Treatment Of Hematological Diseases Research Articles

Compassionate Communication and Advance Care Planning to improve End-of-life Care in Treatment of Haematological Disease ‘ACT’: Study Protocol for a Cluster-randomized trial

IntroductionTo support the implementation of advance care planning and serious illness conversations in haematology, a previously developed conversation intervention titled ‘Advance Consultations Concerning your Life and Treatment’ (ACT) was found...

Mitigating Female Aging Kidney Damage from Ischemic Reperfusion Injury Using Renal Progenitor Cells

Acute kidney injury (AKI) is a sudden event that damages the kidney and disrupts normal function by various causes, such as ischemia, exposure to substances, or obstructions. With AKIs affecting 1 out of 5 hospitalized patients and their association with increased risk of chronic kidney disease (CKD), finding an effective treatment for AKIs is of vital importance. One possible treatment for AKIs could be found within the realm of progenitor cell therapy. Progenitor cells are currently used in the treatment of hematological diseases with the burgeoning information on their possible uses for other disorders. The purpose of this study was to determine whether there is a resident population of renal progenitor cells (RPCs) within the kidney and if these cells can be utilized as an effective treatment to mitigate aging AKI by decreasing inflammation through alteration of the M1:M2 macrophage ratio. This study utilized 75-78 weeks old C57BL/6J female mice to determine if RPCs can reduce the damage caused by ischemic reperfusion (IR)-induced AKI. Kidneys were harvested from young female (40 days old) mice and digested in collagenase type 1 to remove connective tissue. Cells were sorted by flow cytometry, positively selected for c-Kit using magnetic nanoparticles, and subsequently stained for Sca1 and Oct4. Aging female mice underwent renal IR injury (IRI) by clamping off the renal artery and vein for 27 minutes. Following reperfusion, the triple-positive cells were suspended in DMEM and injected into the kidney over the course of 8 minutes to reduce the possibility of pressure necrosis. A separate group of mice was injected with saline to serve as control. The mice were monitored for 3 days at which point kidney function was assessed and tissue harvested for biochemical analysis. Our results indicated an increase in inflammatory cytokines IL-17, NF-κB, and IL-6 in IRI mice which were mitigated with RPCs treatment along with an increase in anti-inflammatory marker IL-10. Furthermore, an increase in M1 macrophage markers was measured in IRI, and a trending increase in M2 macrophage markers in IRI animals treated with RPCs. The kidney function of IRI animals treated with RPC showed improvement compared to IRI control. In summary, we found a population of cells positive for three progenitor cell markers: c-Kit, Sca1, Oct4, and treating IRI aging female kidney with these cells reduced inflammatory markers along with an increase in kidney function, suggesting RPCs promote recovery from AKI by reducing inflammation. Grant Support: DK116591. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

CRISPR-based genomic modification method in the treatment of hematological diseases

Mutations in hematopoietic stem cells are the main cause of most blood diseases. Hematopoietic stem cell transplantation, which is the main treatment for hematopoietic stem cell disorders ,brings many negative effects according to the clinical cases, such as high toxic side effects, limited donor source, high recurrence rate, and high treatment cost .CRISPR/Cas acts as an immune system in prokaryote that grants them an ability to resist invasion by exogenous mobile genetic elements (MGE), which is a new generation of gene editing technology after the appearance of TALEN and ZFN. The immune system functions in three steps: adaptation, expression, and interference. It enables genomic modification by unwinding the double strands of DNA and inducing DNA repair processes such as homologydirected repair (HDR) and/or non-homologous end joining (NHEJ). So, this paper discusses the utilization of Crispr system in the treatment of -hemoglobinopathy, Chronic myeloid leukemia (CML) , Hemophilia and summarizes the current limitations of this technology, such as the editing efficiency, potential immunogenicity of editing tools and off-target effects , while it still remains promising as to its future prospects for research. This technology is very likely to replace traditional therapies and achieve a complete cure for the blood disease.

CDK9 INHIBITORS: a promising combination partner in the treatment of hematological malignancies.

