Topic Related to Anatomy/Physiology Essay

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Bone marrow transplantation is a procedure in which healthy marrow tissue from an appropriate donor is transferred to the recipient, who has a diseased bone marrow that is not able to function properly[i].  They are procedures performed to restore the stem cells in the bone marrow that may have been destroyed by disease, may be unable to function normally or is seriously suppressed following chemotherapy and radiotherapy whilst treating different types of cancers in the body.  Bone marrow therapy may be required as a main form of treatment (e.g. in the case of leukemia or lymphoma) or as an adjuvant therapy (e.g. in the case of other cancers).

It may be required in several disorders including blood disorders, certain metabolic disorders, certain hereditary disorders, immune disorders and malignant disorders, etc.  The bone marrow may be derived from the individual itself before chemotherapy and radiotherapy is initiated (autograft), from another person known as a donor (allograft) or from an identical twin (syngeneic graft)[ii].

Some of the conditions in which bone marrow transplantation is required include thalassemia and sickle cell anemia (in which the red blood cell production is abnormal), malignancies of the blood or the related organs such as leukemias, lymphomas and myelomas, suppression of the bone marrow and the normal production of the blood cells (aplastic anemia), conditions in which the immune action gets compromised (such as congenital neutropenia and severe combined immunodeficiency syndrome), and conditions in which there seems to be an error occurring in the metabolism due to defects in the enzymes and the cell lines[iii].

Although, bone marrow transplantation has not been utilized as a routine or a standard form of treatment, it is frequently performed to successfully treat several cancers affecting the blood such as leukemia, lymphoma and myeloma, and also several immune deficiency disorders.  It has proved to be a cure and a hope for several people suffering from otherwise fatal disorders.  The entire process of bone marrow transplantation takes a very long-time, requires a lot of preparation and needs a comprehensive team of healthcare professionals and specialists.

Some of the specialists that may be required during the process includes oncologists, hematologists, immunologists, nurses, nurse coordinators, social workers, nutritionists, dentists, physical therapists, respiratory therapists, laboratory technicians, dermatologists, surgeons, anesthesiologists, gastroenterologists, psychologists, etc.  All patients suffering from cancers of the blood cannot be indicated for bone marrow transplantation.  The patients should be evaluated thoroughly for several criteria including age, general health, presence of an appropriate donor, severity of the disease, expected outcome of the disorder and the transplantation, use of medications, etc.  The risks and the benefits are carefully evaluated before the surgery[iv].

Before the bone marrow is performed, the tissues are thoroughly matched utilizing HLA tissue typing.  Only if a suitable donor is present and the outcome of the disorder seems to be favorable is bone marrow transplantation performed.  Both the recipient and the donor should be prepared thoroughly before the operation[v].  Some of the potential donors include siblings, twins, parents, relatives, non-relatives or distant relatives.  The donor needs to undergo several tests including HLA matching and blood tests and physical fitness tests to determine their ability to donate a bone marrow tissue for transplantation.  Genetic tests are also required to help in the determining the compatibility between the donors and the recipients bone marrow tissues.

The process of obtaining the bone marrow tissues for transplantation is very complex.  After administering a suitable anesthetic agent to make the individual comfortable with the procedure, a wide-bore needle is placed into the bone marrow present in the hipbones or the sternum region to obtain the tissues for transplantation[vi].  The donor may feel some amount of pain, soreness and tiredness for a few days once the marrow tissues are removed from the site.  It may take a few days for the bone marrow to replace these tissues and for the symptoms to get relieved.

  Before the bone marrow tissues is transplanted to the recipient, the blood cells and the blood is removed.  The bone marrow cells are preserved until transfer surgery by a process known as cryo-perservation (freezing)[vii].  The donation is timed in such a way that it corresponds to several factors such as the medical condition of the patient and the availability of the donor.  The donor may have to be hospitalized as a general anesthetic is required[viii].  About two pints of bone marrow tissue is usually taken from the donor[ix].




Before the transplanted tissues are administered to the individual, a thorough conditioning is required to ensure that the bone marrow tissues are accepted by the recipient and the tissues are able to function fully.  Chemotherapy along with radiotherapy is required to degenerate that defective bone marrow tissue in the recipient and prepare them to accept the bone marrow of the donor.  The bone marrow is usually administered into the peripheral blood, utilizing a thin specialized plastic tube known as the Hickmans tube, from where it enters the bone marrow space and harbors itself to produce blood cell and certain substances in the future[x].

