Bone Marrow Transplantation and Donation - Essay Example

?Bone Marrow Transplantation and Donation The of Your Paper Bone Marrow Transplantation and Donation Social Security Number: Course Name, Number, and Section Number: Name of Instructor: Bone Marrow Transplantation and Donation Bone marrow transplantation has been described as a heroic management of some devastating diseases like leukemia, lymphomas and aplastic anemia (Scales, 2008). With years of research and improvement in procedure, this surgery has more hurdles to cross as significant morbidity has been associated with it still. Intensive care is needed by about 40% of patients. The complications requiring ICU care are respiratory or hepatic or neurological problems (Scales, 2008). ICU stay would usually be hectic with frequent monitoring, institution of mechanical ventilation, renal replacement therapy and continuous infusions. The conditions for doing bone marrow transplantations, selecting the donor if doing allogeneic transplants, the actual surgery, the prevention of immune suppression after the surgery and ensuring the survival of the patient have heightened the risk of the ominous event that is bone transplantation. This paper is exploring the biological features including the anatomy and physiology of bone transplantation investigated in the various researches. Initially the normal anatomy and physiology have been described so that the reader gets a better picture of what is intended by this research. Normal anatomy and physiology of bone marrow The soft tissue that lies in the spaces between the bone trabeculae of flat bones is bone marrow. Blood vessels, nervous tissue, phagocytes, stem cells and blood cells at different stages of maturation are found in the bone marrow (Elgazzar, 2004). The red marrow has hemopoietic cells which are active while the yellow marrow is mainly fat and hemopoietically inactive. The bone marrow is essential to the human life as it provides all the blood cells: red blood cells, white blood cells and the platelets. The manufacture of the blood cells depends on the needs of the body. Active bone marrow is found mostly in the flat bones of the vertebrae (28%), pelvis (34%), the cranium together with the mandible (13%), the ribs and the sternum, (10%) and the proximal ends of the femur and humerus (4%-8%) (Elgazzar, 2004). The manufacture of blood cells is termed hemopoiesis. It begins in the human body at the fourth month of the intra-uterine life of the fetus. Within two months it functions more than the liver in the hematopoietic action. By birth, the red bone marrow becomes fully responsible for the blood cell formation. The cartilaginous epiphyses which did not have the red bone marrow at birth soon had it in the first few months of life (Elgazzar, 2004). The adult bone has active red marrow in the various bones different proportions. The usual conversion of red marrow is to the yellow marrow. However in certain pathological conditions, the reverse process occurs. Alterations to the distribution of the red marrow could change in conditions which are traumatic to the human body like surgeries, trauma or infections or malignancy (Elgazzar, 2004). Immune response Lymphocytes were the natural killer (NK) cells which were significant role players in the immune responses, both innate and adaptive (Olson et al, 2009). Lymphocytes provided the response to virus attacks, microbes and some tumors. The NK cells were white blood cells produced in the bone marrow and then moved to the region of the spleen, liver, lung, blood and lymph nodes where they resided (Olson et al, 2009). The period of maturity from a bone cell precursor to maturity came to 28 days. When an attack from viruses or microbes or tumors occurred, signals reached the NK cells which then migrated to the sites of attack through the expression of inflammatory chemokine receptors by virtue of their homing behavior (Olson et al, 2009). At the key sites, the NK cells entered the lymphoid tissue in the lymph nodes and non-lymphoid tissue in the liver and lung. T cells had the property of proliferation at the periphery but mature NK cells did not. However homeostatic proliferation occurred in NK cells when in a “syngeneic lymphopenic environment” (Olson et al, 2009). Bone marrow transplantation When the bone marrow became damaged for some reason, the major function of producing blood cells essential for sustenance of life was disturbed. This was when bone marrow transplant was thought of. The replacement of diseased or damaged bone marrow with donated bone marrow which was functional was termed bone marrow transplantation (Smith et al, 2003). There were autologous and allogeneic transplants. Autologous transplants were the patient’s own bone marrow which had been collected when the patient was in a normal functioning state. The marrow would be collected or harvested, cryopreserved or frozen and then re-infused according to the regimen (Smith et al, 2003). This method of transplantation was possible only when the patient had sufficient stem cells in his bone marrow which could finally generate into the blood cells. Tumors which needed bone marrow suppressing chemotherapy or high doses of radiation could have remissions when the bone marrow became normal (Smith et al, 2003). The bone marrow was collected during the remission period and used during the