Most hematological malignancies are characterized by overexpression of certain cancer promoting genes, such as MYC, MCL1 and cyclin D1. Preclinical studies in animal models have shown that CDK9 inhibitors supress the transcription of these anti-apoptotic and pro-survival proteins, and suggest their potential synergism with other drugs. In its first in-human trial, enitociclib demonstrated clinical activity in a small cohort of patients with high grade B lymphoma with MYC and BCL2 and/or BCL6 rearrangements, inducing complete responses in 2 of 7 subjects (29%) in monotherapy. These data suggest CDK9 inhibitors could play a role in the treatment of hematological diseases and could be a great ally when combined with other therapeutic approaches.

Post-translational modifications confer amphotericin B resistance in Candida krusei isolated from a neutropenic patient.

Neutropenia is a common complication in the treatment of hematological diseases and the most common predisposing factor for invasion by fungi, such as Candida krusei. Recent studies have shown that C. krusei, a life-threatening pathogen, has developed resistance to amphotericin B (AMB). However, the mechanisms that led to the rapid emergence of this AMB-resistant phenotype are unclear. In this study, we found the sensitivity for AMB could be promoted by inhibiting histone acyltransferase activity and western blot analysis revealed differences in the succinylation levels of C. krusei isolated from immunocompromised patients and of the corresponding AMB-resistant mutant. By comparative succinyl-proteome analysis, we identified a total of 383 differentially expressed succinylated sites in with 344 sites in 134 proteins being upregulated in the AMB-resistant mutant, compared to 39 sites in 23 proteins in the wild-type strain. These differentially succinylated proteins were concentrated in the ribosome and cell wall. The critical pathways associated with these proteins included those involved in glycolysis, gluconeogenesis, the ribosome, and fructose and mannose metabolism. In particular, AMB resistance was found to be associated with enhanced ergosterol synthesis and aberrant amino acid and glucose metabolism. Analysis of whole-cell proteomes, confirmed by parallel reaction monitoring, showed that the key enzyme facilitating lysine acylation was significantly upregulated in the AMB-resistant strain. Our results suggest that lysine succinylation may play an indispensable role in the development of AMB resistance in C. krusei. Our study provides mechanistic insights into the development of drug resistance in fungi and can aid in efforts to stifle the emergence of AMB-resistant pathogenic fungi.

BML-260 promotes the growth of cord blood and mobilized peripheral blood hematopoietic stem and progenitor cells with improved reconstitution ability.

Hematopoietic stem cells (HSCs), which are multipotent and have the ability to self-renew, are frequently used in the treatment of hematological diseases and cancer. Small molecules that target HSC quiescence regulators could be used for ex vivo expansion of both mobilized peripheral blood (mPB) and umbilical cord blood (UCB) hematopoietic stem and progenitor cells (HSPC). We identified and investigated 35 small molecules that target HSC quiescence factors. We looked at how they affected HSC activity, such as expansion, quiescence, multilineage capacity, cycling ability, metabolism, cytotoxicity, and genotoxicity. A transplantation study was carried out on immunocompromised mice to assess the expanded cells' repopulation and engraftment abilities. 4-[(5Z)-5-benzylidene-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]benzoic acid (BML)-260 and tosyl-l-arginine methyl ester (TAME) significantly increased both mPB and UCB-HSPC content and activated HSC re-entry into the cell cycle. The improved multilineage capacity was confirmed by the colony forming unit (CFU) assay. Furthermore, gene expression analysis revealed that BML-260 and TAME molecules aided HSC expansion by modulating cell cycle kinetics, such as p27, SKP2, and CDH1. In addition to these in vitro findings, we discovered that BML-260-expanded HSCs had a high hematopoietic reconstitution capacity with increased immune cell content after xenotransplantation into immunocompromised mice. In addition to the BML-260 molecule, a comparison study of serum-containing and serum-free chemically defined media, including various supplements, was performed. These in vitro and xenotransplantation results show that BML-260 molecules can be used for human HSC expansion and regulation of function. Furthermore, the medium composition discovered may be a novel platform for human HSPC expansion that could be used in clinical trials.

Reference intervals for erythrocyte parameters and hemoglobin electrophoresis parameters for young children in Guangxi.

