Haemopoetic Stem Cell Research Articles

From the Wright Brothers to the A380: Developing Transplantation Takes Teams of Teams.

From the Wright Brothers to the A380: Developing Transplantation Takes Teams of Teams.

Quantitative analysis of hemopoetic chimerism after living-related homogeneous hemopoetic stem cells transplantation

article: Quantitative analysis of hemopoetic chimerism after living-related homogeneous hemopoetic stem cells transplantation - Gazzetta Medica Italiana - Archivio per le Scienze Mediche 2021 October;180(10):539-44 - Minerva Medica - Journals

Induced pluripotent stem cells. Obtaining, properties and application prospects in biology and medicine

This review dedicated to induced pluripotent stem cells discovery of which became one of the outstanding achievements of biomedical science at the beginning of 21th century. These cells are in fact a artificially induced analogue of embryonic stem cells. They are the progenitors of all cells contained in organism of animals and human. The pool of embryonic stem cells forms in fertilized cell and they are involved in extremely complex processes of organogenesis. The position of these cells in general and of induced pluripotent stem cells in particular in hierarchy of cells in organism is described.The main properties of these cells, similarities and differences between embryonic and induced pluripotent stem cells, prospects for their practical use in biology and medicine including treatment of human diseases are considered.The mechanisms of induced dedifferenciation in both unipotent cells, for example fibroblasts and keretotinocytes, and multipotent cells as hemopoetic or mesenchimal stromal stem cells are described.In this review the information on used in the world approaches for obtaining of induced pluripotent stem cells is presented, the ways of reprogramming different in the methods of delivery of genetic material into the cells and conditions of their cultivation during dedifferentiation process and efficacy. As an example, description of all dedifferentiation cycle of human fibroblasts in induced pluripotent stem cells is provided. Besides, the data on unique properties of induced pluripotent stem cells what allowed to study ontogenesis processes, pathophysiology of various diseases both in vitro and in animals' models to be obtained using induced pluripotent stem cells and also on approaches of these cells application for medicine screening when they are synthesized and tested are given.

Determining the incidence of interstitial pneumonitis and chronic kidney disease following full intensity haemopoetic stem cell transplant conditioned using a forward-planned intensity modulated total body irradiation technique

Purpose/ObjectiveTotal body irradiation (TBI) remains a key component of conditioning for allogeneic haemopoietic stem cell transplant (HSCT), with interstitial pneumonitis (IP) and chronic kidney disease (CKD) important late sequelae. We undertook a retrospective service evaluation of TBI patients treated with a forward-planned intensity modulated radiotherapy technique (FP IMRT). Material/Methods74 adult patients were identified; all received step and shoot FP IMRT TBI, 14.4 Gy in 8 fractions over 4 days. Mean doses to the lungs and kidneys were 12–12.5 Gy. Toxicities were defined as per CTCAE v4.0: IP as multilobar infiltrates on CT with symptoms of dyspnoea, and renal dysfunction as an Estimated Glomerular Filtration rate (eGFR) < 60 ml/min/1.73 m2 for > 3 months. Secondary endpoints were overall survival (OS), progression free survival (PFS), cumulative incidence of non-relapse mortality (NRM), relapse risk and of acute and chronic GvHD. ResultsPatients received treatment for the following diagnosis: ALL/LBL (n = 37); AML (n = 33), CML-BC (n = 2) and High grade NHL (n = 2). The rate of IP due to any cause was 30%; positive microbiological evidence in 73% (16 /22). Idiopathic IP was seen in 8%, with only 4% (n = 3) having IP Grade ≥ 3.Two (4%) of 52 long term survivors developed CKD, one with thrombotic microangiopathy.4 year NRM was 16% (CI 11–32%); no treatment related deaths in matched sibling or umbilical cord blood HSCT. ConclusionFP IMRT TBI, reducing dose to the lungs and kidneys, has lower rates of idiopathic IP and CKD compared to the literature. This technique is safe and effective conditioning for full intensity HSCT.

