Donor Availability Research Articles

Identification of high-oleic peanut chemical mutants and functional analysis of mutated FAD2B gene

AbstractIt is generally accepted that high-oleic crops have at least 70% oleate. As compared to their normal-oleic counterparts, oil and food products made from high-oleic peanut have better keeping quality and are much healthier. Therefore, high-oleic peanut is well recognized by processors and consumers. However, owing to the limited availability of high-oleic donors, most present-day high-oleic peanut varietal releases merely have F435 type FAD2 mutations. Through screening of a mutagenized peanut population of 15L46, a high-yielding peanut line with desirable elliptical oblong large seeds, using near infrared model for predicting oleate content in individual single seeds, high-oleic peanut mutants were identified. Sequencing FAD2A and FAD2B of the mutants along with the wild type revealed that these mutants possessed G448A FAD2A (F435 type FAD2A mutation) and G558A FAD2B (non-F435 type FAD2B mutation). Expression of the wild and mutated type FAD2B in yeast verified that the functional mutation contributed to the high-oleic phenotype in these mutants. The mutants provided additional high-oleic donors to peanut quality improvement.

Real-World Experience of Cryopreserved Allogeneic Hematopoietic Grafts during the COVID-19 Pandemic: A Single-Center Report

In response to the widespread COVID-19 pandemic, cryopreservation of allogeneic donor apheresis products was implemented to mitigate the challenges of donor availability and product transport. Although logistically beneficial, the impact of cryopreservation on clinical outcomes and graft composition remains unclear. In this study, we compared outcomes and graft composition with cryopreserved versus fresh allografts in the setting of allogeneic hematopoietic cell transplantation (allo-HCT). We retrospectively analyzed the clinical outcomes of 30 consecutive patients who received cryopreserved allografts between March and August 2020 and 60 consecutive patients who received fresh allografts before the COVID-19 pandemic. Primary endpoints were hematopoietic engraftment and graft failure (GF), and secondary outcomes were overall survival (OS), relapse-free survival (RFS) and nonrelapse mortality (NRM). In addition, extended immunophenotype analysis was performed on cryopreserved and prospectively collected fresh apheresis samples. Compared with recipients of fresh allografts, both neutrophil and platelet recovery were delayed in recipients of cryopreserved reduced-intensity conditioning (RIC) allo-HCT, with a median time to engraftment of 24 days versus 18 days (P = .01) for neutrophils and 27 days versus 18 days (P = .069) for platelets. We observed primary GF in 4 of 30 patients in the cryopreserved cohort (13.3%) versus only 1 of 60 patients (1.7 %) in the fresh cohort (P = .03). Cryopreserved RIC allo-HCT was associated with significantly lower median total, myeloid, and T cell donor chimerism at 1 month. OS and RFS were inferior for cryopreserved graft recipients (hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.00 to 4.67) and HR, 1.90; 95% CI, 0.95 to 3.79, respectively. Using an extended immunophenotype analysis, we compared 14 samples from the cryopreserved cohort to 6 prospectively collected fresh apheresis donor samples. These analyses showed both a decrease in total cell viability and a significantly reduced absolute number of natural killer cells (CD3−CD56+) in the cryopreserved apheresis samples. In this single-institution study, we found delayed engraftment and a trend toward clinical inferiority of cryopreserved allografts compared with fresh allografts. Further evaluation of the use of cryopreserved allografts and their impact on clinical and laboratory outcomes is warranted.

Preemptive Immunotherapy for Minimal Residual Disease in Patients With t(8;21) Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