Erythrocyte parameter analysis is the important means for diagnosis and treatment of hematological diseases, which are essential for screening of thalassemia in southern China combined with hemoglobin electrophoresis analysis. But little is known regarding the reference intervals (RIs) in healthy pediatrics in these two areas. 95% RIs of erythrocyte parameters were calculated from 853 healthy preschoolers, aged from 1 days to <6 years, according to the C28-A3C guidelines of the Institute of Clinical and Laboratory Standards. To express the magnitude of sex and age variation, standard deviation ratio (SDR) was calculated using ANOVA. Concurrently, we selected 3814 thalassemia carriers as carriers group and drew receiver operating characteristic (ROC) curves to establish the optimal cut-off values of hemoglobin electrophoresis parameters, which were used as the upper/lower limits of RIs to efficiently screen thalassemia. All parameters except red blood cell (RBC) required age partitioning, confirmed by SDRage above .4. There was no need for sex partitioning on all parameters, confirmed by SDRsex below .4. The optimal cut-off value of Hemoglobin A2 (Hb A2) in the four subgroups was <7.8% (Hb A), 2.3%-3.2%, 2.5%-3.6% and 2.6%-3.6%, respectively. In this study, the establishment of RIs improved the diagnostic efficiency of hematological disease (especially thalassaemia) for children in Guangxi. It provides reliable hematological references for the identification and diagnosis, treatment monitoring, and health screening of children's clinical diseases.

Gene-modified T cell therapy for cancer: Current challenges and potential solutions

Immunotherapy has achieved significant breakthroughs in patients with hematological diseases and various cancers. The adoptive transfer of T cells, especially gene-modified T cells such as chimeric antigen receptor T (CAR-T) cells and T cell receptor-engineered T (TCR-T) cells, is developing rapidly. Since 2017, eight CAR-T cell products have been approved for the treatment of hematological diseases, such as refractory or relapsed acute B lymphoblastic leukemia, specific subtypes of B cell lymphoma, and multiple myeloma. The first TCR-T cell product, Kimmtrak, was approved for the treatment of unresectable or metastatic uveal melanoma in March 2022. However, there are still many problems, including side effects, relapse, high demand for individualization, and expensive cost in hematological diseases, tumor heterogeneity, antigen escape, poor immune cell infiltration ability, immunosuppressive microenvironment, and low response in solid tumors. With the in-depth exploration of tumor immunology and the development of genetic engineering technology, many novel strategies for improving the anti-tumor effect and safety of gene-modified T cell immunotherapy have been attempted. This paper presents a systematic review of the literature on CAR-T cell and TCR-T cell therapy, focusing on applications, clinical trials, problems, and potential solutions.

Purification of CD34+ cells in myasthenia gravis patient’s peripheral blood stem cells using the CliniMACS cell separation system

Autologous hematopoietic stem cell transplantation therapy has been widely used in recent decades for the treatment of hematological diseases, cancer, and autoimmune diseases. In autoimmune diseases, self-activated T lymphocytes and B lymphocytes secreting antibodies against host antigens are considered to be central in the pathogenesis of the disease. Autologous stem cell products that eliminates these pathological cells could be a lifesaver for patients with autoimmune diseases who are resistant to conventional therapy, in order to restore a healthy immune system, achieve long-term remission and limited recurrence. The aims of this study was to complete and evaluate the results of the CD34 positive stem cells purification procedure from a myasthenia gravis patient’s mobilized peripheral blood stem cells, for the purpose of autologous hematopoietic stem cell transplantation for Myasthenia gravis as well as other autoimmune diseases in Vietnam. We have completed the purification procedure of CD34-positive stem cells from mobilized peripheral blood stem cells of patient with myasthenia gravis using CliniMACS system with results of removing 99.99% of T lymphocytes; 99.81% of B lymphocytes; 99.99% of NK cells, while CD34+ recovery performance was 64.05% with CD34+ cell survival rate of over 99%, no bacterial contamination, ensuring quality assurance of stem cell product for transplantation.

Optimizing allogeneic grafts in hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is widely used in the treatment of hematological diseases. It is well known that allogeneic grafts play a key role in predicting transplantation prognosis. Hematopoietic stem cells (HSCs) are a functional part of grafts and are capable of reconstructing hematopoiesis and immunity, but purified HSCs have not been identified or isolated to date. In clinical practice, allogeneic grafts have been optimized to improve transplantation outcomes. The optimized grafts are considered to engraft successfully, reconstruct immunity rapidly, and exert a graft‐vs‐leukemia (GVL) effect without causing severe graft‐vs‐host disease (GvHD). In the last several decades, considerable efforts have been made in searching for optimized grafts based on different graft manipulation approaches and different graft sources. Currently, there is no uniform standard for optimized grafts in allogeneic transplantation. In the future, sorting out the cellular elements responsible for the effects of allo‐HSCT might be a research direction for further optimization of grafts. In this review, we propose the concept of optimized grafts and summarize the recent advances made in the process of optimizing grafts.