The new bone marrow begins to produce blood cells within 3 to 4 months and function to their full extents within three to four years[xi].  After the bone marrow tissues have been injected, the indvidul requires supportive care in the form of prompt treatment of infections, anemia and bleeding episodes[xii].  Usually, the bone marrow tissues from younger individuals are preferred as they seem to be more potent in producing blood cells.  The individual should be prepared both mentally and physically to overcome the hardships that may occur during the period around the transplantation.

  The bone marrow transplantation team has a unique way of demonstrating the period around which bone marrow transplantation is performed[xiii].  The minus days are the days before the surgery, whereas the day of the transplant is known as day zero.  The period between surgery and the recovery is known as plus days.  The individual may experience several problems and complications in relation to the bone marrow transplantation process.  During the procedure, the individual may develop pain, allergic reactions, chest pain, fever, etc.  After the procedure the individual is at a risk of developing frequent infections, sore throat, excessive bleeding, anemia, tiredness, breathlessness, nausea, weakness, vomiting, diarrhea, ulcers in the mouth, mental problems, etc.  Some individuals may require hospitalization for extended periods, whereas others may require blood transfusions[xiv].

The complications that may develop following the blood transfusions vary depending on the type of marrow transplanted, the specific disorder treated, the general health and the age of the patient, and the extent of similar of the tissues between the recipient and the donor.  Some of the infections that may develop (bacterial, viral or fungal) may be life-threatening or even fatal.  Some of the most commonly seen infection includes herpes simplex, cytomegalovirus virus infections, varicella zoster infection, pneumocystis carinii, etc[xv].

Pain and inflammation may develop in several parts of the body.  The kidney is often insulted during the transplantation process and may result in fluid overload in the body.  This may be associated with the drugs, IV fluids, blood products and the nutrition.  The lungs are frequently involved with the changes that develop during the transplantation and could result in respiratory distress and breathing problems.  The other organ that may be affected with the use of drugs and radiation during the treatment includes the heart and the liver[xvi].

Graft versus host disease (GVHD) is serious condition often associated with death and fatal outcomes following transplantation of the bone marrow.  Mild forms of the disease can worsen the quality of life and severe forms can result in serious medical problems and may also cause fatal outcomes.  The T-cells present in the blood may get sensitized against the foreign tissues and cause their destruction.

It can occur in acute and chronic forms.  Acute GVHD can develop within a few days following insertion of the transplanted tissues and may involve the liver, gastro-intestinal system and the skin.  Usually, the problems that develop are infectious in nature.  Several chemotherapeutic agents and immunosuppressant such as methotrexate and cyclosporine have been utilized to treat acute GVHD.  Besides, corticosteroids are also administered to treat any severe symptoms[xvii].

Chronic GVHD is a condition that develops following acute GVHD or may develop independently.  In mild forms of the disease, the individual develops a skin rash, whereas in severe forms the individual develops a connective tissue disorder.  Corticosteroids and cyclosporine are usually given to treat chronic GVHD[xviii].

Frequently, in several chronic leukemias, bone marrow transplantation offers the only means by which the disease can be treated on a long-term basis.  The patients needs to be below the age of 40 years for the transplantation to be more successful and needs to have a suitable donor.  Leukemia patients should ideally be treated in the chronic phase as the chances of survival and even a cure are better.  If the transplantation is performed during the blast crisis or the accelerated phase, the chances of recovery are very poor indeed[xix].

Nowadays due to the limitations in bone marrow transplantation, researchers are increasing looking at the prospect of using unrelated donors.  However, the chances of complications and unfavorable outcomes (including fatal outcomes) are realistically higher with unrelated donors than histo-compatible donors.  The chances of long-term survival are only about 40 %[xx].

Bone marrow transplantation was utilized to treat breast but was found to be not so very beneficial.  A study was conducted to determine the effects between bone marrow transplantation along with chemotherapy and chemotherapy alone.  The effects on the bone marrow transplanted group were found to be no better than the other group[xxi].