The use of Autologous Haemopoetic Stem Cell Transplantation (AHSCT) in Multiple Sclerosis after Alemtuzumab treatment failure: a case series (2073)

The use of Autologous Haemopoetic Stem Cell Transplantation (AHSCT) in Multiple Sclerosis after Alemtuzumab treatment failure: a case series (2073)

Complications of Tyrosine Kinase Inhibitors Therapy in Chronic Myeloid Leukemia - Chronic Phase

Chronic myeloid leukaemia is a malignant tumor of pluripotent haemopoetic stem cell, characterized by increase granulocytes with left shift and the presence of the Ph chromosome.Treatment of chronic phase is made with tyrosine kinase inhibitors administered orally and can have secondary effects: haematological and non-haematological. The purpose of this paper is to assess complications of tyrosine kinase inhibitor therapy in chronic phase of chronic myeloid leukemia and establishing correlations with the type of inhibitor used. The study was performed on a total of 140 patients diagnosed with chronic phase CML in the Hematology Department of the City Clinical Emergency Hospital Timisoara between January 2006 - January 2016. The lot proposed has been studied in terms of anthropometric parameters and also the haematological and biochemical. It showed complications after initiation of therapy with tyrosine kinase inhibitors and also the correlations statistically significant between complications and type of inhibitor used. The study reveals that regardless the type of inhibitor used both haematological complications arise and non haematological. The most common are: neutropenia, thrombocytopenia, anemia, fluid retention, muscle and joint pain. Less common are nausea, diarrhea, abdominal pain, increased liver enzymes. Despite complications of occurring, these modern therapies significantly improve both survival and quality of life of patients.

Rhinosinusitis in Hurler syndrome patients requiring hematopoietic stem cells transplantation

Allogenic transplantation of hemopoetic stem cells (allo-THSC) is one of the most effective treatment methods for Hurler syndrome, aimed at maximal correction of complications related to the genetic disorder. Presence of infection in the recipient is an adverse risk factor, affecting the possibility of starting the conditioning regimen and THSC peforming in general. To assess the condition of the nasal cavity and paranasal sinuses in Hurler syndrome patients before the allo-THSC, dynamics of these changes after the transplantation taking into account the correction of alpha-L-iduronidase enzyme level with donor blood cells. From February 2012 to December 2017, In the Raisa Gorbacheva Research Institute of Child Oncology, Hematology and Transplantology of the Pavlov First Saint Petersburg State Medical University, eighteen Hurler syndrome patients (10 girls and 8 boys) received an allo-THSC. Median age at the time of the procedure was 23,5 months (min - 3,4; max - 24,8). Each patient with the shadowing of paranasal sinuses, rhinitis or nasal breathing difficulty received a standard rhinosinusitis treatment before the transplantation, effect of which was insignificant. Symptoms of rhinitis, condition of pharyngeal tonsil and paranasal sinuses were assessed before and auto the allo-THSC. In the post-allo-THSC, with the correction of alpha-L-iduronidase level each evaluated parameter has improved reliably (p-value < 0,05). Comparative analysis of the condition of the nasal cavity and pharyngeal tonsil before and after THSC was conducted on 14 patients out of 18. Rhinitis symptoms decreased in 9 (64,2%) patients; in 11 patients (78,5%) adenoids size reduced. Comparative analysis of the condition of paranasal sinuses was possible in 12 patients out of 18. Sinuses aeration improved in eight (66,6%) if patients. Nasal cavity and paranasal sinuses changes in Hurler syndrome patients before and after allo-THSC is poorly studied. Our experience demonstrates the normalization of nasal cavity, pharyngeal tonsila and paranasal sinuses symptoms in the majority of the patients receiving allo-THSC. These symptoms are, it seems a consequence of the underlying disease.

The role of autologous hemopoietic stem cell transplantation in T-cell lymphoma. Hungarian data

T-cell lymphoma is a poor prognostic hematological malignancy. The generally used - not sufficiently effective - induction chemotherapy should be improved with consolidative autologous hemopoetic stem cell transplantation. The authors describe the role, place and effectiveness of transplantation in this disorder. One hundred thirty three autologous stem cell transplantations were performed in the last 22 years in Hungary. Detailed results are available from the last 6 years. In this period 43 transplantations were carried out in 4 Hungarian centers. Carmustine-etoposide-cytosine arabinoside-melphalan (BEAM) conditioning regimen was used in 95%. The transplantation was done mainly in complete remission (84%), 1 year after transplantation 65% of patients were still in complete remission. Eleven patients died, 82% of them have progressive disease. Brentuximab vedotin has already proved the effectiveness, several other chemoterapeutics, monoclonal antibodies, kinase inhibitors are under investigation. In certain cases allogeneic stem cell transplantation has real indication among therapeutic options. Orv Hetil. 2017; 158(41): 1615-1619.