Human Glioma Cells Therapy Using ATRA-Induced Differentiation Method to Promote the Inhibitive Effect of TMZ and CCDP.

The glioma stem cells (GSCs) performed the self-renewal, proliferation, and differentiation characteristics; their drug resistance has become the main reason for glioma clinical treatment failure. All-trans retinoic acid (ATRA) is an important inducer of cell differentiation, applied in the treatment of hematologic diseases and other solid tumors. ATRA is a fat-soluble compound, which can easily go through the blood-brain barrier. Therefore, in this study, ATRA was used to induce the differentiation of glioma cells and glioma stem cells, reducing the degree of malignancy and improving its chemotherapy resistance. Methods and Treatment. The results of IF and PCR showed that the expression of CD133 was significantly lower than those of undifferentiated cells. Furthermore, temozolomide (TMZ) and cisplatin (CDDP), the first-line drugs, were used for the treatment of GCs and GSCs. The MTT assay results showed that the effect of the combination of the two drugs was significantly stronger than that of one of them alone. Results. Moreover, the MTT assay also demonstrated that TMZ single, CDDP single, and the combination of TMZ and CDDP can inhibit the proliferation of GCs, ATRA-GCs, GSCs, and ATRA-GSCs in a dose- and time-dependent manner; and ATRA-induced differentiation could promote those drugs inhibition effect and increased the chemotherapy sensitivity. Conclusion. Therefore, we successfully purified the suspension spherical glioma stem cells. Moreover, ATRA was demonstrated to induce the differentiation of GCs and GSCs. Furthermore, ATRA-induced differentiation promotes the inhibitive effect of TMZ and CCDP treatment on the proliferation of primary human glioma cells and glioma stem cells, suggesting that ATRA could increase the chemotherapy sensitivity of TMZ and CCDP through inducing cell differentiation. The combination of TMZ and CCDP performed a synergistic role in inhibiting the proliferation of GCs and GSCs.

Invasive Mucormycosis in Patients with Hematological Diseases Identified in the Global Fungiscope Registry

