor scalability of the method. Creative gene-editing tools have addressed each of these limitations and introduced next generation products for cell therapy. The clustered regularly interspaced short palindromic repeats-associated endonuclease 9 (CRISPR/Cas9) system has triggered a revolution in biology fields, as it has a great capacity for genetic manipulation. METHOD: In this review, we considered the latest development of CRISPR/Cas9 methods for the chimeric antigen receptor T cell (CAR T)-based immunotherapy. RESULTS: The ability of the CRISPR/Cas9 system to generate the universal CAR T cells and also potent T cells that are persistent against exhaustion and inhibition was explored. CONCLUSION: We explained CRISPR delivery methods, as well as addressing safety concerns related to the use of the CRISPR/Cas9 system and their potential solutions.

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.

Cytokine-Induced Memory-Like NK Cells: Emerging strategy for AML immunotherapy.

Acute myeloid leukemia (AML) is a heterogeneous disease developed from the malignant expansion of myeloid precursor cells in the bone marrow and peripheral blood. The implementation of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) has improved outcomes associated with AML, but relapse, along with suboptimal outcomes, is still a common scenario. In the past few years, exploring new therapeutic strategies to optimize treatment outcomes has occurred rapidly. In this regard, natural killer (NK) cell-based immunotherapy has attracted clinical interest due to its critical role in immunosurveillance and their capabilities to target AML blasts. NK cells are cytotoxic innate lymphoid cells that mediate anti-viral and anti-tumor responses by producing pro-inflammatory cytokines and directly inducing cytotoxicity. Although NK cells are well known as short-lived innate immune cells with non-specific responses that have limited their clinical applications, the discovery of cytokine-induced memory-like (CIML) NK cells could overcome these challenges. NK cells pre-activated with the cytokine combination IL-12/15/18 achieved a long-term life span with adaptive immunity characteristics, termed CIML-NK cells. Previous studies documented that using CIML-NK cells in cancer treatment is safe and results in promising outcomes. This review highlights the current application, challenges, and opportunities of CIML-NK cell-based therapy in AML.

Virus-Specific T Cells: Promising Adoptive T Cell Therapy Against Infectious Diseases Following Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is a life-saving therapy for various hematologic disorders. Due to the bone marrow suppression and its long recovery period, secondary infections, like cytomegalovirus (CMV), Epstein-Bar virus (EBV), and adenovirus (AdV), are the leading causes of morbidity and mortality in HSCT cases. Drug resistance to the antiviral pharmacotherapies makes researchers develop adoptive T cell therapies like virus-specific T cell therapy. These studies have faced major challenges such as finding the most effective T cell expansion methods, isolating the expected subtype, defining the functionality of the end-cell population, product quality control, and clinical complications after the injection. This review discusses the viral infections after HSCT, T cells characteristics during chronic viral infection, application of virus-specific T cells (VSTs) for refractory infections, standard methods for producing VSTs and their limitation, clinical experiences on VSTs, focusing on outcomes and side effects that can be helpful in decision-making for patients and further researches.

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.

Mesenchymal stromal cell-derived secretome-based therapy for neurodegenerative diseases: overview of clinical trials.

BACKGROUND: Over the past few years, mesenchymal stromal cells (MSCs) have attracted a great deal of scientific attention owing to their promising results in the treatment of incurable diseases. However, there are several concerns about their possible side effects after direct cell transplantation, including host immune response, time-consuming cell culture procedures, and the dependence of cell quality on the donor, which limit the application of MSCs in clinical trials. On the other hand, it is well accepted that the beneficial effects of MSCs are mediated by secretome rather than cell replacement. MSC secretome refers to a variety of bioactive molecules involved in different biological processes, specifically neuro-regeneration. MAIN BODY: Due to the limited ability of the central nervous system to compensate for neuronal loss and relieve disease progress, mesenchymal stem cell products may be used as a potential cure for central nervous system disorders. In the present study, the therapeutic effects of MSC secretome were reviewed and discussed the possible mechanisms in the three most prevalent central nervous system disorders, namely Alzheimer's disease, multiple sclerosis, and Parkinson's disease. The current work aimed to help discover new medicine for the mentioned complications. CONCLUSION: The use of MSC-derived secretomes in the treatment of the mentioned diseases has encouraging results, so it can be considered as a treatment option for which no treatment has been introduced so far.