EP-1142: Role of radiotherapy(RT) in patients undergoing haemopoetic stem cell transplant(HSCT) for lymphoma

EP-1142: Role of radiotherapy(RT) in patients undergoing haemopoetic stem cell transplant(HSCT) for lymphoma

Disseminated adenovirus infection following allogeneic haemopoetic stem cell transplantation – A report on the use of brincidofovir and 10 year retrospective review of an adult transplant cohort

No: 1752 Presentation at ESCV 2015: Oral 38 Salivirus Type 1 and Type 2 in patients with acute gastroenteritis, Germany S. Aldabbagh1,∗, I. Eckerle1, A. Muller2, E.L. Delwart3, A.M. Eis-Hubinger1 1 Institute of Virology, University of Bonn Medical Centre, Germany 2 Department of Neonatology and Pediatric Intensive Care, Childrens Hospital, University of Bonn Medical Centre, Germany 3 Blood Systems Research Institute, Department of Laboratory Medicine, University of California, USA Background: Salivirus (SaV-A) is a novel member of the family Picornaviridae and the only species within the novel picornaviral genus Salivirus. The virus was found in up to 9% of fecal samples from patients, mostly children, with gastroenteritis, with highest prevalences in Asian countries. Thus, the virus was suspected to cause acute gastroenteritis. Recently, a second type of SaV-A (SaVA2) was identified in a sewage sample from Thailand. Because no information is available on SaV-A infection in Western Europe, we analysed stool samples from patients with symptoms suspicious of acute viral gastroenteritis for SaV-A and evaluated the clinical course of SaV-A-positive individuals. Methods: A total of 3019 fecal samples from 1941 hospitalised patients with symptoms of acute gastroenteritis were analysed. Samples were collected during 2012–2013 at the University Hospital Bonn and were routinely screened by (RT-)PCR for human norovirus, sapovirus, astrovirus, rotavirus, and adenovirus. A SaVA real-time RT-PCR was designed targeting a conserved nucleotide sequence in the 5′-untranslated region. Positive results were verified by sequencing the viral capsid protein 1 gene allowing also typing of the virus andwhole genome sequencing. Medical records of SaV-A-infected patients were reviewed for clinical features and laboratory data. Results: SaV-A was detected in five unrelated patients, with viral concentrations ranging between 7.1×106 and 7.2×108 copies/g feces, in the absence of common gastroenteritis viruses. The viruses from four patients were classified as SaV-A1 while in one patient SaV-A2 was present. In none of the five patients SaV-A infection was considered as the major cause of the gastroenteritis symptoms. Conclusion: SaV-A infection can be detected in Germany,Western Europe, albeit at low levels. The detection of SaV-A2 in Europe suggests global spread of SaV-A2. Presence of SaV-A, even at high concentration, in a stool sample provides no conclusive evidence that SaV is the major cause of the patient’s gastroenteritis symptoms. http://dx.doi.org/10.1016/j.jcv.2015.07.048 Abstract No: 1526 Presentation at ESCV 2015: Oral 39 Disseminated adenovirus infection following allogeneic haemopoetic stem cell transplantation – A report on the use of brincidofovir and 10 year retrospective review of an adult transplant cohort I. Ramsay1,∗, C. Attwood2, D. Irish1, D. Lowe3, P.D. Griffiths1, Kyriacou Charalampia2 1 Department of Virology, Royal Free Hospital, London UK 2 Department of Haematology, Royal Free Hospital, London UK 3 Department of Immunology, Royal Free Hospital,

Serum REG3alpha and C-Reactive Protein Levels in Crohn's Disease Patients Undergoing Immunoablation and Autologous Hemopoetic Stem Cell Transplantation in the ASTIC Trial