In patients with t(8;21) acute myeloid leukemia (AML), recurrent minimal residual disease (MRD) measured by RUNX1-RUNX1T1 transcript levels can predict relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to compare the efficacy of preemptive interferon (IFN)-α therapy and donor lymphocyte infusion (DLI) in patients with t(8;21) AML following allo-HSCT. We also evaluated the appropriate method for patients with different levels of RUNX1-RUNX1T1 transcripts. In this retrospective study, consecutive patients who had high-risk t(8;21) AML and received allo-HSCT were enrolled. The inclusion criteria were as follows: (1) age ≤65 years; (2) regained MRD positive following allo-HSCT. MRD positive was defined as the loss of a ≥4.5-log reduction and/or <4.5-log reduction in the RUNX1-RUNX1T1 transcripts, and high-level, intermediate-level, and low-level MRDs were, respectively, defined as <2.5-log, 2.5−3.5-log, and 3.5−4.5-log reductions in the transcripts compared with the pretreatment baseline level. Patients with positive RUNX1-RUNX1T1 could receive preemptive IFN-α therapy or DLI, which was primarily based on donor availability and the intentions of physicians and patients. The patients received recombinant human IFN-α-2b therapy by subcutaneous injection twice a week every 4 weeks. IFN-α therapy was scheduled for six cycles or until the RUNX1-RUNX1T1 transcripts were negative for at least two consecutive tests. The rates of MRD turning negative for patients with low-level, intermediate-level, and high-level RUNX1-RUNX1T1 receiving IFN-α were 87.5%, 58.1%, and 22.2%, respectively; meanwhile, for patients with intermediate-level and high-level RUNX1-RUNX1T1 receiving DLI, the rates were 50.0% and 14.3%, respectively. For patients with low-level and intermediate-level RUNX1-RUNX1T1, the probability of overall survival at 2 years was higher in the IFN-α group than in the DLI group (87.6% vs. 55.6%; p = 0.003). For patients with high levels of RUNX1-RUNX1T1, the probability of overall survival was comparable between the IFN-α and DLI groups (53.3% vs. 83.3%; p = 0.780). Therefore, patients with low-level and intermediate-level RUNX1-RUNX1T1 could benefit more from preemptive IFN-α therapy compared with DLI. Clinical outcomes were comparable between preemptive IFN-α therapy and DLI in patients with high-level RUNX1-RUNX1T1; however, they should be further improved.

Early Phenotype Programming in Birds by Temperature and Nutrition: A Mini-Review

Early development is a critical period during which environmental influences can have a significant impact on the health, welfare, robustness and performance of livestock. In oviparous vertebrates, such as birds, embryonic development takes place entirely in the egg. This allows the effects of environmental cues to be studied directly on the developing embryo. Interestingly, beneficial effects have been identified in several studies, leading to innovative procedures to improve the phenotype of the animals in the long term. In this review, we discuss the effects of early temperature and dietary programming strategies that both show promising results, as well as their potential transgenerational effects. The timing, duration and intensity of these procedures are critical to ensure that they produce beneficial effects without affecting animal survival or final product quality. For example, cyclic increases in egg incubation temperature have been shown to improve temperature tolerance and promote muscular growth in chickens or fatty liver production in mule ducks. In ovo feeding has also been successfully used to enhance digestive tract maturation, optimize chick development and growth, and thus obtain higher quality chicks. In addition, changes in the nutritional availability of methyl donors, for example, was shown to influence offspring phenotype. The molecular mechanisms behind early phenotype programming are still under investigation and are probably epigenetic in nature as shown by recent work in chickens.

FEATURES AND STRATEGIES FOR SCAFFOLD DESIGN AND PRODUCTION FOR TISSUE ENGINEERING

Failure or loss of human tissues and organs due to illness or injury requires the partial or even total transplantation. Although transplantation is a successful intervention, donor availability and immune rejections represent still the main drawbacks. In addition, the fast and proper recovery of the patient is nowadays more than necessary to prevent infection, chronic inflammation, and other complications during the tissue/organ healing process. There is still a tremendous interest of alternatives to transplantation, such as scaffold-based tissue engineering, that may contribute to practical outcomes for the worldwide health concern related to severe tissue injuries. Herein, we explore the features, benefits and scaffold designs applied for biotechnological sciences, particularly for tissue engineering. The great potential to transform biocompatible polymers in three-dimensional matrix, assimilating the extracellular matrix (ECM), makes them attractive for cells adhesion and proliferation. On the basic of relevant results recently reported in the literature, along with the pioneering works, we discuss specific issues and challenges such as matrix-cell interactions, strategies to design scaffolds with homogeneous nano/microscales using different techniques, e.g., hydrogels, electrospinning, and rotary jet spinning, as well as the combination of some of these techniques.