Background:Invasive fungal diseases (IFD) are a frequent complication in hematological patients. Hematological malignancies and their treatment are main risk factors for IFD. Less frequent IFD, such as invasive mucormycoses (IM), are increasing worldwide and are associated with mortality up to 100%. Efficient diagnostic and treatment approaches for IM are not known or validated yet. Thus, it is urgent to better understand clinical presentation and management of IM in hematological patients to eventually improve patient outcome.Methods:Clinical data on IM were collected in FungiScope, an international web-based registry. Cases with cultural, histological or molecular evidence of IM are enrolled. Data collected include demographics, underlying conditions and their treatment, clinical signs and symptoms, sites of infection, diagnostic tests, antifungal treatment and outcome. Clinical isolates are collected for centralized identification, molecular analyses and exchange between collaborators.Results:To date, 194 cases of IM with an underlying hematologic disease (HD) were captured in the FungiScope database. AML, ALL, Non-Hodgkin's Lymphoma and CLL were the most frequent malignancies (50.5%, 16%, 5.6%, and 5.6%, respectively). Treatment of HD was chemotherapy in 76%, for 72% of these it was the primary course. Prolonged neutropenia (>10 days) was reported in 70% of cases (information available for 111 cases). The majority of patients received antifungal agents (94.3%; median 55 days, range 0 to 750 days) and 37% underwent surgical debridement. Antifungals known to be active against Mucorales (amphotericin B, isavuconazole, itraconazole, posaconazole) were administered in 82.5% of cases, in 16% of those amphotericin B was used as a single agent once the pathogen had been identified. Overall mortality was 62.4% and death due to IM was reported for 74% of cases. Mortality in patients receiving antifungals active against Mucorales was 56%. Median follow-up time was 45 days (range 0-2110 days). Favourable response (complete or partial response or stable disease) was present in 44% of all cases. Due to premature death, twelve patients did not receive antifungal therapy.Conclusion:The FungiScope registry is a feasible approach to collect data on a relevant amount of rare cases of rare IFD. IM remains a life threatening disease in hematological patients. Despite aggressive antifungal treatment strategies, outcome remains poor. More effective treatment strategies are urgently needed to improve patient outcome. DisclosuresKarthaus:Riemser: Honoraria, Other: Travel grant; HELSINN: Honoraria, Other: Travel grant. Vehreschild:Pfizer, MSD/ Merck, Gilead Sciences, Organobalance and Astellas Pharma: Speakers Bureau; 3M, Astellas Pharma, DaVolterra and Gilead Sciences: Research Funding; Berlin Chemie, MSD/Merck and Astellas Pharma: Consultancy. Meißner:Accelerate Diagnostics: Honoraria. Wisplinghoff:Beckmann, BioMerieux, Bruker Daltonics, Cepheid, Hologic, i-Sense, r-biopharm, Siemens, Specific Technologies: Research Funding; Beckmann, BioMerieux, Bruker Daltonics, Cepheid, Hologic, i-Sense, r-biopharm, Siemens, Specific Technologies: Consultancy; Beckmann, BioMerieux, Bruker Daltonics, Cepheid, Hologic, i-Sense, r-biopharm, Siemens, Specific Technologies: Honoraria. Vehreschild:Pfizer, Merck, Gilead, Basilea and Astellas: Speakers Bureau; Astellas, Gilead, Infectopharm, Merck/MSD, Basilea and Pfizer: Research Funding; Astellas, Gilead, Basilea and Merck/MSD: Consultancy. Cornely:Anacor, Amplyx, Actelion, Astellas, Basilea, Cidara, Da Volterra, F2G, Gilead, Janssen Pharmaceuticals, Matinas, Menarini Ricerche, Merck/MSD, Paratek Pharmaceuticals, Scynexis, Seres, Summit, Vical, Vifor: Consultancy; Actelion, Aramis Pharma, Astellas, AstraZeneca, Basilea, Bayer, Cidara, Duke University (NIH UM1AI104681), F2G, Gilead, GSK, Leeds University, MedPace, Melinta Therapeutics, Merck/MSD, Miltenyi, Pfizer, Rempex, Roche, Sanofi Pasteur, Scynexis, Seres Thera: Research Funding; Astellas, Basilea, Gilead and Merck/ MSD: Honoraria. Seidel:Basilea and Astellas: Other: Travel grant.

Biological Characteristics of Umbilical Cord Mesenchymal Stem Cells and Its Therapeutic Potential for Hematological Disorders.

Umbilical cord mesenchymal stem cells (UC-MSCs) are a class of multifunctional stem cells isolated and cultured from umbilical cord. They possessed the characteristics of highly self-renewal, multi-directional differentiation potential and low immunogenicity. Its application in the field of tissue engineering and gene therapy has achieved a series of results. Recent studies have confirmed their characteristics of inhibiting tumor cell proliferation and migration to nest of cancer. The ability of UC-MSCs to support hematopoietic microenvironment and suppress immune system suggests that they can improve engraftment after hematopoietic stem cell transplantation, which shows great potential in treatment of hematologic diseases. This review will focus on the latest advances in biological characteristics and mechanism of UC-MSCs in treatment of hematological diseases.

Impact of Smoking Behavior on Survival Following Allogeneic Hematopoietic Stem Cell Transplantation - Smoking Cessation Matters.

