"Autologous Transplantation of Primordial Hematopoietic Cells"

Abstract

Hematopoietic stem cells (HSCs) are precursor, undifferentiated cells, which through proliferation, differentiation and maturation give rise to all cells of the hematopoietic and immune systems. HSCs are located at specific locations within the bone marrow (BM) and at rest only a small number circulate in the peripheral blood. However, in special situations, the bonds between the HSCs and the niches are broken, resulting in their excessive increase in peripheral blood (mobilization) in order to collect them for medical purposes. However, the mechanisms of mobilization include complex signaling pathways, molecules and cells, which do not act autonomously but complementary. The G-CSF granulocyte growth factor is used to mobilize and collect HSCs with or without previous chemotherapy, and their adequacy is determined by measuring the absolute number of CD34 + cells in the graft.However, there are patients who are unable to collect a satisfactory collection of CD34 + cells, so they take a CXCR4 receptor antagonist, plerixafor, achieving the minimum acceptable collection limit. Megatherapy (M / T) with high doses of melphalan accompanied by HSCs  is the treatment of choice for patients <65 years of age newly diagnosed with Multiple Myeloma. The most reliable attack schemes are the combinations of VCD mod and VTD. However, in the age of modern biological agents it has not been clarified whether autologous transplantation should be part of initial treatment or rescue therapy. AL-amyloidosis, Waldenstrom's macroglobulinemia, and POEMS syndrome are three rare diseases with a wide range of clinical manifestations. In AL-amyloidosis, long-term remission is achieved and in about half of the patients the affected tissues are restored.In POEMS syndrome, autologous transplantation has a particularly positive effect as 70% of patients have a haematological and clinical response with a 5-year remission without recurrence. In contrast, Waldenstrom's macroglobulinemia has limited data, and those who may benefit from autologous transplantation are those who are chemosensitive and those who are not.Hodgkin's lymphoma, neuroblastoma, Ewing sarcoma, Central Nervous system and genital tumors have been reported positively. Appropriate studies are already being designed and newer therapeutic agents are being incorporated, which will reduce the toxicity of the treatment and give increased effectiveness and survival to pediatric patients.Chemo-resistant patients have very limited chances of healing with megatherapy / autologous transplantationIn diffuse large B-cell lymphomas, PMLBCL and PCNSL, megatherapy / autologous transplantation treats the primary refractory or recurrent disease, while the chances of cure for chemo-resistant patients are zero. The incorporation of new targeting agents may improve the outcome of this process. In acute leukemia’s, which are catastrophic haematological diseases that occur throughout the age range of the population, a significant proportion of patients who initially respond to treatment will relapse later.The therapeutic protocol for establishing the initial response includes intensive chemotherapy and autologous transplantation. Although there is evidence for the usefulness of autologous transplantation of HSCs, clearly more data are needed to clearly determine the percentage of positive impact on these diseases.In recent decades, despite the great advances that have been made in the treatment and survival of children with malignancies, subcategories of patients with severe prognosis and increased recurrence rates remain. Autologous transplantation has been used to try to treat cancer cells that are resistant to cancer. Hodgkin's lymphoma, neuroblastoma, Ewing sarcoma, Central Nervous system and genital tumors have been reported positively.Appropriate studies are already being designed and newer therapeutic agents are being incorporated, which will reduce the toxicity of the treatment and give increased effectiveness and survival to pediatric patients. Autoimmune diseases, especially the most serious forms, are treated with severe immunosuppressive therapy and AMAAK with the aim of introducing fundamental immune changes in the structure of the immune system and the synthesis of lymphocytes that do not induce autoimmunity.A key point in the success of the transplant and the reduction of the mortality from the transplant is here again the appropriate choice of the patient with specific criteria per disease, as they are formed by the EBMT and ADWP and after a thorough control of their vital organs.. Bone marrow MSCs are pluripotent progenitor cells that have the ability to self-renew and differentiate into bone, fat and cartilage. They also have excellent immunosuppressive properties and reduced immunogenicity. Their excellent characteristics combined with their easy isolation from ΒΜ and their rapid proliferative capacity in vitro, have led to a number of clinical applications of regenerative medicine / tissue engineering as well as hematopoietic cell transplantation. However, more data are needed on their long-term safety. The application of HSCs in the field of cardiovascular diseases has emerged as a very promising therapeutic approach that extends the benefits of modern medication and reperfusion techniques. The main indications for autologous transplantation in cardiovascular disease are: acute myocardial infarction, ischemic and dilated cardiomyopathy. The results of clinical studies showed efficacy in reducing the size of the infarction and improved wall contraction. HSCs are administered by cardiac catheterization without the need for general anesthesia. Gene Therapy (GT) for genetic diseases of the blood aims at the genetic modification of HSCs and the lifelong production of differentiated cells with a normal phenotype. G /T has been successfully applied in primary deficiencies, β-Mediterranean anemia and hemophilia. Modern research focuses on further increasing security levels, such as rebuilding vectors, to reduce the chance of oncogenic being activated.

TORIS Spiridon