Lung transplantation from past to future

Lung transplantation is performed on patients with terminal lung diseases and is generally done in two scenarios: when a patient with terminal stage lung disease is predicted to have 50% or less chances of survival in the next 2–3 years and/or advancement of lung disease to such a stage that clear survival advantage of lung transplantation is evident. It was first done in humans in 1963 by Dr James Hardy. Proper timing of transplant is important. It should be neither too late nor too early. Listing of patients for lung transplantation was initially a problem but subsequently with the introduction of lung allocation scores (LAS) by the United Network for Organ Sharing in 2005, the waiting list mortality has decreased significantly. LAS is a concept to prioritize organ allocation based on the expected survival advantage of transplantation. The LAS is aimed to pick up the best-suited candidates for transplant and to decrease waiting list mortality. The decision to do single or double lung transplantation is multifactorial. It depends on transplant indications, recipient factors, and donor availability. As with any other transplant, lung transplantation needs posttransplant immunosuppression. Postlung transplant immunosuppression generally consists of a regimen consisting of calcineurin inhibitors, purine synthesis antagonists, and prednisolone. Immunosuppression and drug toxicity are the main cause of early complications. Complications vary with time postoperatively. Primary graft dysfunction is the major concern in the first month after transplant. Acute rejection infections predominate in the subsequent posttransplant period. Neoplasia and chronic lung allograft dysfunction predominate after the first year. The initial attempts resulted in a poor outcome but is now routinely performed as the results have been much more promising in this era due to advances in surgical techniques and immunosuppression regimens. Lung transplantation no doubt offers better survival but is still unfortunately only 50% at 5 years. There is somewhat unawareness among the clinicians about lung transplantation. Our primary aim of this review is to aware young clinicians about the possible role of lung transplantation in terminal lung diseases. Thus, keeping in mind our primary aim, this review provides an overview of lung transplantation in terms of historical background, candidate selection criteria, concept of LAS, methods of bridging to transplantation, single versus bilateral transplantation, post-lung immunosuppression, outcome, and complications.

Improving the Availability of Unrelated Stem Cell Donors: Evidence from a Major Donor Registry

Improving the Availability of Unrelated Stem Cell Donors: Evidence from a Major Donor Registry

Deceased donor renal transplant outcome in a south Indian tertiary care hospital with zonal allocation model - An observational study

Background: With the rising incidence of diabetes and hypertension, the prevalence of end-stage renal disease has increased greatly so as the need for renal replacement therapy. Availability of suitable living-related donors is a major problem which increases the demand for deceased donor renal transplantation (DDRT), making it a lifeline for the patients on dialysis without any living donors. Methodology: This is a retrospective analysis of 118 DDRT done between 2012 and 2020, in a private quaternary care hospital in a south Indian state. All patients received basiliximab induction, with maintenance immunosuppression using steroids, mycophenolate mofetil (MMF) or mycophenolate sodium, and tacrolimus. Results: In our study, we report unadjusted graft survival of 93.2% and 81.3%, patient survival of 94.9% and 83.1% at the end of 1 and 5 years, respectively. The recipients with age < 60 years had 5 years graft survival of 87%. The study group consisted of 15.25% of the patients with panel reactive antibody (PRA) positive and 10.16% of them with donor-specific antibody (DSA) during renal transplantation, and there was only one allograft loss in this subset of the patients. Conclusion: This study confirms that human leukocyte antigen matching is not very important with the current immunosuppressive protocol using tacrolimus and MMF. Early initiations of tacrolimus do not increase the incidence of delayed graft function. We report 91.6% graft survival in the DSA-positive group, with basiliximab induction and desensitization protocol.

Improving the Availability of Unrelated Stem Cell Donors: Evidence from a Major Donor Registry

Improving the Availability of Unrelated Stem Cell Donors: Evidence from a Major Donor Registry

Improving the Availability of Unrelated Stem Cell Donors: Evidence from a Major Donor Registry

Improving the Availability of Unrelated Stem Cell Donors: Evidence from a Major Donor Registry

Human Umbilical Cord Blood Therapy for Diabetes Mellitus : A Review

Stem cell therapy for patients with diabetes mellitus is receiving great attention among scientists and clinicians. Although bone marrow is considered one of the rich sources of stem cells, its limited availability of donors precludes its use for all the suitable patients. Human umbilical cord blood mononuclear cells or its-derived mesenchymal cells are being increasingly used as an alternative source of stem cells for cell-based therapy for malignant and nonmalignant diseases. Human umbilical cord blood cells have low potential for graft-versus-host disease and tumorigenicity. Also, no immunosuppression is required. Experimental evidence has shown that human umbilical cord blood -derived stem cells can differentiate into insulin-secreting β-cells. Transplantation of Human umbilical cord blood cells has been shown to improve blood glucose levels, and ameliorate kidney as well as neuropathic complications in diabetic animal models. Although the first use of autologous Human umbilical cord blood transfusion in type 1 diabetic children had a short-term beneficial effect in reducing the daily requirement of insulin dose and the maintenance of near normoglycemia, subsequent studies have failed to show this beneficial effect. In this review, we will provide both experimental and clinical evidence in favor and against the beneficial effect of human umbilical cord blood cells and cord blood-derived mesenchymal cells in the management of diabetes mellitus.