Background: REG3α has been recently shown to be a highly accurate biomarker for graft-versus-host-disease (GvHD). Given the unmet need of such biomarkers in Crohn's disease (CD) and the similarities between CD and GvHD, we aimed at investigating the role of serum REG3α as a diagnostic and prognostic biomarker in CD patients undergoing autologous hemopoetic stem cell transplantation (HSCT) in the multicenter Autologous Stem Cell Transplantation International Crohn's Disease (ASTIC) trial and to compare it to C-reactive protein (CRP). Methods: Stored serum samples from the ASTIC trial were analyzed using a commercially available human PAP1 ELISA-kit to measure REG3α levels. CRP was available from prior analysis in the ASTIC trial. These levels were correlated with clinical and endoscopic disease activity as well as overall clinical and endoscopic outcome 1 year after autologous HSCT. Results: One hundred thirty two serum samples were available for analysis. The mean concentration of REG3α was 101.8 ng/ml (95% CI 22.6-258.3). No significant elevation of REG3α was found among patients with active disease compared to those in remission (106.3 vs. 91.4). Patients with moderate to severe endoscopic disease activity showed substantially, although not significantly elevated REG3α levels compared to those in remission (95.4 vs. 52.4, p = 0.052). Baseline serum REG3α levels of patients without clinical or endoscopic remission 1 year after HSCT were not elevated compared to those in remission (63.1 vs. 66.9, and 68.4 vs. 59.2, respectively). In contrast, CRP was significantly elevated in patients with active disease compared to patients in remission (14.1 vs. 6.0 mg/dl, p = 0.032). In addition, CRP was elevated, although not significantly, in patients with severe endoscopic disease compared to those in endoscopic remission (18.7 vs. 4.1, p = 0.062). Furthermore, baseline CRP was reduced in patients with clinical and endoscopic remission after HSCT compared to those without remission, although not significantly (8.8 vs. 21.4, n.s. and 8.1 vs. 12.4, n.s.). Conclusion: Given the divergent findings compared to GvHD, we conclude that serum REG3α is not an accurate diagnostic and predictive biomarker in CD patients undergoing HSCT. In contrast, CRP is a valuable biomarker in order to differentiate active disease from remission. However, CRP does not seem to be of prognostic value for HSCT outcome.

828 Prolonged Regression of Ileocolonic Crohn's Disease Following Autologous Haemopoetic Stem Cell Transplantation: Presentation on Behalf of the Astic Trialists

TNF-naive and -failure subgroups. Adverse events were comparable across treatment groups; serious adverse events were more common in the eldelumab 10 and 20 mg/kg groups (7.5% and 9.8%, respectively) compared with placebo (5.0%), driven by infusion-related events. Rates of infection were similar across all groups. Conclusion: Induction treatment with eldelumab 10 or 20 mg/kg IV demonstrated trends towards efficacy as assessed by both clinical and endoscopic endpoints. Safety signals were consistent with those reported previously for eldelumab.1,2 1. Sandborn WJ, et al. Gastroenterology 2014;146(Suppl 1):S-55. 2. Mayer L, et al. Gut 2014;63:442-50. Clinical efficacy

G408(P) Cytokine storm associated multi-organ failure with poor neurological outcome, during rituximab administration in a child with relapsed acute lymphoblastic leukaemia and ebv related lymphoproliferative disease