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.

NK cell therapy in relapsed refractory multiple myeloma.

Recent advances in adoptive cell therapy have considerably changed the paradigm of cancer immunotherapy. Although current immunotherapies could cure many patients with multiple myeloma (MM), relapsed/refractory MM (RR/MM) is still challenging in some cases. Natural killer (NK) cells are innate immune cells that exert effective cytotoxic activity against malignant cells like myeloma cells. In addition to their antitumor properties, NK cells do not induce graft versus host disease following transplantation. Therefore, they provide a promising approach to treating RR/MM patients. Currently, attempts have been made to produce large-scale and good manufacturing practices (GMP) of NK cells. Ex vivo expanded/activated NK cells derived from the own patient or allogenic donors are potential options for NK cell therapy in MM. Besides, novel cell-based products such as NK cell lines and chimeric antigen receptor (CAR)-NK cells may provide an off-the-shelf source for NK cell therapy. Here, we summarized NK cell activity in the MM microenvironment and focused on different NK cell therapy methods for MM patients.

Cell-Based Therapy Approaches in Treatment of Non-obstructive Azoospermia.

The rate of infertility has globally increased in recent years for a variety of reasons. One of the main causes of infertility in men is azoospermia that is defined by the absence of sperm in the ejaculate and classified into two categories: obstructive azoospermia and non-obstructive azoospermia. In non-obstructive azoospermia, genital ducts are not obstructed, but the testicles do not produce sperm at all, due to various reasons. Non-obstructive azoospermia in most cases has no therapeutic options other than assisted reproductive techniques, which in most cases require sperm donors. Here we discuss cell-based therapy approaches to restore fertility in men with non-obstructive azoospermia including cell-based therapies of non-obstructive azoospermia using regenerative medicine and cell-based therapies of non-obstructive azoospermia by paracrine and anti-inflammatory pathway, technical and ethical challenges for using different cell sources and alternative options will be described, and then the more effectual approaches will be mentioned as future trends.

Treatment of insulin-dependent diabetes by hematopoietic stem cell transplantation.

Type 1 diabetes (T1D) is an autoimmune disease resulting from the demolition of ß-cells that are responsible for producing insulin in the pancreas. Treatment with insulin (lifelong applying) and islet transplantation (in rare cases and severe diseases), are standards of care for T1D. Pancreas or islet transplantation have some limitations, such as lack of sufficient donors and longtime immune suppression for preventing allograft rejection. Recent studies demonstrate that autologous hematopoietic stem cells (HSC) can regenerate immune tolerance against auto-antigens. Taking advantage of this feature, autologous HSC transplantation (auto-HSCT) is likely the only treatment for T1D that is associated with lasting and complete remission. None of the other evaluated immunotherapies worldwide had the clinical efficacy of auto-HSCT. Therapy with auto-HSCT is insulin-independent rather than reducing insulin needs or delaying loss of insulin production. This review provided the latest findings in auto-HSCT for treatment of T1D.

Potential and challenges of placenta-derived decidua stromal cell therapy in inflammation-associated disorders.

Decidual stromal cells (DSCs) isolated from maternal part of placenta, like mesenchymal stromal cells (MSCs), are able to inhibit alloreactivity in-vitro but in a superior way which makes them an attractive alternative for anti-inflammatory therapies. In alloreactivity, when a strong immune response is developed against alloantigens, DSCs develop an anti-inflammatory environment, both through cell-to-cell contact and soluble factors, to prevent the adverse effects of alloantigens. In alloreactivity-associated inflammation, proinflammatory cytokines can be released and then involved in the up-regulation of inflammatory reactions which is one of the main causes of inflammatory related disorders. According to the preclinical and clinical studies, DSCs could be promising alternatives for the treatment of inflammatory-related diseases for which no definitive and successful treatment has been found yet. Here we first present the DSCs functions in creating the anti-inflammatory environment, their immunomodulatory effects, and their advantages over MSCs. Then, preclinical and clinical studies using DSCs for treatment of inflammatory disease including: graft-versus-host-disease (GVHD) after allogeneic hematopoi-etic stem cell transplantation (Allo-HSCT), COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) and in particular, Infertility-related disorders, are presented. Finally, the challenges of using DSCs in clinical settings will be described.

