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At least 19 recordsLinked to original sources
PubMed2003

Serum stem cell growth factor for monitoring hematopoietic recovery following stem cell transplantation.

Stem cell growth factor (SCGF) is a novel cytokine for primitive hematopoietic progenitor cells. Although it has burst-promoting activity and granulocyte/macrophage colony-promoting activity in vitro, its significance in hematopoiesis in vivo has not been elucidated. In this study, we have established enzyme-linked immunosorbent assay (ELISA) to quantify human SCGF and measured serum cytokines in normal volunteers and 27 patients undergoing stem cell transplantation (SCT), including six autologous and 21 allogeneic transplants. SCGF levels gradually increased after SCT regardless of graft-versus-host disease or type of transplant. The maximum level of SCGF was observed during the rapid granulocyte recovery phase in patients subjected to an autologous transplantation, and during the granulocyte stabilization phase in allogeneic patients. SCGF levels in PBSCT patients began to rise earlier than in BMT patients. Two patients with no increment of SCGF after SCT showed delayed engraftment. The source of SCGF was further analyzed by RT-PCR and we found that SCGF was highly expressed in bone marrow (BM) CD34(+) and CD34(-)CD33(+) cells, but not in BM CD34(-)CD33(-) cells, BM stromal cells and peripheral blood cells. The cell population expressing SCGF in BM possess the colony-forming cell activity. Therefore, serum SCGF can be an indicator of hematopoietic recovery following SCT.

Adolescent↗
PubMed2000

New approaches to treating malignances with stem cell transplantation.

Stem cell transplantation has been successfully used to treat a wide variety of hematologic malignancies. New and exciting strategies being developed for use in conjunction with transplant will be useful in overcoming tumor resistance. It is now clear that a significant part of the antitumor effect of allogeneic stem cell transplantation is derived from the graft itself and is independent of the preparative regimen. Immune therapy derived from the donor's graft is uniquely suited for killing chemoresistant tumor cells and may prove to be an invaluable tool for decreasing the risk of relapse in patients with advanced disease. Among patients who have relapsed after allogeneic bone marrow transplantation (BMT), an immunologically based antitumor effect may be obtained simply by transfusing T cells obtained by leukopheresis of the original bone marrow donor. Referred to as donor leukocyte infusion (DLI), this technique has been used to obtain complete remissions in relapsed acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), multiple myeloma, non-Hodgkin's lymphoma, myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). Another approach that uses the donor's graft to obtain a potent antitumor effect is the combination of nonmyeloablative BMT followed by immunotherapy with DLI. Numerous investigators are exploring ways of combining autologous BMT with immune therapy. Animal studies using tumor vaccines in conjunction with autologous transplantation offer a promising method for eliminating tumor. Patients undergoing autologous transplantation may have marrow that has been contaminated with tumor, which places them at a higher risk of relapse. Attempts have been made to eliminate contaminating tumor from the marrow by purging.

Bone Marrow Purging↗
PubMed2001

A randomized phase II study of amifostine used as stem cell protectant in non-hodgkin lymphoma patients receiving cisplatin-based salvage chemotherapy prior to stem cell transplant.

Stem cell mobilization may be inadequate in many lymphoma patients in need for autologous stem cell transplant (SCT). In this study, we sought to evaluate a potential role of amifostine as a stem cell chemoprotective agent in lymphoma patients receiving DHAP chemotherapy in preparation for high-dose chemotherapy (HDC) and stem cell transplant (SCT). In the beginning of the DHAP course, patients were randomized 1:1 to receive amifostine at 740 mg/m(2). Stem cells were mobilized with GCSF after the last cycle of DHAP. Stem cell collection started upon ANC recovery over 1000/mm(3). Standard 10 lt. apheresis daily with a goal of a minimum of 2 x 10(6) stem cells/kg were performed. Twenty-one patients have been enrolled; 10 received amifostine pretreatment (age, 20-64) and 11 were randomized to the control arm (age, 18-63). Prior chemotherapy was balanced in the two groups. The median number of DHAP treatments for each group was 2. Amifostine was well tolerated and was associated with higher stem cell collection. Toxicity and time to engraftment were comparable between the two groups. Our preliminary results may suggest a role of amifostine in protecting stem cells during salvage chemotherapy, thus facilitating stem cell collection.

