Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By 2003, 97% autologous transplants and 65% of allogeneic transplants in Europe used mobilised peripheral blood stem cells (PBSC). Soon after their introduction in the early 1990's, PBSC were associated with faster haemopoietic recovery, fewer transfusions and antibiotic usage, and a shorter hospital stay. Furthermore, ease and convenience of PBSC collection made them more appealing than BM harvests. Improved survival has hitherto been demonstrated in patients with high risk AML and CML. However, the advantages of PBSC come at a price of a higher incidence of extensive chronic GVHD. In order to be present in the blood, stem cells undergo the process of "mobilisation" from their bone marrow habitat. Mobilisation, and its reciprocal process - homing - are regulated by a complex network of molecules on the surface of stem cells and stromal cells, and enzymes and cytokines released from granulocytes and osteoclasts. Knowledge of these mechanisms is beginning to be exploited for clinical purposes. In current practice, stem cell are mobilised by use of chemotherapy in conjunction with haemopoietic growth factors (HGF), or with HGF alone. Granulocyte colony stimulating factor has emerged as the single most important mobilising agent, due to its efficacy and a relative paucity of serious side effects. Over a decade of use in healthy donors has resulted in vast experience of optimal dosing and administration, and safety matters. PBSC harvesting can be performed on a variety of cell separators. Apheresis procedures are nowadays routine, but it is important to be well versed in the possible complications in order to avoid harm to the patient or donor. To ensure efficient collection, harvesting must begin when sufficient stem cells have been mobilised. A rapid, reliable, standardized blood test is essential to decide when to begin harvesting; currently, blood CD34+ cell counting by flow cytometry fulfils these criteria. Blood CD34+ cell counts strongly correlate with the apheresis yields. These are, in turn, predictive of the speed of haemopoietic recovery after transplantation, which has helped establish the adequate cell dose for transplantation. Following collection, PBSC may be transfused unmanipulated, processed to select specific cell subtypes, or stored for future use. Cryopreservation techniques allow long term storage of stem cells without significant loss of viability. Increasingly demanding calls for safety led to introduction of vapour phase storage, separate storage of infected material, and mandatory quality control measures at all stages of the cryopreservation process and subsequent thawing and transfusion. At the same time, safety of the personnel working in stem cell processing and storage laboratories is safeguarded by a set of regulations devised to minimize the risk of infection, injury or hypoxia. Requirements for quality and safety have been shaped into a number of documents and directives in Europe and USA, emphasising the importance of product traceability, reporting of adverse reactions, quality management systems (standard operating procedures, guidelines, training records, reporting mechanisms and records), requirements for cell reception, quarantine, process control, validation and storage. Establishments that collect, process and store stem cells must be accredited or licensed by appropriate national or international authorities on a regular basis. These regulatory measures have recently become law across the European Union.
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PMID:Harvesting, processing and inventory management of peripheral blood stem cells. 2193 28

Hematopoietic stem cell transplantation (HSCT) has evolved from a largely experimental therapeutic approach three decades ago to a well-established therapy today for many malignant and non-malignant disorders of the hematopoietic and the immune system. Although it is per se a therapy by transmission of cells, protein therapeutics such as growth factors and antibodies are relevant in all phases of a HSCT and substantially contribute to the success of this often only curative treatment. This review discusses HSCT with a particular focus on the protein therapeutics involved. Granulocyte colony stimulating factor (G-CSF) for mobilization of stem cells to the peripheral blood, the polyclonal anti-T-cell globulin (ATG) and the monoclonal antibodies alemtuzumab and etanercept for prophylaxis and therapy of graft versus host disease (GvHD) are highlighted. Also rituximab, palivizumab and polyclonal intravenous immunoglobulins for treating infections in post-transplant patients are discussed. Since our understanding of cell surface receptors, cytokine and signaling pathways is increasing, there will emerge new targets for directed therapy by proteins in the future. They may have the potential to further improve the success and to widen theapplication of HSCT.
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PMID:[Proteins support stem cells - use of protein therapeutics in hematopoietic stem cell transplantation]. 2204 26