Wyniki wyszukiwania - Biblioteka Nauki

1

ESH Euroconference on translational research in transplantation: immunogenetics, pharmacogenomics, proteomics, and immunobiology

100%

Basak G. W. , Gronkowska A.

Archivum Immunologiae et Therapiae Experimentalis

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2006

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tom 54

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nr 6

427-429

EN

The ESH Euroconference on Translational Research in Transplantation was held July 4?6, 2006, in Paris, France. It was organized by the European School of Hematology to discuss the state of the art and perspectives of transplantation research. Major discussion topics were the future directions for basic science and clinical research.

2

Strategies of hepatocyte transplantation

63%

Ostrowska A.

Postępy Higieny i Medycyny Doświadczalnej

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2000

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tom 54

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nr 2

149-181

EN

Hepatic parenchymal cell transplantation is a promising method for managing patients with the acute liver failure and may create a bridge to whole organ grafting. Elimination or reduction of the immunogenicity of the hepatocytes would permit long-term graft survival without the neet of non-specific immunosuppression. The presented experimental evidence suggests that the modulation of hepatocyte immunogenicity by purification and cryopreservation reduces the allorespense to hepatocytes both in vitro and in vivo.Identification of inoculated cells facilitates long-term monitoring of their localization and metabolic activity.

3

Neural commitment of cord blood stem cells (HUCB-NSC/NP): Therapeutic perspectives

51%

Domanska-Janik K. , Habich A. , Sarnowska A. , Janowski M.

Acta Neurobiologiae Experimentalis

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2006

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tom 66

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nr 4

279-291

EN

Human umbilical cord blood (HUCB) is considered a promising source of neural progenitors capable of being used for cellular therapies in neurological disorders. Here we review briefly our work on the elucidation of mechanisms and development of practical standards as regards the selection, maintenance and use of cord blood derivatives for such purposes. Our results join those of other recent studies in suggesting strongly that, the generation of neural-like cells from tissue belonging to a different germ layer (such as a cord blood is) is most probably explained by reference to a discrete subpopulation of embryonic-like stem cells of pluripotent characteristics. Such cells identified in cord blood through their expression of specific genetic and protein markers can be expanded in vitro and directed toward neurally-committed progenitors differentiating further into more mature neuron-like or macroglia-like cell phenotypes. From this HUCB-derived neural progenitor fraction a novel neural-like stem cell line (HUCB-NSC) has been developed, and characterized in respect of in vitro and in vivo (post-transplantation) properties.

4

Biohybrid artificial organs in therapy of systemic disorders

51%

Jankowski T.

Biotechnologia

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1999

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nr 1

45-58

EN

Transplantation of cells and tissues secreting a desirable therapeutic product shows a potential in the treatment of many human diseases such as diabetes, hemophilia, dwarfism, immunodeficiencies, anemia, hypocalcemia, and some neurodegenerative disorders. To avoid graft rejection, the transplanted tissue is immunoisolated in a semipermeable membrane, thereby creating an implantable biohybrid artificial organ. A number of encapsulation systems such as vascular implants, diffusion chambers, and microcapsules have been developed for cell therapy. The encapsulation membrane should allow for diffusion of nutrients, dissolved gases, and wastes and should be impermeable to the components of the immune system, including cellular and humoral components. Encapsulation cell technology offers a solution to the problem of donor organ supply, not only by potentially allowing the transplantation of cells and tissues without immunosuppresion, but also by permitting use of tissue isolated from animals. However, further research is required in the areas of encapsulation device design and tissue supply from primary or cell-culture sources.

5

Viral infections in children after allogenic stem cells transplantation

51%

Rybka K. , Turkiewicz D.