Adolescent↗
PubMedDate not supplied

Stem cells and stem cell transplantation.

Stem cell transplantation (SCT) is an increasingly used therapeutic approach for the treatment of hematological and non-hematological disease of neoplastic and non-neoplastic origin. How the phenomena controlling blood cell production take place during SCT is still largely unclear. Increasing knowledge of stem cell biology, the availability of large amounts of stem cells due to mobilization techniques, as well as new developments in hematopoietic cell manipulation offer exciting experimental and therapeutical options in the field of SCT and will be reviewed here.

Colony-Forming Units Assay↗
PubMed1998

Bone Marrow Donors Worldwide and cord blood stem cell transplantation.

Stem cell transplantation using cord blood donors mismatched for one or two HLA antigens can be successful. A simulation study was performed to assess the percentage of patients for whom a matched and/or a one or two antigen mismatched donor is available. Using either bone marrow donors worldwide (BMDW) (n = 925109) or the cord blood donor file in BMDW (n = 11049). As a donor source, for 97% of the Dutch patients a 0 or 1 antigen mismatched cord blood donor was available, for patients from the minority groups this percentage was 55%. These percentages compare favourably with the fraction of 0 mismatched donors found in BMDW.

Blood Banks↗
PubMed2004

Current indications for reduced-intensity allogeneic stem cell transplantation.

Stem cell transplantation preceded by reduced-intensity conditioning (RIC) is based on the use of immunosuppressive agents as the sine qua non to ensure donor cell engraftment. It is a curative option for select patients suffering from haematological and non-haematological malignancies. The most beneficial results are observed when a full donor engraftment is achieved with 'tolerable' graft-vs-host disease (GVHD). To date, a vast amount of clinical data has been published, but in an uncontrolled manner. This review summarizes the currently known outcome of allogeneic transplants with RIC, with every disease category analysed separately. Unresolved problems include the optimal combination of immunosuppressive agents, the degree of infectious complications, and GVHD that may appear in some patients. Directions to overcome these complications are discussed. Despite the paucity of controlled clinical data, the current indications for RIC allogeneic transplantation are summarized based on the best-available phase II data.

Hematologic Neoplasms↗
PubMed2005

Non-infectious manifestations of stem cell transplantation.

Stem cell transplantation (SCT) is now commonplace within medical practice. With growth in transplant activities, outcomes are likely to continue to improve. Increasing numbers of the population now face life after transplantation. The aetiology of post transplant complications is multifactorial. Background knowledge of SCT and common, radiographically detectable, non-infective complications are important in everyday clinical practice. A review of these complications using a variety of imaging modalities is presented and the process of SCT briefly described. Tumour recurrence is outside the remit of this review.

Digestive System Diseases↗
PubMed2003

End-stage renal disease after high-dose carboplatinum in preparation of autologous stem cell transplantation.

Stem cell transplantation is one therapy employed in the management of children with high-risk solid tumors. However, this therapy is not without risk, having been associated with multiple end-organ toxicities. Both acute renal failure and chronic renal insufficiency have been reported in marrow transplant recipients, primarily in the context of the use of calcineurin inhibitors and radiation therapy. This report reviews our experience in managing an adolescent with metastatic Ewing's sarcoma who developed rapid progression to end-stage renal disease following a pretransplant conditioning regimen with high-dose carboplatinum. She had not received radiation or prior cisplatinum therapy. The possible reasons for the patient's highly unusual course and recommendations on ways to prevent this complication are discussed.