In-silico Study for African Plants with Possible Beta-Cell Regeneration Effect through Inhibition of DYRK1A

Background: The continuous destruction of normal insulin-producing pancreatic beta cells is a contributing factor in all common forms of diabetes, due to insufficient production of insulin, especially in type 1 diabetes. There are attempts to betacells transplantation, but the cost and availability of donors pose a great challenge to the process. Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A plays a crucial role in beta-cells destruction. Aims: Our research targets to identify plants for that can be utilized possible alternative approach of beta-cell replacement through a pharmacologically induced regeneration of new beta cells in-silico. Methods and Material: The 3D structure Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A and 6511 phytochemicals were obtained from Protein Databank and African Natural Products Database respectively. They were appropriately prepared for molecular docking simulations. Molecular docking simulations were implemented, after validation of docking protocols, in AutoDock-Vina®, using virtual screening scripts. Phytocompounds with good binding affinities for Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A were selected as frontrunners. The compounds were screened for toxicity and Lipinski’s rule confirmation using Datawarrior and then kinase inhibitory bioactivity prediction using Molinspiration. Results: Twelve phytocompounds were found to be predictably highly active in-silico against Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A, druglike based on Lipinski’s rule, non-mutagenic, non-tumorigenic, no reproductive effect and non-irritant, with high bioactivity prediction. Conclusions: In-silico active phytocompounds against Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A with their plant sources and physicochemical parameters were identified. Further studies will be carried out in-vitro and in-vivo in to validate the results of this study using plants containing the identified phytocompounds.

In vivo evaluation of bioprinted cardiac patches composed of cardiac-specific extracellular matrix and progenitor cells in a model of pediatric heart failure.

Pediatric patients with congenital heart defects (CHD) often present with heart failure from increased load on the right ventricle (RV) due to both surgical methods to treat CHD and the disease itself. Patients with RV failure often require transplantation, which is limited due to lack of donor availability and rejection. Previous studies investigating the development and in vitro assessment of a bioprinted cardiac patch composed of cardiac extracellular matrix (cECM) and human c-kit + progenitor cells (hCPCs) showed that the construct has promise in treating cardiac dysfunction. The current study investigates in vivo cardiac outcomes of patch implantation in a rat model of RV failure. Patch parameters including cECM-inclusion and hCPC-inclusion are investigated. Assessments include hCPC retention, RV function, and tissue remodeling (vascularization, hypertrophy, and fibrosis). Animal model evaluation shows that both cell-free and neonatal hCPC-laden cECM-gelatin methacrylate (GelMA) patches improve RV function and tissue remodeling compared to other patch groups and controls. Inclusion of cECM is the most influential parameter driving therapeutic improvements, with or without cell inclusion. This study paves the way for clinical translation in treating pediatric heart failure using bioprinted GelMA-cECM and hCPC-GelMA-cECM patches.

A new flow cytometry assay identifies recipient IgG subtype antibodies binding donor cells: increasing donor availability for highly sensitised patients

ObjectivesThere are four immunoglobulin (IgG) subtypes that have varying complement‐activating ability: strong (IgG3 and IgG1) and weak (IgG2 and IgG4). The standard flow cytometric crossmatch (FCM) assay does not distinguish between the various subtypes of the IgG molecule. This study outlines the development and use of a novel cell‐based IgG subtype‐specific FCM assay that is able to detect the presence of and quantitate the IgG subtypes bound to donor cells.MethodsA six‐colour lyophilised reagent was designed that specifically detects the four IgG subtypes, as well as distinguishes between T cells and B cells in the lymphocyte population. To test the efficacy of this reagent, a retrospective evaluation of a group of highly sensitised patients awaiting heart and kidney transplant was carried out, who, because of positive standard FCM results, had been deemed incompatible with numerous prior potential donors.ResultsObservations in this study demonstrate that the positive standard FCM results were mainly because of the presence of noncomplement‐activating IgG2 or IgG4 antibodies. The results were supported by the absence of C3d‐binding donor‐specific antibodies (DSA) and a negative complement‐dependent cytotoxicity crossmatch (CDC).ConclusionPreliminary data presented in this study demonstrate the reliability of the novel IgG subtype assay to detect the presence of pretransplant, complement‐activating antibodies bound to donor cells. The knowledge gained from the IgG subtype assay and the C3d‐binding specificities of DSAs provides improved identification of donor suitability in pretransplant patients, potentially increasing the number of transplants.