Postępy Higieny i Medycyny Doświadczalnej

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2003

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tom 57

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nr 1

3-17

EN

Allogeneic hematopoietic cell transplantation (alloHCT) is the treatment of choice for various pediatric malignancies and nonmalignant diseases. The most prominent complication of allotransplantation is graft vs host disease (GvHD). The treatment of GvHD influence negatively function of immune system and increase risk of bacterial, fungal and viral infections. Clinical symptoms of viral infection may mimic GvHD and lead to inappropriate treatment. Human ctomegalovirus (CMV, Herpesviridae) has been recognized as most important viral pathogen after alloHCT. Increasing number of procedures, especially from alternative donors, requiring more intensive immunosuppression, led to identification more viral pathogens causing transplant related mortality and morbidity. Among them are adenoviruses (ADV, Adenoviridae), BK and JC viruses (Papovaviridae) and human herpes virus 6 (HHV-6, Herpesviridae). Frequency of complications caused by those pathogens is higher in children then in adults.

6

Predicting outcome in haematological stem cell transplantation

51%

Dickinson A. M. , Cavet J. , Cullup H. , Wang X. N. , Jarvis M. , Sviland L. , Middleton P. G.

Archivum Immunologiae et Therapiae Experimentalis

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2002

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tom 50

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nr 6

369-376

EN

This present review summarises recent results investigating the role of certain cytokine gene polymorphisms, including TNF, IFN, IL-6, IL-10 and IL1 Ra, in allogeneic stem cell transplantation. The review discusses their role in predicting outcome and the development of a genetic risk index for Graft versus Host Disease in HLA matched sibling transplants. By the comparative use of an in vitro human skin explant model initial results suggest that certain cytokine gene polymorphisms may be associated with more severe disease.

7

Immunomodulatory effects of HMG-CoA reductase inhibitors

51%

Danesh F. R. , Anel R. L. , Zeng L. , Lomasney L. , Sahai A. , Kanwar Y. S.

Archivum Immunologiae et Therapiae Experimentalis

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2003

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tom 51

|

nr 3

139-148

EN

3-Hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors or statins are competitive inhibitors of the rate limiting enzyme in cholesterol synthesis. Several clinical trials have shown a marked reduction in cholesterol levels associated with decreased cardiovascular mortality in patients treated with statins. However, more recent observations have suggested that the clinical benefits of statins may be, at least in part, independent of the effect of statins on cholesterol synthesis. These so-called pleiotropic or cholesterol-independent effects of statins could be the result of reduction in the formation of intermediaries in the mevalonate pathway as statins by inhibiting L-mevalonic acid synthesis also prevent the production of isoprenoids in the cholesterol biosynthetic pathway. Isoprenoids serve as important lipid attachments for the posttranslational modification of a variety of proteins such as small GTP-binding proteins of the Ras superfamily implicated in intracellular signaling. The list of different pleitropic effects of statins is still growing and include among others direct effects of statins on modulating endothelial function, decreasing oxidative stress, and more recently anti-inflammatory and immunomodulatory actions of statins. For instance, statins decrease T cell activation, the recruitment of inflammatory cells into atherosclerotic lesions, and inhibit IFN-gamma expression of MHCII on antigen-presenting cells. This review article summarizes the anti-inflammatory and immunomodulatory effects of statins and thus provides a new rationale to use statins as a new class of immunosuppressive agents.

8

Impact of fetal -maternal tolerance in hematopoietic stem cell transplantation

51%

Teshima T. , Matsuoka K. , Ichinohe T.

Archivum Immunologiae et Therapiae Experimentalis

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2006

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tom 54

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nr 3

165-172

EN

Allogeneic hematopoietic stem cell transplantation (HSCT) is known to cure various hematological disorders; however, its widespread use is limited due to a lack of histocompatible donors. Reciprocal cell traffic between the mother and fetus during pregnancy gives rise to postpartum fetal-maternal lymphohematopoietic microchimerism, which is frequently detected in the blood or tissue of healthy individuals. Studies in clinical and experimental transplantation provide evidence that exposure to non-inherited maternal antigens (NIMAs) during pregnancy may result in long-lasting fetomaternal microchimerism and tolerance induction. Studies of HLA-mismatched HSCT have suggested a relatively lower incidence of severe graft-versus-host disease (GVHD) after transplantation from a NIMA-mismatched donor. Studies using a mouse model have also demonstrated a 'child-to-mother' bone marrow transplantation from an NIMA-exposed donor to reduce the morbidity and mortality of GVHD in an antigen-specific manner while preserving the graft-versus-leukemia effects and favoring the immune reconstitution, thus resulting in a marked improvement in outcome after HSCT. Prospective clinical studies are therefore warranted to confirm these beneficial effects of fetal-maternal tolerance in allogeneic HSCT.