There are only a few data on the impact of smoking and smoking cessation on the outcome of patients treated with allogeneic hematopoietic stem cell transplantation, a well-established therapy for hematologic malignancies. In a retrospective cohort study design we examined the impact of smoking and smoking cessation on survival among 309 eligible consecutive adults who underwent allogeneic hematopoietic stem cell transplantation using reduced-intensity (n = 179) or myeloablative (n = 130) conditioning between 1999 and 2018. Smoking and was independently associated with increased mortality with a five-year overall survival of 25% in current smokers versus 53% in never smokers versus 48% in past smokers. Never smokers lived significantly longer (HR: 2.00, 95%CI: 1.19-3.35, p = .008) and had a better event-free survival (HR: 2.11, 95%CI: 1.27-3.49, p = .004) than current smokers. In the long run, never smokers also lived significantly longer than past smokers (HR: 1.45, 95%CI: 1.16-1.81, p = .001). Patients who quit smoking before allogeneic hematopoietic stem cell transplantation showed a tendency towards increased survival compared to those who continued smoking (HR: 1.53, 95%CI: 0.95-2.45, p = .078). In relation to life-time cigarette dose smokers with low-dose (1-10 pack-years) cigarette consumption lived significantly longer (HR: 1.60, 95%CI: 1.03-2.50, p = .037) and had a better event-free survival (HR: 1.66, 95%CI: 1.07-2.58, p = .025) than patients with high-dose (≥10 pack-years) cigarette consumption. In allogeneic hematopoietic stem cell transplantation for hematologic malignancies, smoking history per se, lifetime cigarette dose, and continued smoking, were significantly associated with increased all-cause mortality and reduced event-free survival. Continued and past smoking represent established risk factors for malignant and non-malignant diseases, however, they are also a strong risk factor for a poor outcome after allogeneic hematopoietic stem cell transplantation for hematologic diseases. Our study shows that the hazard ratio for death after such transplantation is doubled if patients continue smoking and even if they have quit smoking, their risk remains significantly elevated. This suggests that the smoking history provides important predictive factors for the outcome of allogeneic hematopoietic stem cell transplantation and that smoking cessation should be implemented in the treatment of hematologic diseases as early as possible.

Prognostic factors for neutrophil engraftment after haploidentical cell transplantation with PT-Cy in patients with acute myeloid leukemia in complete remission, on behalf of the ALWP-EBMT.

The use of haplo-HCT with posttransplant cyclophosphamide (PT-Cy) is a new standard in the treatment of hematological diseases. A paucity of data exists on risk factors for engraftment failure in haplo-HCT with PT-Cy. We analyzed 1939 adults with acute myeloid leukemia (AML) who received a first haplo-HCT from 2010 to 2019. Status at haplo-HCT was first complete remission (CR1) in 72.5% of patients, secondary AML was reported in 9.9%. Median follow-up was 24.4 months and median age at haplo-HCT was 51 years. Stem cell source was bone marrow (BM) in 42% and peripheral blood stem cell (PBSC) in 58%, and 64% of patients received a myeloablative conditioning (MAC) regimen. Cumulative incidence of primary graft failure (GF) was 6%; GF was reported in 110 patients and 54 died before day +30 with no sign of cell recovery. Overall, 33 patients underwent a second HCT in a median time of 45 days and 13 were alive at last follow-up, the 2-year overall survival (OS) after second HCT being 32.4%. In multivariate analysis, factors independently associated with the risk of nonengraftment were: secondary AML (HR 1.30, p = 0.003), use of RIC (HR 1.22, p < 0.001), and use of BM (HR 1.21, p < 0.001). At 2 years, leukemia-free survival (LFS) and OS for the entire population was 55.2% (95% CI: 52.6-57.6) and 60.9% (95% CI: 58.4-63.3), respectively. Incidence of GF after haplo-HCT with PT-Cy is lower than reported T-cell-depleted haplo-HCT. Optimization of conditioning regimen and graft source should be considered for reducing the risk of GF in haplo-HCT recipients using PT-Cy.

The Role of mTOR Inhibitors in Hematologic Disease: From Bench to Bedside.

The mTOR pathway plays a central role in many cellular processes, such as cellular growth, protein synthesis, glucose, and lipid metabolism. Aberrant regulation of mTOR is a hallmark of many cancers, including hematological malignancies. mTOR inhibitors, such as Rapamycin and Rapamycin analogs (Rapalogs), have become a promising class of agents to treat malignant blood diseases—either alone or in combination with other treatment regimens. This review highlights experimental evidence underlying the molecular mechanisms of mTOR inhibitors and summarizes their evolving role in the treatment of hematologic disease, including leukemia, lymphoma, myeloma, immune hemocytopenia, and graft-versus-host disease (GVHD). Based on data presented in this review, we believe that mTOR inhibitors are becoming a trusted therapeutic in the clinical hematologist’s toolbelt and should be considered more routinely in combination therapy for the management of hematologic disease.