We present the case of a 6 year old boy, with relapsed Acute Lymphoblastic Leukaemia and subsequent matched unrelated bone marrow transplant. His Epstein Barr Virus (EBV) titres were significant 6 months post-transplant with evidence of EBV related lymphoproliferative disease. Following local protocols, Rituximab was used for therapy and within minutes of starting the infusion the patient suffered pyrexia, hypotension and seizures with subsequent multi-organ failure, due to a cytokine storm. Organ damage included fulminant hepatic failure, renal failure meriting dialysis, cardiac failure requiring inotropic support and a significant acute brain injury. There was significant neurological impairment with radiological and electrophysiological evidence of global brain cell damage. As a result of irreversible neurological injury, the focus of treatment was switched from curative to palliative. Cytokine storm is an immune mediated phenomenon, characterised by an overwhelming release of cytokines. This can produce a sepsis like response and may lead to multi-organ failure. Cytokines are normally produced by leucocytes as a response to an infective or inflammatory process and their main role is to induce leukopoeisis. Rituximab is an anti-CD20 monoclonal antibody that has been useful in treating EBV related lymphoproliferative disease. Rituximab triggers the rapid release of cytokines that may lead to a cytokine storm with maximum levels within 2 h from the start of the infusion. Cytokine storms are characterised by overproduction of immune mediators that in turn lead to cellular overactivation, increased endothelial permeability, polymorphonuclear neutrophil adhesion and migration. As there is lack of regulatory intervention, tissue congestion with activated leucocytes ensues which eventually causes parenchymal injury. Although we report multi-organ failure in this case, lungs and gut are the organs that are more commonly affected. The incidence of cytokine storm in paediatric oncology patients is not known. It has been associated with haemophagocytic lymphohistiocytosis, graft-versus-host disease following haemopoetic stem cell transplant and the use of certain monoclonal antibodies. As in this case, results of the cytokine storm can be catastrophic, despite early recognition.

OP018. Prolonged Deep Remission of Ileocolonic Crohn's Disease following Autologous Haemopoetic Stem Cell Transplantation, presented on behalf of all the ASTIC Trialists

OP018. Prolonged Deep Remission of Ileocolonic Crohn's Disease following Autologous Haemopoetic Stem Cell Transplantation, presented on behalf of all the ASTIC Trialists

The possibility of using combined stem transplantation for haemopoesis activation in old and mature laboratory animals under ionizing radiation

The aim of this work was to study the influence of the combined transplantation of stem cells (multipotent mesenchimal stromal and haemopoetic stem cells) on the haemopoesis of old and mature laboratory animals under ionizing radiation. The result of the experiment shows that combined transplantation causes erythropoiesis activation under physiological conditions, while it causes erythroid and granulocytopoesis activation under ionizing radiation conditions. Moreover, combined multipotent mesenchimal stromal (MMSCs) and haemopoetic stem cells (HSCs) transplantation leads to cytoprotective action on the myeloid tissue due to a decrease in cytogenetically changed cells in mature animals under ionizing radiation; in old animals this effect can be seen even under physiological conditions. Combined transplantation of MMSCs and HSCs can be used in mature and old laboratory animals under ionizing radiation for the haemopoesis activation.

Decreased Expression Levels of Tumor Suppressor MicroRNAs in Hairy Cell Leukemia

Hairy cell leukemia is a chronic, clonal disease of the hemopoetic stem cell. Although our knowledge on its pathogenesis has increased a lot during the previous years, further details are needed to provide a more personalized, and therefore more successful treatment for patients. New advancements in the growing field of epigenetics may contribute to the finding of novel therapeutic target molecules. Similarly to acute leukemia, hairy cell leukemia also possesses a unique microRNA expression pattern. Decreased levels of tumor suppressor microRNAs lead to the elevation of the expression levels of their oncogenic targets. During our investigations on the level of let-7b and miR-124 in the bone marrow sample of a patient suffering from hairy cell leukemia, decreased expression levels have been found in the case of both microRNAs. These alterations also influence the activity of the MAPK signaling pathway, resulting from the regulation of its members by microRNAs including those mentioned above. Our results support new details about the connection between altered microRNA expression levels and signal transduction pathways in hairy cell leukemia.

AUTOLOGOUS HAEMATOPOIETIC STEM CELL TRANSPLANTATION IN MS

<b>Introduction</b> Autologous Haemopoetic Stem Cell Transplantation (AHSCT) has been used worldwide for aggressive multiple sclerosis (MS). We describe our current experience using this procedure and our plans to develop this service. <h3>Methods</h3> Retrospective audit of AHSCT for MS from 2009–13. Patients were selected based on persistent clinical relapses, progressive neurological disability or MRI lesion activity despite use of disease-modifying treatments (DMTs). <h3>Results</h3> As of January 2013, 7 subjects (3 female) had received AHSCT. Mean age at diagnosis was 26.6 years (range 18–47) and disease length at transplant was 9.6 years (range 2–19). Subjects received on average 2.1 DMTs (range 1–5) prior to AHSCT. The procedure was well tolerated; complications included infection (3) and diarrhoea (1) during the transplant. After the procedure 3 subjects had infections. Follow-up was for a mean of 16 months (range 5–37) in 6 subjects. Clinically 3 were better and 3 were stable. The EDSS was improved in 4, stable&nbsp;in 1 and worse in 1. <h3>Conclusion</h3> AHSCT in this small cohort complications were tolerable and aggressive MS appeared to be stabilised. We have developed guidelines based on this experience and international consensus criteria from EBMT and CIBMTR for future of AHSCT at our centres.