9

Modulation of auxiliary signals to T cells as a mechanism to induce transplant tolerance

51%

Gorczynski R. M.

Archivum Immunologiae et Therapiae Experimentalis

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2005

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tom 53

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nr 2

91-101

EN

Advances in the treatment of transplant rejection, autoimmune disease, allergy, and other conditions of altered immunoregulation have come from our improved knowledge of the multi-faceted nature of lymphocyte activation, incorporating not merely antigen triggering of specific receptors, but a myriad of other accessory signals, all operating within a defined environmental (cytokine) milieu. The review below focuses on just one aspect of this, the ability to manipulate costimulatory signals, or regulatory signals, as a means to induce long-standing immune suppression. Emphasis is placed on the dominant suppression mediated following activation of any one of a number of regulatory signals as a potentially more rational approach to clinical therapy, as the redundancy in costimulatory signals suggests that blockade of any one of these may be unlikely to produce permanent unresponsiveness. The role of regulatory T cells, induced following antigen presentation in the presence of immunoregulatory signals, is also discussed.

10

T cell depleted haploidentical bone marrow transplantation for the treatment of children with severe combined immunodeficiency

51%

Smogorzewska E. M. , Brooks J. , Annett G. , Kapoor N. , Crooks G. M. , Kohn D. B. , Parkman R. , Weinberg K. I. , D. B. K.

Archivum Immunologiae et Therapiae Experimentalis

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2000

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tom 48

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nr 2

111-118

EN

Severe combined immunodeficiency (SCID) is fatal in early childhood if unrecognized and if not treated. The aim was to determine the efficacy of T cell depleted bone marrow transplantation (TCD BMT) in the treatment of children with SCID. Eleven children diagnosed with SCID received histocompatible related donor bone marrow transplantation ? HRD BMT (group I). Thirty seven children diagnosed with SCID who did not have histocompatible donors were treated with TCD haploidentical parental bone marrow transplantation (BMT) (group II). TCD was performed by in vitro soybean lectin agglutination followed by E-rosette depletion. Patients were longitudinally assessed for the presence and function of T and B lymphocytes. In group I all children survived. The mean age of children in this group at the time of HRD BMT was 15. 4 months. All surviving patients normalized their specific T cell function. Two out of 11 require treatment with intravenous immunoglobulin i. v. Ig. In group II 17 out of 37 (46%) children survived. At the time of TCD BMT the mean age of survivors was 7. 5 months, vs. 11. 4 months in patients who died. Death was caused most commonly by opportunistic infections, Epstein-Barr virus induced lymphoproliferative disease (EBV-LPD), and graft versus host disease (GvHD). Seventeen out of 17 surviving patients recovered normal numbers of CD3+ cells and antigen specific T cell function. Five out of 17 never recovered their B cell function and require i. v. Ig injections. Early diagnosis, prevention or treatment of opportunistic infections, and enhancement of immune recovery will be necessary to improve survival in patients with SCID treated with TCD BMT.

11

Bone marrow stromal cells in traumatic brain injury (TBI) therapy: true perspective or false hope?

51%

Opydo-Chanek M.

Acta Neurobiologiae Experimentalis

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2007

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tom 67

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nr 2

187-195

EN

Recent studies regard bone marrow stromal cells as a potential andidate for cellular therapy of traumatic brain injury and thus as an attractive alternative for embryonic and fetal stem cells. Numerous experiments indicate that bone marrow stromal cells play an important role in the repair of injured brain tissue and also support healing processes. Findings of in vitro and in vivo studies show that these cells have an ability to differentiate into cells of multiple tissues, including neurons and glial cells and to secrete an array of growth factors and cytokines, which have an influence on repair of damaged tissue. In addition, treatment of traumatic brain injury with bone marrow stromal cells promotes functional recovery of injured animals. Taking this into consideration, there is hope for using bone marrow stromal cells in brain injury therapy, which is very difficult because of specific events that occur in the pathological conditions. However, mechanisms responsible for the observed therapeutic potential of bone marrow stromal cells still remain unclear. The review presents achievements in studies on bone marrow stromal cells as a source of therapeutic benefits in treatment of traumatic brain injury and addresses the question of their possible future use in clinical trials.