Decidual stromal cell therapy for generalized lymphadenopathy as a special clinical manifestation of COVID-19 infection: A case report.

We are going through the greatest global health crisis of the last decades, the coronavirus disease 2019 (COVID-19) pandemic. It may cause morbidity and mortality in some cases, and there is no therapeutic approach with reproducible and favorable outcomes. As clinical manifestations differ from patient to patient, any report regarding clinical symptoms has been beneficial for early detection and treatment. Due to the immunomodulatory effect of mesenchymal stem cells (MSCs), MSCs-based therapy has been approved to be one of the therapeutic strategies for COVID-19 management. For the first time in the literature, we reported generalized lymphadenopathy with fever and no sign of respiratory distress in a 16-year-old patient with confirmed COVID-19 infection as the main clinical signs. We also introduce decidual stromal cells as a potential immunomodulatory treatment for COVID-19-infected patients.

The Impact of Different Cell Culture Mediums on CD8+ T Cells Expansion: A Bioinformatics Study.

Objective: Different Cell Culture medias can affect the expansion of T cells. The aim of this study is to assess signaling pathways, protein interactions and genes in T cells cultured in different common T cell expansion medias to select the best candidate. Materials and Methods: In this in silico observational study, with the use of bioinformatics analysis and the use of enrichment databases, gene expression profiles were investigated using microarray analysis. Results: The results of this study were the joint selection of 26 upregulated genes and 59 downregulated genes that were involved in SREBP control of lipid synthesis, co-stimulatory signal during T-cell activation mitosis and chromosome dynamics, telomeres, telomerase, and cellular aging signal pathways. Conclusion: Using bioinformatics analyzes, integrated and regular genes were selected as common genes CD80, LST1, ATM and ITM2B 4-1BBL, Akt inhibitor, interleukin 7 and 15 expansion media.

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.

Highlighting the interaction between immunomodulatory properties of mesenchymal stem cells and signaling pathways contribute to Graft Versus Host Disease management.

Background Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) has been increasingly used as a therapeutic approach for hematological malignancies. Several potential strategies have been developed for treating or preventing allo-HSCT complications, specifically graft-versus-host disease (GVHD). GVHD could significantly affect the morbidity and mortality of patients after allo-HSCT. Curative treatment and prophylaxis regimens for GVHD could reduce GVHD incidence and improve survival rate. Among these therapeutic strategies, mesenchymal stem cell (MSCs) mediated immunomodulation has been explored widely in clinical trials. MSCs immunomodulation ability in GVHD correlates with the interactions of MSCs with innate and adaptive immune cells. However, signaling pathways responsible for MSCs' impact on GVHD regulation, like JAK/STAT, NOTCH, MAPK/ERK, and NFκß signaling pathways, have not been clearly described yet. This review aims to illuminate the effect of MSCs-mediated immunomodulation in GVHD management after allo-HSCT representing the role of MSCs therapy on signaling pathways in GVHD. Conclusion MSCs could potentially modulate immune responses, prevent GVHD, and improve survival after allo-HSCT. Previous studies have investigated different signaling pathways' contributions to MSCs immunoregulatory ability. Accordingly, targeting signaling pathways components involved in MSCs related GVHD regulation is proven to be beneficial.

Association Between Human Leukocyte Antigens and Graft-Versus-Host Disease Occurrence in Allogeneic Hematopoietic Stem Cell Transplantation - A 10-Year Experience on Iranian Patients.