OC-007 Haemopoetic Stem Cell Transplantation For Severe Resistant Crohn’s Disease: Preliminary Evidence For Durable Benefit

IntroductionThe Autologous Stem Cell Transplantation International Crohn’s Disease (ASTIC) Trial shows haemopoetic stem cell transplantation (HSCT) to be effective over one year in Crohn’s disease, but its durability remains to...

OC-043 Controlled trial of immunoablation and autologous haemopoetic stem cell transplantation in crohn's disease: interim report on behalf of the ASTIC trialists

IntroductionThe Autologous Stem Cell Transplantation International Crohn's Disease (ASTIC) Trial is a randomised controlled evaluation of the proposition that immunoablation and hemopoietic stem cell transplantation improves the course of Crohn's...

1162 Controlled Trial of Immunoablation and Autologous Haemopoetic Stem Cell Transplantation in Crohn's Disease: Interim Report on Behalf of the Astic Trialists

Introduction The Autologous Stem Cell Transplantation International Crohn9s Disease (ASTIC) Trial is a randomised controlled evaluation of the proposition that immunoablation and hemopoietic stem cell transplantation improves the course of Crohn9s disease. Recruitment of all 48 patients in the trial will complete in early 2012 and results to date are presented descriptively here. Methods Patients with impaired quality of life due to active Crohn9s disease, despite at least three immunosuppressive agents all receive mobilisation treatment (intravenous cyclophosphamide 4 gm/m 2 over 2 days followed by recombinant human granulocyte-colony stimulating factor [GCSF, filgrastim], 10 μ/kg daily before randomisation to immediate (1 month) or delayed (1 year) immunoablation and stem cell transplantation. The conditioning regime is intravenous cyclophosphamide 50 mg/kg per day for 4 days, anti-thymocyte globulin 2.5 mg/kg/day and methyl prednisolone 1 mg/kg on days 3–5. The bone marrow is reconstituted by infusion of an unselected graft of 3–8×106/kg CD34 positive stem cells. Results are compared 1 year after mobilisation alone or after transplantation. Results Twelve months after stem cell transplantation (early or delayed) the Crohn9s Disease Activity Index (CDAI) fell from 324 (median, IQR 229–411) to 161 (85–257, n=17) compared to 351 (287–443) to 272 (214–331) following mobilisation alone (n=11). Six patients had a normal CDAI after transplantation vs one after mobilisation. C reactive protein fell from 16.6 (6.7–32.0) mg/l to 6.5 (3.5–12.5) mg/l vs 14 (8.0–27.0) mg/l to 9.0 (2.0–23.4) mg/l following mobilisation alone. The Crohn9s Disease Endoscopic Index of Severity (CDEIS) (aggregate for upper and lower endoscopy) fell from 18 (10–25) to 5 (1–11) following transplantation vs 14 (12–16) to 9 (4–22) following mobilisation. Three patients achieved the goal of a normal CDAI, no drug therapy and normal upper and lower endoscopy 1 year after tranplantation but so did one patient following mobilisation alone. Serious Adverse Events were common (n=100 to date) with 42 infective episodes requiring or prolonging hospitalisation, following both mobilisation and conditioning and transplantation. There were seven episodes of viral (re)activation. Temporary flare of Crohn9s disease activity or a need for surgery occurred in eight patients. Conclusion Immunoablation and hemopoietic stem cell transplantation appears to be an effective treatment for some patients with Crohn9s Disease, although full results will be required for a firm conclusion. Risks are significant, making it potentially suitable for only a limited number of patients. Data from the whole trial will be needed to judge whether mobilisation alone has any benefits. Competing interests None declared.