12

Immunosuppressive agents and cytomegalovirus infection

51%

Tanaka K.

Archivum Immunologiae et Therapiae Experimentalis

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2003

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tom 51

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nr 3

179-184

EN

Cytomegalovirus (CMV) infection is the major infectious complication observed after organ transplantation. As rejection episodes always occur in allograft-transplanted recipients, various kinds of immunosuppressive agnets are used to control such rejection episodes. Among the commonly used immunosuppressive agents, anti-pan T cell monoclonal antibody (OKT3) is known to increase the risk of viral infections. A new immunological techniques have recently been developed to measure CMV-specific CD4 and CD8 cells by flowcytometry. Using the techniques, the high frequencies of specific CD4 and CD8 T cells have been shown to be required to survey the CMV (re)activation in the persistent/latent phase of CMV infection. An excessive T cell depletion by OKT would deplete such surveying T cells, thus resulting in the occurrence of CMV-associated diseases.

13

The problems in donor - recipient matching in kidney and bone marrow transplantation

51%

Nowakowska B.

Postępy Higieny i Medycyny Doświadczalnej

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1995

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tom 49

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nr 1

107-115

14

Evidence for an immunoregulatory role of OX2 with its counter ligand (OX2L) in the regulation of transplant rejection, fetal loss, autoimmunity and tumor growth

51%

Gorczynski R. M.

Archivum Immunologiae et Therapiae Experimentalis

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2001

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tom 49

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nr 4

303-310

EN

Transplantation has emerged as an effective treatment for patients with end-stage organ failure. Current regimens of non-specific immunosuppressive drug treatment, which are needed life-long to prevent graft rejection, have numerous adverse side effects and increase the risk of opportunistic infections and malignancy. A major goal is to develop immunotherapeutic protocols that achieve specific tolerance. Such protocols would decrease and eventually eliminate the reliance on non-specific drug therapy. We showed that portal vein (pv) delivery of donor antigen prolongs the survival of vascularized and non-vascularized allo- and xeno-grafts, and that increased graft survival is associated with altered cytokine production and augmented expression of the molecule OX2. This review documents further evidence for a more general immunoregulatory role for the interactions of OX2 and its ligand, OX2L.

15

Monitoring of cellular chimerism in patients after sex-mismatched bone marrow transplantation: technical report

51%

Jolkowska J. , Ladon D. , Wachowiak J. , Witt M.

Journal of Applied Genetics

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2000

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tom 41

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nr 3

209-212

EN

Numerous hematological diseases, in particular leukemias, can be treated successfully with allogeneic bone marrow transplantation (allo-BMT). Highly polymorphic microsatellite markers and X, Y-chromosome-specific sequences provide useful genetic markers for detection of complete or mixed chimerism in patients after allo-BMT. Chimerism can be monitored successfully using polymerase chain reaction technique (PCR) and cytogenetic analysis, especially fluorescent in situ hybridization (FISH). It is still unclear whether individuals with mixed chimerism after bone marrow transplantation have an increased risk of developing leukemic relapse or graft rejection. Molecular study of cellular chimerism can also be used for quantitative assessment of the amount of donor's cells in a recipient after bone marrow transplantation and for monitoring of minimal residual disease (MRD) or disease relapse. We report application of three different DNA-typing techniques: automated DNA sizing technology, fluorescent in situ hybridization and also Y-specific DNA probing for analysis of post-BMT chimerism in a case of sex-mismatched bone marrow transplantation. Key words: allo-BMT, chimerism, FISH, PCR.

16

Active vaccination after allogeneic bone marrow cell transplantation: a new option in the immunotherapy cancer?

51%

Zoller M. , Matzku S.