The Evolving Role of Allogeneic Stem Cell Transplant in the Era of Molecularly Targeted Agents.

Allogeneic stem cell transplantation (allo-SCT) is an increasingly important treatment strategy in fit adults with acute myeloid leukemia (AML). Increased donor availability and a steady reduction in transplant-related mortality (TRM) over the last 2 decades have transformed access to the curative potential of allo-SCT. The identification of patients with AML in first complete remission who will benefit from allo-SCT requires a dynamic assessment of the risk of disease relapse and TRM. Increased accuracy in predicting both relapse risk and transplant toxicity has allowed recommendations for allo-SCT to become increasingly personalized. Notwithstanding its now central position in the treatment algorithm of patients with AML, there, however, has been little progress in reducing the main cause of transplant failure, which remains disease relapse. Novel molecularly targeted therapies have the potential to augment the curative potential of nontransplant therapies, and this may influence the proportion of newly diagnosed fit patients deemed to be allomandatory. At the same time, the ability of such therapies to improve transplant outcomes, either by reducing TRM or the risk of relapse, has the potential to further embed allo-SCT as a key therapeutic modality in AML.

Turn around time in matched unrelated donor search workup national versus international registries: Retrospective study

Background: Timeline is a key factor for hematopoietic stem cell transplant (HSCT) recipient. HSCT by matched unrelated donor (MUD) is a standard definitive therapeutic approach for many hematological disorders which are not amenable to chemotherapy and other conventional treatment. Aims and Objectives: The aim of the present study was to compare the turnaround time (TAT) involved in completion of MUD HSCT workup from an Indian registry (Genebandhu) with international registries. Materials and Methods: On receipt of pre-transplant matching request through a transplant physician, patient's human leukocyte antigen (HLA) type was entered in both Genebandhu and World Marrow Donor Association search tool for initiating a “search.” The software gave the descending order of the best possible matches by performing computational analysis. The search result was considered a “match” when potential 10/10 HLA match was found. The average TAT was calculated in the middle of search request and HLA confirmatory typing (CT) and infectious disease marker (IDM). Further, TAT was also determined between the infusion of harvested stem cell product and CT and IDM. At last, the total time engaged in completion of each MUD HSCT workup was determined and compared in national versus international registries. Results: The average TAT involved in between search request and CT and IDM was 71 days in case of global registry and 67 days in case of Genebandhu. Similarly, the average TAT involved between infusion of harvested cell product and CT and IDM testing in case of donor identified in global stem cell registry was 65 days whereas 45 days in case of Genebandhu. At last, the average time associated with the finishing of a MUD workup was 136 days in case of global registry, whereas 112 days in the case of Genebandhu at P ≤ 0.05 with a 95% confidence interval. Conclusion: To conclude, the average TAT obtained through this study clearly demonstrates the advantages in terms of donor availability for MUD HSCT through the national registry.

Development of a novel and synthetic HematoMiR technology that broadly modulates quiescence of stem cells and enhances HSC expansion.

Hematopoietic stem cell (HSCs) transplantation is the primary therapeutic modality used to treat hematopoietic disorders. It centers on the capability of a small quantity of HSCs to repopulate whole blood lineages. Along with limited availability of suitable donors, the need for sufficient number of donor HSCs is still challenging in clinical relevance. This has been addressed by ex vivo HSC expansion albeit with partial success, and thus development of an alternative strategy that could improve HSC expansion is required. To that end, we aimed to build HematoMiR, an oligo-based technology that broadly targets HSC quiescence factors. Here, we show that HematoMiRs and their combinations targeting over 50 factors involved in HSC quiescence could induce robust ex vivo murine and human HSC expansion. In particular, HematoMiR-5 treatment enhanced cell cycle through down-regulation of negative cell cycle regulators in HSCs. HematoMiR-5 treated HSPCs had reduced DNA damage during the course of ex vivo expansion. Moreover, HematoMiR-5 treatment led to sustained HSC self-renewal ability and a low apoptosis rate. In addition, HematoMiR-5 expanded HSCs demonstrated successful engraftment and repopulation capacity in the recipient animals. Furthermore, combinatorial treatments of HematoMiR-2 and 5 allowed vigorous ex vivo HSC expansion. These findings demonstrate that novel and synthetic HematoMiR technology is feasible for HSC ex vivo expansion through the sequence-dependent modulation of numerous HSC quiescence modulators.