Cardio-oncology and Oncohematology: Examination Algorithms, Prophylactic and Treatment of Cardiotoxicity, Trends in Rehabilitation

Successful chemotherapy in the treatment of hematological diseases is determined not only by the efficacy of antitumor drugs, but by the timely correction of adverse events, among which especially important are cardiac complications associated with both already existing cardiovascular diseases and cardiotoxicity of cytostatic drugs. Of particular importance is also a frequent lack of systemic cardiological examination of oncohematological patients. The urgency of this issue was the reason for creating cardio-oncological clinics focused on the closest co-operation of cardiologists with drug chemotherapy experts. Hematological patients are a particular group among chemotherapy recipients. Potential curability of an oncohematological disease and achieving durable MRD-negative remission raise the importance of irreversible or long-term cardiac complications directly affecting the quality of life and life expectancy. Besides, in some cases long-term or life-long administration of certain cardiotoxic antitumor drugs requires a particular cardiological follow-up. A broad variety of cardiotoxic effects of antitumor drugs and peculiarities of their clinical manifestations call for the exact algorithms of cardiological examination to be observed for the timely detection and treatment of cardiovascular complications. The now available st udies and interdisciplinary work of cardiologists and oncologists (oncohematologists) can yield such algorithms for examination and the approaches to prophylactic and treatment of cardiotoxicity as well as to rehabilitation of patients.

WITHDRAWN: Cellular and gene therapy for the treatment of hematologic diseases and solid tumors: The dawn of a new era

WITHDRAWN: Cellular and gene therapy for the treatment of hematologic diseases and solid tumors: The dawn of a new era

Targeted Delivery of Erythropoietin Hybridized with Magnetic Nanocarriers for the Treatment of Central Nervous System Injury: A Literature Review.

Although the incidence of central nervous system injuries has continued to rise, no promising treatments have been elucidated. Erythropoietin plays an important role in neuroprotection and neuroregeneration as well as in erythropoiesis. Moreover, the current worldwide use of erythropoietin in the treatment of hematologic diseases allows for its ready application in patients with central nervous system injuries. However, erythropoietin has a very short therapeutic time window (within 6–8 hours) after injury, and it has both hematopoietic and nonhematopoietic receptors, which exhibit heterogenic and phylogenetic differences. These differences lead to limited amounts of erythropoietin binding to in situ erythropoietin receptors. The lack of high-quality evidence for clinical use and the promising results of in vitro/in vivo models necessitate fast targeted delivery agents such as nanocarriers. Among current nanocarriers, noncovalent polymer-entrapping or polymer-adsorbing erythropoietin obtained by nanospray drying may be the most promising. With the incorporation of magnetic nanocarriers into an erythropoietin polymer, spatiotemporal external magnetic navigation is another area of great interest for targeted delivery within the therapeutic time window. Intravenous administration is the most readily used route. Manufactured erythropoietin nanocarriers should be clearly characterized using bioengineering analyses of the in vivo size distribution and the quality of entrapment or adsorption. Further preclinical trials are required to increase the therapeutic bioavailability (in vivo biological identity alteration, passage through the lung capillaries or the blood brain barrier, and timely degradation followed by removal of the nanocarriers from the body) and decrease the adverse effects (hematological complications, neurotoxicity, and cytotoxicity), especially of the nanocarrier.

Posterior Reversible Encephalopathy Syndrome in Childhood Hematological/Oncological Diseases: Multicenter Results.

The aim of the study was to analyze the characteristics of posterior reversible encephalopathy syndrome (PRES) cases treated at 10 different institutions in our country. Fifty-eight patients diagnosed with PRES were included in this study. The data of PRES cases from 10 departments of pediatric hematology/oncology were analyzed. The mean age of the patients at the time of diagnosis of PRES was 8.95±3.66 years. Most patients (80.4%) had a primary diagnosis of acute leukemia. Patients received chemotherapy (71.4%) and/or used steroids within 14 days before the diagnosis of PRES (85.7%). Hypertension was found in 83.9% of the patients. Twenty-six patients had infections and 22 of them had febrile neutropenia. The most common electrolyte disorders were hypocalcemia, hypomagnesemia, and hypopotassemia. Six patients had tumor lysis syndrome and 4 had inappropriate antidiuretic hormone syndrome. Magnetic resonance imaging was used for diagnosis in all patients. The most commonly involved regions by magnetic resonance imaging were occipital (58%), parietal (51%), and frontal lobes (45%), respectively. Twenty-five patients required intensive care and 7 patients were intubated. In conclusion, PRES may develop during the follow-up and treatment of hematological diseases. In addition to steroid and intense combined chemotherapies, immunosuppressive agents and hypertension are also factors that may be responsible for PRES.