relapse period. Patients with malignant lymphomas and breast cancer could use autologous transplants. Allogeneic transplants were obtained from another person. Suitable donors who were tissue-typed donated the bone marrow. This was usually done for treatment of malignant hematological diseases like leukemia and non-malignant diseases like aplastic anemia (Smith et al, 2003). Graft-Versus-Host-Disease occurred as a complication in bone marrow transplantation due to the tissue damage caused by the pre-transplant conditioning regimen (Olson et al, 2009). The damage triggered host cells causing the secretion of pro-inflammatory cytokines. The cytokines in turn activated the dendrites of the host cells and caused the pathophysiology of GVHD. Bone marrow transplantation was one situation where the NK cells were an essential cellular therapy to prevent immunosuppression. This was because graft-versus-host-disease (GVHD) was not caused by NK cells. Moreover the NK cells maintained the graft-versus-tumor further preventing the GVHD. This property of NK cells was especially useful in allogeneic BMT for patients with solid tumors and leukemia where evidence of efficacy had been obtained in some patients (Olson et al, 2009). Allogeneic BMT was essential if the donor was a haploidentical one. Another beneficial point was that donor NK cells promoted bone marrow engraftment in these cases. Allogeneic bone transplantation Immunosuppression was a significant complication of allogeneic bone transplantation even though the therapy provided a general increase in survival (Goldberg et al, 2009). The immunosuppression involved the T cell compartment severely and was the reason for opportunistic infections. These infections contributed to the morbidity and mortality after allogeneic bone transplants (Goldberg et al, 2009). The aging patient showed lesser recovery when compared to the young, the reason being attributed to the thymic atrophy and the resultant decrease in the naive T cells. Goldberg et al indicated that sex steroid ablation and chemical castration using leuprolide acetate caused a reconstitution of T cells after allogeneic bone marrow transplant (2009). The donor derived CD4+ and CD8+ cells were increased after allogeneic BMT coupled with chemical castration by leuprolide (Goldberg et al, 2009). The progenitors of hemopoiesis in the bone marrow, the thymocyte subsets and the splenic T cells were increased. The increase in the progenitor cells had no influence on the donor-derived myeloid cells but the donor derived B cells were increased. Withdrawal of sex steroids had indicated a rise in B cells in earlier researches (Goldberg, 2009). The conclusion was that the elevated T cell reconstitution resulted due to the increase of lymphoid precursors and thymic regeneration. Graft-versus-host-disease showed no exacerbation while the activity of Graft-versus-tumor was maintained (Goldberg et al, 2009). A problem in allogeneic BMT Alpdogan et al (2008) indicated that a problem existed in post-transplantation following allogeneic BMT. A delay in the healing process occurred which could be due to impaired thymopoiesis and delayed peripheral T cell reconstitution. The expression of CD44hi peripheral T cells which proliferated very fast and became apoptosed led to a delay in T cell reconstitution and lymphopenic recipients showed a speedy proliferation of nonalloreactive T cells. The study indicated that a higher quantity of apoptotic cells were found in two murine models, one of which had received a transplant and the other had not. Patients who had developed GVHD after transplantation had the thymopoiesis and T cell reconstitution highly suppressed (Alpdogan et al, 2008). The peripheral T cells of the donor bone marrow showed a greater level of apoptotic cells than the alloreactive T cells in the recipients with GVHD. Simultaneously there was a decrease in the antiapoptotic molecules Bcl-2 and Bcl-XL and so the two phenomena had been associated. It was found that peripheral T cell apoptosis could not be modulated by Fas deficiency, the CD8+ T cells which came via the TRAIL pathway or increased expression of Bcl-2 or Akt after allogenic BMT (Alpdogan et al, 2008). Bone marrow transplant in severe immunodeficiency Severe combined immunodeficiency was treated best by bone marrow transplantation from an HLA-identical donor sibling with no conditioning but immune reconstitution could be decreased for a long period (Cancrini et al, 2010). Two children from the same family with adenosine deaminase deficiency had bone marrow transplantations. The patient who was conditioned showed bone marrow cells and B cells of many lineages. More thymus-derived naive T cells and receptor excision circles were found. The T cell repertoire was also normal. Faster B cell and metabolic reconstitution were further noted (Cancrini et al, 2010). Both patients had no GVHD or major complications. The second patient who had an unsuccessful earlier transplant had been given a low intensity regimen. This patient showed some neutropenia for a short period but later recovered. After three years their follow-up showed a normal growth of both children (Cancrini et al, 2010). Future research could focus on having a reduced intensity in the study of HLA identical BMT for ADA deficiency. Infants who had been diagnosed early and having no organ damage could