In another study in two groups of individuals suffering from Hodgkins disease, the first group underwent Bone marrow transplantation along with chemotherapy and the second group underwent chemotherapy alone (individuals were in stage 2 to stage 4 of the disease).  After about 4 to 5 years, the results obtained between the bone marrow transplant plus chemotherapy group and the chemotherapy group was almost similar to each other.  The survival rate was about 68 % and the cure rate was about 61 %.  On the other hand, the survival rate of chemotherapy alone was about 77 % and the cure rate was about 56 %[xxii].  Thus it can be seen that bone marrow transplantation does not offer great benefits in treating Hodgkins lymphoma.

In another study, the risk of the individual developing unfavorable outcomes including the formation of solid cancers after treatment with bone marrow transplantation was assessed.  Of the 20, 000 patients who had received allogenic bone marrow transplants (about 97 %) and a smaller percent which received syngeneic transplants (3%), the risk of the individual developing solid cancers was relatively higher than the general population.

The individuals who survived for more than 10 years had a 8.3 % risk of developing solid cancers.  At 10 years, the risk 2.2 % and at 15 years the risk was about 6.7 %.  The risk of developing solid cancers was relatively higher in those who were younger.  Patients that had developed GVHD were at a higher risk of developing solid cancers especially squamous cell carcinoma of the mouth and the skin.  Individuals prepared with radiotherapy had a higher chance of developing cancers following bone marrow transplantation[xxiii].

The chances of the child developing dental decay as potential bacterial infections following bone marrow transplantation are very high.  The individuals immune system is compromised so as to reduce the risk of developing transplant rejections.  Before the bone marrow transplantation therapy could go on about 150 of the 259 patients who were a part of this study had dental problems especially dental caries.

Several factors that may be activated during the bone marrow treatment stages such as radiotherapy and the reduced salivary secretion may encourage caries rates.  There was an increase in the caries rate and incidence of bacterial infection of the teeth following bone marrow transplantation[xxiv].  Hence, it would be ideal that all dental treatments are completed before the bone marrow transplantation procedures are initiated.




 Looking and the effectiveness and safety of bone marrow transplantation, I do feel that the technique is still in the infancy stages and may not be effective in treating all forms of cancers.  In some conditions, bone marrow has provided a new hope for survival.  In other conditions, the chances of survival may be increased very slightly only.  The physicians and the hematologists should closely assess the chances of risks and the potential benefits that could develop following the surgery.

Several factors such as use of chemotherapy, severity of the patients condition, use of radiotherapy, general health and age of the patient, presence of a histo-compatible donor, etc, needs to be considered closely before the patient is chosen for bone marrow transplantation.  Each of these factors plays a major role on the prognosis and the survival rates.  For autologus transplants, the success rate is about 40 to 75 %, and in allogenic transplants, the success rate is 10 to 40 %.  The success rate is higher once the cancer present in the bone marrow has been eradicated[xxv].




 

 

 

[i] Matsui, W. Bone marrow transplant. Medline Plus. 2006. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/003009.htm Accessed May 9, 2007.







[ii] NCI. Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation: Questions and Answers. 2004. Available at: http://www.cancer.gov/cancertopics/factsheet/Therapy/bone-marrow-transplant Accessed May 9, 2007.







[iii] Mackie MJ, Ludlam CA. Diseases of the blood. In. Edwards CRW, Bouchier, IAD, Haslett, C, ed. Davidsons Principles and Practice of Medicine. Philadelphia: Churchill Livingstone; 1996: 808-812.







[iv] Stanford Comprehensive Cancer Center. Information about Blood Diseases: Bone Marrow Transplantation. 2006. Available at: http://cancer.stanford.edu/blood/leukemias/bmt/ Accessed May 9, 2007.







[v] Stanford Comprehensive Cancer Center. Information about Blood Diseases: Bone Marrow Transplantation. 2006. Available at: http://cancer.stanford.edu/blood/leukemias/bmt/ Accessed May 9, 2007.







[vi] Stanford Comprehensive Cancer Center. Information about Blood Diseases: Bone Marrow Transplantation. 2006. Available at: http://cancer.stanford.edu/blood/leukemias/bmt/ Accessed May 9, 2007.







[vii] NCI. Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation: Questions and Answers. 2004. Available at: http://www.cancer.gov/cancertopics/factsheet/Therapy/bone-marrow-transplant Accessed May 9, 2007.