Cadaveric Stem Cells: Their Research Potential and Limitations.

In the era of growing interest in stem cells, the availability of donors for transplantation has become a problem. The isolation of embryonic and fetal cells raises ethical controversies, and the number of adult donors is deficient. Stem cells isolated from deceased donors, known as cadaveric stem cells (CaSCs), may alleviate this problem. So far, it was possible to isolate from deceased donors mesenchymal stem cells (MSCs), adipose delivered stem cells (ADSCs), neural stem cells (NSCs), retinal progenitor cells (RPCs), induced pluripotent stem cells (iPSCs), and hematopoietic stem cells (HSCs). Recent studies have shown that it is possible to collect and use CaSCs from cadavers, even these with an extended postmortem interval (PMI) provided proper storage conditions (like cadaver heparinization or liquid nitrogen storage) are maintained. The presented review summarizes the latest research on CaSCs and their current therapeutic applications. It describes the developments in thanatotranscriptome and scaffolding for cadaver cells, summarizes their potential applications in regenerative medicine, and lists their limitations, such as donor’s unknown medical condition in criminal cases, limited differentiation potential, higher risk of carcinogenesis, or changing DNA quality. Finally, the review underlines the need to develop procedures determining the safe CaSCs harvesting and use.

Immunotherapy as a Turning Point in the Treatment of Acute Myeloid Leukemia

Simple SummaryDespite recent progress achieved in the management of acute myeloid leukemia (AML), it remains a life-threatening disease with a poor prognosis, particularly in the elderly, having an average 5-year survival of approximately 28%. However, recent evidence suggests that immunotherapy can provide the background for developing personalized targeted therapy to improve the clinical course of AML patients. Our review aimed to assess the immunotherapy effectiveness in AML by discussing the impact of monoclonal antibodies, immune checkpoint inhibitors, chimeric antigen receptor T cells, and vaccines in AML preclinical and clinical studies.Acute myeloid leukemia (AML) is a malignant disease of hematopoietic precursors at the earliest stage of maturation, resulting in a clonalproliferation of myoblasts replacing normal hematopoiesis. AML represents one of the most common types of leukemia, mostly affecting elderly patients. To date, standard chemotherapy protocols are only effective in patients at low risk of relapse and therapy-related mortality. The average 5-year overall survival (OS) is approximately 28%. Allogeneic hematopoietic stem cell transplantation (HSCT) improves prognosis but is limited by donor availability, a relatively young age of patients, and absence of significant comorbidities. Moreover, it is associated with significant morbidity and mortality. However, increasing understanding of AML immunobiology is leading to the development of innovative therapeutic strategies. Immunotherapy is considered an attractive strategy for controlling and eliminating the disease. It can be a real breakthrough in the treatment of leukemia, especially in patients who are not eligible forintensive chemotherapy. In this review, we focused on the progress of immunotherapy in the field of AML by discussing monoclonal antibodies (mAbs), immune checkpoint inhibitors, chimeric antigen receptor T cells (CAR-T cells), and vaccine therapeutic choices.

Increasing access to allogeneic hematopoietic cell transplant: an international perspective.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a highly complex, costly procedure for patients with oncologic, hematologic, genetic, and immunologic diseases. Demographics and socioeconomic status as well as donor availability and type of health care system are important factors that influence access to and outcomes following allo-HCT. The last decade has seen an increase in the numbers of allo-HCTs and teams all over the world, with no signs of saturation. More than 80 000 procedures are being performed annually, with 1 million allo-HCTs estimated to take place by the end of 2024. Many factors have contributed to this, including increased numbers of eligible patients (older adults with or without comorbidities) and available donors (unrelated and haploidentical), improved supportive care, and decreased early and late post-HCT mortalities. This increase is also directly linked to macro- and microeconomic indicators that affect health care both regionally and globally. Despite this global increase in the number of allo-HCTs and transplant centers, there is an enormous need for increased access to and improved outcomes following allo-HCT in resource-constrained countries. The reduction of poverty, global economic changes, greater access to information, exchange of technologies, and use of artificial intelligence, mobile health, and telehealth are certainly creating unprecedented opportunities to establish collaborations and share experiences and thus increase patient access to allo-HCT. A specific research agenda to address issues of allo-HCT in resource-constrained settings is urgently warranted.