Archivum Immunologiae et Therapiae Experimentalis

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2002

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tom 50

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nr 3

197-224

EN

The concept of immunotherapy of cancer has been evoked more than a century ago by W. Coley. Yet, it is only recently that the state of knowledge allows for molecularly defined therapeutic approaches and much effort will still be required to place immunotherapy beside of surgery, chemotherapy and radiation as a forth option. In this review, we will strongly focus on two aspects: active therapeutic vaccination, because it is our belief that this approach will provide a major breakthrough and the potential efficacy of combining active vaccination with allogeneic bone marrow cell transplantation. It lately could be established in clinical trials that allogeneic bone marrow cell transplantation does not require myeloablative conditioning. Only non-myeloabaltive conditioning, which avoids the high toxicity of the conventional approach, allows the recruitment of elderly patients and patients in poor health condition. Concerning active vaccination protocols we will address the questions 1) what the targets (i.e. the antigens) of immunotherapeutic approaches could be; 2) how to achieve an optimal confrontation of the immune system with these tumor-associated antigens; and 3) which response elements are needed for raising a therapeutically successful immune reaction against these. Many question remain to be answered in the field of allogeneic bone marrow transplantation after non-myelablative conditioning to optimize the therapeutic setting for this likely very powerfull tool of cancer therapy. We will briefly summarize current considerations to improve engraftment, to reduce graft versus host disease while strengthening graft versus tumor reactivity. There is some hope that the latter can be 'naturally' maintained during the process of T cell maturation in the allogeneic host. Provided this hypothesis can be substantiated, the efficacy of active vaccination of the allogeneically reconstituted host will meet a pool of virgin T cells, which are tolerant towards the host, but not anergized towards tumor antigens presented by MHC molecules of the host. We only briefly will mention suportive regimen of immunomodulation and those hazards which one is most frequently confronted with in trials to attack tumors with the inherent weapon of immune defense. Though successful immunotherapy of cancer still remains far behind expectation, there is a solid basis to believe that by improving our understanding of molecular mechanisms of immunity, it may become a very powerful and less harmful tool than conventional therapies.

17

No recovery of T-cell receptor excision circles (TRECs) after non-myeloablative allogeneic hematopoietic stem cell transplantation is correlated with the onset of GvHD

51%

Przybylski G. K. , Kreuzer K.-A. , Siegert W. , Schmidt C. A.

Journal of Applied Genetics

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2007

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tom 48

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nr 4

397-404

EN

Improper T-cell reconstitution with its consequences, graft-vs-host disease (GvHD) and outbreak of viral infections, is the major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). To determine the factors affecting reconstitution of naive T-cells after non-myeloablative HSCT (NM-HSCT), the T-cell receptor excision circle (TREC) content was measured on a weekly basis in 24 transplanted patients with various malignant diseases. We analysed correlations of the results with the development of GvHD. In addition, in 11 chronic myeloid leukaemia (CML) patients, we correlated TREC and BCR-ABL transcript numbers. After HSCT, in most patients (22/24) TRECs became undetectable. In 12 patients, TRECs reappeared 3?4 months after HSCT, in 1 patient TRECs reappeared 5 months after HSCT, and in 11 patients TRECs remained negative for more than a year. All 11 patients who remained TREC-negative, developed acute GvHD grade 2?3, while only 6 out of 13 patients who recovered TRECs developed GvHD. We show that after non-myeloablative HSCT, thymopoiesis takes place and is affected by GvHD. Our results indicate that no recovery of TRECs after NM-HSCT (which most likely reflect the expansion of host-reactive co-transplanted mature T-cells) correlates with the onset of GvHD.

18

Hematopoietic cell transplantation for chronic myeloproliferative disorders

44%

Tse W. , Deeg H. J.