BACKGROUND: Human leukocyte antigen (HLA) molecules mediate critical roles in determining responsiveness or non-responsiveness of the immune system, especially in transplantation. Some studies have shown a possible association between certain HLA alleles and some allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes such as acute/chronic graft-versus-host disease (aGVHD/cGVHD) and overall survival (OS). In the current study, we investigated any possible association of HLA subclasses and acute/chronic GVHD occurrence as well as OS in patients receiving HLA-matched sibling allo-HSCT. METHODS: We retrospectively evaluated the association of various HLA alleles with the incidence of aGVHD, cGVHD, and OS of 162 patients who received allo-HSCT from HLA-matched sibling between 2009-2018 at Taleghani hospital in Tehran. RESULTS: We found that the incidence of aGVHD grades II-IV was higher among patients who had HLA-B*07 (P=0.031) and HLA-DRB1*07 (P=0.052). The presence of HLA-A*01 was associated with 4.5-fold greater odds of incidence in the extensive-type of cGVHD (P=0.009). Furthermore, HLA-A*03 (P=0.089), HLA-B*13(P=0.013), HLA-B*40 (P=0.042), HLA-DRB1*02 (P=0.074), and HLA-DRB1*04 (P=0.039) were associated with a lower rate of OS. CONCLUSION: This study suggests that certain HLA alleles might influence the incidence and severity of acute or chronic GVHD in the context of HLA-matched sibling allo-HSCT. In addition, some specific HLA alleles help predict OS in allo-HSCT recipients. These results might be helpful in estimating the incidence of aGVHD, cGVHD, and OS as well as designing personalized therapy.

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.

Assessment of the Effect of Infliximab on Immunomodulation Properties of Mesenchymal Stem Cells In Vitro.

Purpose: Mesenchymal stem cells (MSCs) have immunomodulatory traits making them a promising choice in the treatment of inflammatory diseases such as graft-versus-host disease (GVHD). Tumor necrosis factor-alpha (TNFα) is a major player of inflammatory disease which is blocked by infliximab to reduce the inflammation. The present study aims to assess the infliximab effects on the anti-inflammatory properties of MSCs. Methods: In this study, bone marrow mesenchymal stem cells (BMMSCs) were co-cultured with peripheral blood mononuclear cells (PBMCs) of GVHD patients in the presence of 10, 20 and 30 µg/mL of infliximab for 48 and 72 hours. The mRNA expression of indoleamine-2,3- dioxygenase (IDO) and inducible nitric oxide synthase (iNOS), as well as the secreted amount of prostaglandin E2 (PGE2) in the culture supernatant, were examined. Results: The results of this study show that the expression of IDO and iNOS genes, as well as the secretion amount of PGE2 in co-cultured groups raised dramatically, compared to the culture of BMMSCs or PBMCs alone. In co-culture groups containing infliximab, the expression of IDO and iNOS and also the amount of released PGE2 was significantly decreased compared to the control group without infliximab. However, no difference was found in the expression of assayed factors between 48 and 72 hours of treatments. Conclusion: As an anti-TNFα agent, infliximab can decrease the inflammation in the microenvironment of MSCs, which might mitigate the immunomodulatory effects of MSCs. These effects of anti-inflammatory agents on the immunomodulatory capacity of MSCs should be considered in MSC therapy.

The rare Hematological disorder; A man with Hemophagocytic Lymphohistiocytosis (HLH).

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare disease with different causes. HLH has been categorized into two sub-groups; primary HLH which is associated with some gene mutations and secondary HLH that is developed by various causes, such as autoimmune disease, infections, and malignancies. However, the symptoms of both groups are identical and if left untreated, it will result in death. CASE PRESENTATION: In this study, we reported a 39 years old man had symptoms such as fever, weakness and chill for a month period of time. Firstly, due to pancytopenia in peripheral blood findings and clinical manifestations, he had been diagnosed with myelodysplastic syndrome (MDS) with an excess blast but the elevated liver enzymes and bilirubin were not consistent with this diagnosis. Hence, we recommended more investigation such as CT scan, bone marrow aspiration and bone marrow biopsy with immunohistochemistry tests. Finally, we found macrophages and histiocyte in bone marrow biopsy smear with Wright-Giemsa staining that engulfed the cells such as platelets and lymphocytes, so HLH syndrome was confirmed and treatment program with latest approved protocols started for the patient. CONCLUSION: HLH syndrome is a life-threatening disease that can be saved if timely diagnosed. Therefore, more consideration of all the laboratory findings and clinical signs of the patient can help to diagnose the disease more accurately. Also, we did a review of its pathophysiology, symptoms and therapeutic treatments.

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.