Adolescent↗
PubMed2004

Psychosocial adjustment and quality of life among multiple myeloma patients undergoing evaluation for autologous stem cell transplantation.

Stem cell transplantation has assumed a prominent place in the treatment of multiple myeloma, but relative to patients with other malignancies there is surprisingly little information about the adjustment difficulties and quality-of-life changes that these patients experience. This study examined psychosocial and functional deficits among myeloma patients assessed at a uniform period during their initial diagnostic evaluation, prior to beginning protocols at a transplant center. Validated self-report measures and clinician rating scales were used to assess 213 patients. Outcomes evaluated included emotional distress (Hospital Anxiety and Depression Scale, Brief Symptom Inventory), depression (Hamilton Depression Rating Scale), physical functioning, pain, and energy (SF-12). A significant proportion of patients experienced compromised psychosocial and physical functioning. Roughly one-third reported clinically elevated levels of distress, anxiety, and depression. In all, 59% scored below age-adjusted norms for daily physical functioning, 58% reported at least moderate levels of pain, and over 80% noted at least moderate fatigue. Clinical and demographic correlates of these outcomes were examined. These findings are among the first to characterize quality-of-life outcomes among myeloma patients in the transplant setting, and indicate that many patients experience considerable supportive care needs even prior to beginning aggressive regimens. Results highlight the importance of early screening.

Adaptation, Psychological↗
PubMed2004

[Thrombotic microangiopathy following stem cell transplantation].

Stem cell transplantation associated microangiopathy (TA-TMA) occurs in about 7% of all transplantations. While it resembles in all its features idiopathic TTP or HUS, response to plasma therapy is poor. The overall mortality of patients afflicted with TA-TMA is about 80%. Comparative studies aimed at discovering risk factors for the development of TA-TMA and defined different entities according to clinical, laboratory and outcome parameters. It is thought to be of multifactorial aetiology with the central event of endothelial damage. Intensive chemotherapy and radiation for bmt-preparation, infection in the immunocompromised host and graft versus host disease in conjunction with immunosuppressive therapy i. e. cyclosporine turn the haemostatic balance into a procoagulant state. Therapeutic strategies deduced from idiopathic TTP were disappointing with the only consensus in the withdrawal of cyclosporine from TA-TMA patients. Future trials are directed to ameliorate endothelial dysfunction.

Diagnosis, Differential↗
PubMed2004

Clinical implications of T cell receptor repertoire analysis after allogeneic stem cell transplantation.

Stem cell transplantation (SCT) constitutes a major challenge to the immune system. Long-term impairment of immunity against various common infectious stimuli leads to increased susceptibility to infectious diseases; in contrast, an immune response against the recipient may cause the devastating graft-versus-host disease (GvHD). Recovery of the immune system (both qualitative and quantitative) after SCT is perhaps the most important factor in determining the clinical outcome. Consequently, immune reconstitution has been extensively studied using different approaches, including quantitative analysis of immune cells as well as their phenotypic characterization. Analysis of diversity and clonality is an important tool in determining competence of the immune system, assuming that a broad diversity assures efficient response to different stimuli and clonal dominance reflects ongoing, potentially relevant immune responses. Detailed analysis of the immune repertoire through the flow cytometric and molecular study of the T cell receptor repertoire has been applied to gain quantitative and qualitative insights about the T cell immune competence and responsiveness. After SCT, a contraction of the T cell pool and a reduction in T cell receptor diversity is clearly associated with clinical immunodeficiency. Reconstitution of the immune system is often characterized by dominance of oligoclonal T cell populations, reflecting specific antigen-driven immune responses. Detailed characterization of T lymphocytes by T cell receptor analysis is possible, and may lead to the identification of individual clones involved in specific immune reactions, such as alloresponses in GvHD, the closely related graft-versus-leukemia effect and opportunistic viral agents such as CMV or EBV.

Graft vs Host Disease↗
PubMed2006

Role of platelet-derived chemokines (RANTES and ENA-78) after stem cell transplantation.