be taken up for research. Later patients with greater risk could be participants (Cancrini, 2010). Two sisters had severe combined immunodeficiency due to inherited identical haplotypes (Richard et al, 1996). One sister (A) had successful haploidentical bone marrow transplantation from their father. The second sister (B) later had a successful transplant from the first sister. This was an exceptional case as B cell engraftment did not occur here (Richard et al, 1996). Serum immunoglobulins also returned to normal. Patient B had an uneventful course post-transplant as the lymphocytes from Patient A were tolerated by the HLA antigens in Patient B. This had probably happened because T cells from the father had reconstituted the immune system of patient A (Richard et al, 1996). Patient A became positive for HLA-DR7. The father’s T cells in patient A could have been not responding to cells from an unrelated person with HLA-DR7 but the T cells from the father had been stimulated by cells from patient A. This non-reactivity was a phenomenon demonstrated by other researchers (Richard et al, 1996). . Summary Bone marrow transplantation became successful when the immune response in the body of the recipient was good. The natural killer cells, the lymphocytes, protected the body through an immune response by travelling to the site of attack by viruses, microbes, or tumors from their area of residence in the spleen, liver and lung, blood and lymph nodes (Olson et al, 2009). The replacement of diseased or damaged bone marrow with donated bone marrow which was functional was termed bone marrow transplantation (Smith et al, 2003). Autologous BMT used the patient’s own bone marrow which was collected or harvested, cryopreserved or frozen and then reinfused according to the regimen (Smith et al, 2003). This was possible when the patient was in remission during the treatment of malignancies and transplanted when the patient was in relapse. Allogeneic transplants were obtained from another person or a donor after tissue-typing. Graft-versus-host-disease was a complication of BMT caused by tissue damage which triggered the secretion of pro-inflammatory cytokines. Immunosuppression was a complication which involved the T cell compartment severely and was the reason for opportunistic infections which could end fatally. The activity of graft versus tumor was a favorable state which also prevented GVHD (Goldberg et al, 2009). Goldberg et al indicated that sex steroid ablation and chemical castration using leuprolide acetate caused a reconstitution of T cells after allogeneic bone marrow transplant causing a speedy recovery after BMT (2009). Impaired thymopoiesis and delayed peripheral T cell reconstitution caused a delay in healing (Alpdogan et al, 2008). The nonreactivity seen in a child with severe combined immunodeficiency who had a BMT from her haploidentical sister who already had been a recipient of BMT from their father was a notable study case (Richard et al, 1996). Severe combined immunodeficiency was treated best by bone marrow transplantation from an HLA-identical donor sibling with no conditioning but immune reconstitution could be decreased for a long period as an ill-effect (Cancrini et al, 2010). Future research could focus on having a reduced intensity in the study of HLA identical BMT for ADA deficiency. Infants who had been diagnosed early and having no organ damage could be taken up for research. Later patients with greater risk could be participants (Cancrini, 2010). References: Cancrini, C., Ferrua, F., Scarselli,A., Brigida, I., Romiti, M.L. and Barera, G. et al. Role of reduced intensity conditioning in T-cell and B-cell immune reconstitution after HLA-identical bone marrow transplantation in ADA-SCID. Haematologica 2010;95(10):1778-1782. doi:10.3324/haematol.2010.025098 Elgazzar, A.H. Orthopedic nuclear medicine Springer, 2004 – Medical Goldberg, G.L., King, C.G., Nejat, R.A., Suh,D.Y., Smith,O.M., Bretz, J.C. et al.. Luteinizing Hormone-Releasing Hormone Enhances T Cell Recovery following Allogeneic Bone Marrow Transplantation. J Immunol. 2009 May 1; 182(9): 5846–5854. doi:10.4049/jimmunol.0801458. Olson, J.A., Zeiser, R., Beilhack, A., Goldman, J.J. and negrin, R.S. Tissue-Specific Homing and Expansion of Donor NK Cells in Allogeneic Bone Marrow Transplantation J Immunol. 2009 September 1; 183(5): 3219–3228. doi:10.4049/jimmunol.0804268. Richard, S.E., Robert, R. L., Jean, H.-L., Wakim,M.E., et al. Bone marrow transplantation in severe combined immunodeficiency from a sibling who had received a paternal bone marrow transplant. The New England Journal of Medicine 335. 24 (Dec 12, 1996): 1811-4. Scales, D.C., Thiruchelvam, D., Kiss, A., Sibbald, W.J., Redelmeier, D.A. Intensive care outcomes in bone marrow transplant recipients: a population-based cohort analysis Critical Care 2008, 12:R77 (doi:10.1186/cc6923) Smith, M. C.; Reeder, F., Daniel, L.; Julaluk B.; Hagman, J. Outcomes of touch therapies during bone marrow transplant. J. Alternative Therapies in Health and Medicine 9. 1 (Jan/Feb 2003): 40-9. Alpdogan, S.O., Lu, S.X., Patel, N., McGoldrick, S., Suh,D., Budak-Alpdogan, T. et al. Rapidly proliferating CD44hi peripheral T cells undergo apoptosis and delay posttransplantation T-cell reconstitution after allogeneic bone marrow transplantation. Blood. 2008 December 1; 112(12): 4755–4764. Read More