الفهرس يوجد فقط 14 صفحة متاحة للعرض العام
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المستخلص
A stem cell is the “mother cell” that leads to production of all various types of cells. A fundamental character of stem cells is the lasting ability to multiply when called upon to differentiate into specialized cells that can no longer divide.
Mature blood cells have a limited life-span and are continuously replaced by the proliferation and differentiation of a very small population of pluripotent hematopoietic stem cell (HSC) found primarily in bone marrow. In clinical medicine, this property has been employed to reconstitute the diseased hematopoietic system with a healthy one by performing HSC transplantation.
The description of HSC character has been largely a reflection of the used methods, techniques and hardware. CD34 is the most common marker used to obtain enriched populations of human HSC for clinical use. The majority of human cells capable of producing multi-lineage hematopoietic engraftment express CD34. CD34+ cells count above 2.5x106/kg BW predicts rapid, complete, sustained engraftment. Enumeration of CD34+ cells in graft, although useful, does not always predict the frequency, viability, and hematopoietic potential of the hematopoietic stem cells, especially after cryopreservation.
There is a lack of easy, accessible and optimal assays for HSC. All of the assays measure some aspect of HSC activity and identify cells with one or more HSC attributes. The only conclusive assay for true HSC remains the long term repopulation of bone marrow in conditioned recipients. Functional assays can be divided into in vivo and in vitro assays. The in vitro assays can be divided into long-term cultures and colony assays.
Depending upon the donor, the transplantation is called allogeneic, autologous or syngeneic. In each case, the source of these hematopoietic stem cells could be the bone marrow, peripheral blood or umbilical cord blood.
The ability of recombinant hematopoietic growth factors to mobilize blood cells, either alone or by enhancing chemotherapy mobilization increased the use of mobilized blood cells for transplantation.
The advantages of autologous transplantation include that there is no risk of graft rejection, no risk of incompatibility and no graft versus host disease. Problem areas of autologous transplantation include age limited, regimen related toxicity, graft failure, opportunistic infection, relapse, myelodysplasia, secondary malignancies, quality of life and cost/charge.
The advantages of PBPC mobilization include rapid and trilineage hematologic engraftment, more tolerable harvesting procedure (without general anesthesia), and less tumor contamination. The ability of autologous mobilized PBPC to provide long-term reconstitution, in comparison to marrow cells, leads to short hospital stay, low antibiotic courses and low transplantation cost.
The aim of autologous graft processing (BM or PB graft) is achieving graft, free from tumor cells without affecting the HSC function. This aim is achieved by concentrating and removing the tumor cell content of the graft. Graft processing is divided into simple and complex procedures. Purging is a technique used to remove tumor cell content of autologous graft before transplantation. Tumor purging can be improved with multistep strategies (positive-negative selection).
Autolgous graft is usually cryopreserved as the patient is not ready yet for transplantation. The graft is cryopreserved by using controlled rate programmable freezer.
Quality control mandates that each product should be assayed for sterility (aerobic/anaerobic bacterial and fungal culture are done at least once during processing), qualitative and quantitative cellular composition, and progenitor cell content (CD34+ count). Colony assays may also be employed to evaluate viability and functional activity of cells.
The success of autologous HSCT depends on extent of prior myelotoxic therapy, peripheral blood counts (pancytopenia, platelet count and CD34+ count), myelodesplasia on bone marrow examination, cytogenetic abnormality, source of hemopoietic stem cell and type of used mobilization regimen.
Recently, Autologous transplantation is generally used in hematopoietic and solid tumors to eliminate all malignant cells by administering high-dose chemotherapy with subsequent rescue of the patient’s bone marrow with previously collected autologous stem cells.
Autologous transplantation plays a limited role in AML and CML patients due to lack of graft versus host disease. It provides a new line of treatment in young patients with absence of cytogenietic abnormalities and absence of HLA identical donor.
The role of autologous transplantation in CLL and ALL is still under investigation. In MM, autologous transplantation has a limited palliative role. Autologous transplantation provides a new strategy option in patient with HL and NHL especially in those who failed to be treated with standard chemotherapy or in patients with early relapse.
The future of autologous transplantation can be exceptionally bright, especially considering recent new knowledge in the area of drug resistance, stem cell isolation, gene transfer, and post-transplantation immunotherapy (cytokines, monoclonal antibodies, vaccine) to overcome the problem of relapse.