[viii] Mayo Foundation for Medical Education and Research. Bone Marrow Transplant Process. 2007. Available at:  http://www.mayoclinic.org/bone-marrow-transplant/process.html Accessed May 9, 2007.







[ix] NHS-UK. Bone Marrow Transplant. 2006. Available at: http://www.nhsdirect.nhs.uk/articles/article.aspx?articleId=621 Accessed May 9, 2007.







[x] NHS-UK. Bone Marrow Transplant. 2006. Available at: http://www.nhsdirect.nhs.uk/articles/article.aspx?articleId=621 Accessed May 9, 2007.







[xi] Mackie MJ, Ludlam CA. Diseases of the blood. In. Edwards CRW, Bouchier, IAD, Haslett, C, ed. Davidsons Principles and Practice of Medicine. Philadelphia: Churchill Livingstone; 1996: 808-812.







[xii] Stanford Comprehensive Cancer Center. Information about Blood Diseases: Bone Marrow Transplantation. 2006. Available at: http://cancer.stanford.edu/blood/leukemias/bmt/ Accessed May 9, 2007.







[xiii] Mackie MJ, Ludlam CA. Diseases of the blood. In. Edwards CRW, Bouchier, IAD, Haslett, C, ed. Davidsons Principles and Practice of Medicine. Philadelphia: Churchill Livingstone; 1996: 808-812.







[xiv] Stanford Comprehensive Cancer Center. Information about Blood Diseases: Bone Marrow Transplantation. 2006. Available at: http://cancer.stanford.edu/blood/leukemias/bmt/ Accessed May 9, 2007.







[xv] Mackie MJ, Ludlam CA. Diseases of the blood. In. Edwards CRW, Bouchier, IAD, Haslett, C, ed. Davidsons Principles and Practice of Medicine. Philadelphia: Churchill Livingstone; 1996: 808-812.







[xvi] Stanford Comprehensive Cancer Center. Information about Blood Diseases: Bone Marrow Transplantation. 2006. Available at: http://cancer.stanford.edu/blood/leukemias/bmt/ Accessed May 9, 2007.







[xvii] Mackie MJ, Ludlam CA. Diseases of the blood. In. Edwards CRW, Bouchier, IAD, Haslett, C, ed. Davidsons Principles and Practice of Medicine. Philadelphia: Churchill Livingstone; 1996: 808-812.







[xviii] Mackie MJ, Ludlam CA. Diseases of the blood. In. Edwards CRW, Bouchier, IAD, Haslett, C, ed. Davidsons Principles and Practice of Medicine. Philadelphia: Churchill Livingstone; 1996: 808-812.







[xix] Mackie MJ, Ludlam CA. Diseases of the blood. In. Edwards CRW, Bouchier, IAD, Haslett, C, ed. Davidsons Principles and Practice of Medicine. Philadelphia: Churchill Livingstone; 1996: 808-812.










[xx] Mackie MJ, Ludlam CA. Diseases of the blood. In. Edwards CRW, Bouchier, IAD, Haslett, C, ed. Davidsons Principles and Practice of Medicine. Philadelphia: Churchill Livingstone; 1996: 808-812.







[xxi] Gottlieb, S. Bone marrow transplants show no benefit for non-Hodgkins lymphoma. BMJ. 2001; 322: 127. http://www.bmj.com/cgi/content/full/322/7279/127/a







[xxii] Gottlieb, S. Bone marrow transplants show no benefit for non-Hodgkins lymphoma. BMJ. 2001; 322: 127. http://www.bmj.com/cgi/content/full/322/7279/127/a







[xxiii] Curtis RE, Rowlings, PA, Deeg, HJ. Solid Cancers after Bone Marrow Transplantation. NEJM. 1997; 336:897-904. http://content.nejm.org/cgi/content/abstract/336/13/897







[xxiv] Perry K. Some children facing bone marrow transplant risk. Medical News Today. 2005. Available at: http://www.medicalnewstoday.com/medicalnews.php?newsid=29886 Accessed May 9, 2007.







[xxv] Merck. Hematopoietic Stem Cell Transplantation. 2005. Available at: http://www.merck.com/mmpe/sec13/ch166/ch166d.html Accessed May 9, 2007.

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