Archivum Immunologiae et Therapiae Experimentalis

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2006

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tom 54

|

nr 6

375-380

EN

Myeloproliferative disorders, including chronic idiopathic myelofibrosis (CIMF), polycythemia vera (PV), essential thrombocythemia (ET), and chronic myelomonocytic leukemia (CMML), are clonal diseases of hematopoietic stem or precursor cells. They often show a protracted or chronic course; however, all have the potential of progressing to severe marrow failure, associated with myelofibrosis, or of transforming into acute leukemia. At that point, hematopoietic cell transplantation (HCT) is the only current treatment strategy with curative potential. If transplantation is being considered and a suitable donor is available, HCT should be carried out before leukemic transformation has occurred, as the success rate of HCT declines steeply in patients who have evolved to leukemia. As many as 75?80% of patients with the original diagnoses of PV or ET, about 65?70% with CIMF, and 45% of patients with CMML are surviving long term after allogeneic HCT using conventional transplant regimens, with follow-up now extending to 15 years. Results with HLA-identical related and unrelated donors are comparable. Major risk factors for the outcome after HCT are the disease stage, the presence of comorbid conditions, and patient age. The development of reduced-intensity conditioning regimens has allowed for successful HCT even for older patients and patients with comorbid conditions. Studies on disease mechanisms, including the recent characterization of an activating mutation in JAK2, may provide additional prognostic guidance and are likely to lead to the development of novel treatment strategies, which will require continuous reassessment as to the optimum timing of HCT.

19

Polymorphisms within the genes encoding TNF-alpha and TNF-beta associate with the incidence of post-transplant complications in recipients of allogeneic hematopoietic stem cell transplants

44%

Bogunia-Kubik K.

Archivum Immunologiae et Therapiae Experimentalis

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2004

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tom 52

|

nr 4

240-249

EN

Hematopoietic stem cell transplantation (HSCT) is a curative treatment of many hematological disorders. Recent studies have shown the associations between polymorphic features of cytokine-encoding genes and the incidence of post-transplant complications in the recipients of allogeneic HSCT. This review focuses on the relationship between the polymorphic patterns of patient genes encoding tumor necrosis factor (TNF)-alpha and TNF-beta and the manifestation of post-transplant complications, acute graft-versus-host disease (aGvHD), generation of toxic lesions, and mortality. Discussed in more detail are the relationships of TNFd microsatellites and polymorphisms within the promoter region of the TNF-alpha-encoding gene (TNFA) in the position (?308) and within the first intron of the TNF-beta-encoding gene (TNFB). It appeared that heterozygosity within the TNFA promoter and the first intron of the TNFB gene increased the susceptibility to severe grades III?IV of toxic complications, while the presence of the TNFd3 homozygous genotype was associated with a higher risk of severe aGvHD and early mortality in patients after allogeneic HSCT. These results imply that donor-recipient genotyping, extended to cytokine loci, may be of prognostic value for transplantation outcome.

20

Simultaneous transplantation of two allogeneic units of cord blood in an adult patient with acute myeloblastic leukemia. A case report

44%

Wiktor-Jedrzejczak W. , Rokicka M. , Urbanowska E. , Torosian T. , Graczyk-Pol E. , Tomaszewska A. , Krol M. , Paluszewska M. , Gronkowska A. , Ziarkiewicz-Wroblewska B. , Jolkowska J. , Witt M.

Archivum Immunologiae et Therapiae Experimentalis

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2005

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tom 53

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nr 4

364-368

EN

The major obstacle to the therapeutic use of hematopoietic transplantation is the unavailability of matched, unrelated marrow donors for the large number of potential patients, although all of them have the chance to find sufficiently matched, unrelated cord blood units. However, the use of cord blood as a source of cells for transplantation is limited by its cell number, usually below 1 billion, which allows for routine transplantation only in children weighting less than 30 kg, while most potential recipients possess a higher body mass. This led to the idea of the simultaneous use of several units of cord blood which, combined, would fulfill the requirements for the necessary cell number for an adult recipient. We attempted to simultaneously transplant an adult patient with refractory acute myeloblastic leukemia utilizing two different cord blood units, one fully matched and one mismatched at one locus. The patient became reconstituted with only one unit, the mismatched, as determined using microsatellite markers, and had no signs of relapse of leukemia. Unfortunately, he died of persistent fungal (brain aspergilloma) infection on day +103. The successful engraftment may suggest that a method based on the principle of using more than one cord blood unit for transplantation is feasible in large adult patients and may reach routine application.