Stem cell transplantation (SCT) is being used for hematopoietic reconstitution following high-dose chemotherapy for malignancy. Some patients seem to have an imbalance of the immune response after SCT and cytokines are known to regulate this response. Recently, platelets have been shown to contain members of the chemokine family, suggesting a role of platelets as inflammatory cells. We measured and compared levels of platelet activation markers, chemokines, and soluble factors in patients undergoing SCT. IL-8 and GROalpha exhibited a significant elevation in the early phase (1 or 2 weeks) after SCT; this trend was marked after autologous SCT. Furthermore, these levels significantly and positively correlated with the change in G-CSF. In contrast, ENA-78 exhibited a significant elevation in the later phase (3 or 4 weeks) after SCT. In addition, its level negatively correlated with the change in G-CSF. Soluble CD40 ligand and platelet-derived microparticles significantly increased after both auto- and allo-SCT. In addition, ENA-78 positively correlated with the level of platelet-derived microparticles. The increase of RANTES seems to be related to platelet activation, since RANTES was in the dynamic phase similar to soluble CD40 ligand and platelet-derived microparticles. RANTES exhibited changes similar to IL-6, TNFalpha, and soluble IL-2 receptors, which are GVHD markers. Thus, the platelet-derived chemokines ENA-78 and RANTES exhibited particular changes after SCT. Our results suggest that ENA-78 play a role in hematopoietic conditions in which G-CSF is not involved, and RANTES generation after allo-SCT relates to GVHD.

Blood Platelets↗
PubMed2006

Transcriptional profiling of reporter genes used for molecular imaging of embryonic stem cell transplantation.

Stem cell therapy offers exciting promise for treatment of ischemic heart disease. Recent advances in molecular imaging techniques now allow investigators to monitor cell fate noninvasively and repetitively. Here we examine the effects of a triple-fusion reporter gene on embryonic stem (ES) cell transcriptional profiles. Murine ES cells were stably transfected with a self-inactivating lentiviral vector carrying a triple-fusion (TF) construct consisting of fluorescence, bioluminescence, and positron emission tomography (PET) reporter genes. Fluorescence-activated cell sorting (FACS) analysis allowed isolation of stably transfected populations. Microarray studies comparing gene expression in nontransduced control ES cells vs. stably transduced ES cells expressing triple fusion (ES-TF) revealed some increases in transcriptional variability. Annotation analysis showed that ES-TF cells downregulated cell cycling, cell death, and protein and nucleic acid metabolism genes while upregulating homeostatic and anti-apoptosis genes. Despite these transcriptional changes, expression of the TF reporter gene had no significant effects on ES cell viability, proliferation, and differentiation capability. Importantly, transplantation studies in murine myocardium demonstrated the feasibility of tracking ES-TF cells in living subjects using bioluminescence and PET imaging. Taken together, this is the first study to analyze in detail the effects of reporter genes on molecular imaging of ES cells.

Animals↗
PubMed2005

Transplanting stem cells: potential targets for immune attack. Modulating the immune response against embryonic stem cell transplantation.

The curative promise of stem cells and their descendants for tissue regeneration and repair is currently the subject of an intense research effort worldwide. If it proves feasible to differentiate stem cells into specific tissues reliably and safely, this approach will be invaluable in the treatment of diseases that lead to organ degeneration or failure, providing an alternative or supplementary source of tissue for transplantation. Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of a pre-implantation blastocyst that can produce all cells and tissues of the foetus. In recent years, several laboratories have described the directed differentiation of ES cells into multiple mature cell types including: cardiomyocytes; haemopoietic cells; hepatocytes; neurones; muscle cells and both endocrine and exocrine cells of the pancreas. How the immune system of the host will respond when these ES cell-derived mature cells are transplanted is ill defined. This review will focus on the potential mechanisms that the immune system could use to target ES cell-derived transplants and how unwanted responses might be prevented.

Animals↗