| Lucy Burns RN, BA, GradDip Applied Science (Nursing), Oncology Cert, MRCNA Clinical Nurse Specialist, Haematology 1 Stem Cell Transplant Unit, St Vincent's Hospital |
Traditionally, bone marrow transplantation, and more recently stem cell transplantation, has been limited as a treatment because of the risks associated with administering high doses of chemotherapy. Allogenic transplants continue to be associated with a morbidity and mortality of > 15%. Autologous transplantation, on the other hand, as a result of advances in the use of peripherally collected cells instead of bone marrow, prophylactic antimicrobials, and heparin, has an associated morbidity and mortality at St Vincent's of less than 1%. This has cleared the way for autologous transplantation to be used for the first time for non-malignant diseases, one of which is Rheumatoid Arthritis.
At St Vincent's, a trial of high dose Cyclophosphamide followed by autologous transplantation is in progress on a group of Rheumatoid Arthritis patients. For nurses, these patients present a new challenge as they are an unknown quantity. They have had little experience of hospitalisation and chemotherapy, with all its inherent risks and side-effects, and it is unknown what their preconceptions of the whole transplant process are.
On Cahill 19, we intend to carry out research looking at these preconceptions and how they compare with the actual experience of transplantation. The information gathered will assist in the setting up of an improved pretransplant education program and help us lessen the stress of the transplant, both for these patents and the others who will surely follow.
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St Vincent's Hospital, Sydney, carried out Australia's first Bone Marrow Transplant in 1975. At the time it was a strictly experimental procedure. The patient, a woman in her early thirties with Acute Myloid Leukaemia, was offered a transplant as a final attempt to interrupt the progression of her disease. She had not been able to achieve any sort of remission using what was then, conventional treatment. Unfortunately, it was not successful, and she died two weeks post transplant from disseminated candida.
In the intervening 23 years, many advances have been made. Bone marrow or stem cell transplantation which involves the administration of lethal doses of chemotherapy plus or minus radiotherapy, followed by rescue with hopefully 'clean' or disease free cells, was once seen as a high risk procedure to be attempted only on patients with terminal haematological illnesses whose options had been exhausted. It is now a viable treatment for a variety of diseases, including for the first time specific non life-threatening but none the less debilitating illnesses such as Rheumatoid Arthritis (RA). This paper will briefly examine the recent developments that have enabled the next step in stem cell transplantation to be taken. All references to St Vincent's Hospital are to be taken as referring to St Vincent's General Hospital, Sydney.
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In the beginning, bone marrow transplants were performed mainly for the haematological diseases such as the leukaemias, lymphomas, aplastic anaemia and myeloma and usually when these diseases were at an advanced stage. As clinical results improved, it became more ethically acceptable to undertake transplantation earlier in the course of disease, and then for other serious, though not immediately fatal diseases such as thalassaemia major and sickle cell disease. (Thomas, 1997).
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While the haematological diseases continue to account for a significant proportion of stem cell transplants performed, other forms of cancer have been treated with varying degrees of success. Transplantation has been both allogeneic, that is those in which the donor is someone other than oneself, usually a sibling, and more commonly, autologous stem cell transplantation, where one receives back one's own 'clean' cells.
Breast cancer is becoming one of the more common indications for treatment with an autologous stem cell transplant. It has been the primary indication for stem cell transplantation in the United States for the last two years although still technically classed as an experimental procedure there, and in 1996 was the predominant disease type treated at St Vincent's Hospital. Transplants are currently performed here on pre-menopausal women with 10 or more involved lymph nodes and preferably without metastases. Results have shown a 72% 4-year survival probability for high risk patients and a 45% 4-year survival probability for those with metastatic disease (Nivison-Smith & Hawkins, 1996).
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The main limit to the use of stem cell transplantation has been the risk associated with administering high dose chemotherapy. Transplants continue to be associated with a morbidity and mortality of >15%. Autologous transplants, on the other hand, as a result of developments such as the use of peripherally collected cells rather than bone marrow and prophylactic antimicrobials and heparin (Atkinson et al., 1995), have an associated morbidity and mortality of less than 1%. In fact, St Vincent's Hospital has not had an autologous transplant associated death since August 1992. Between that time and February 1998, 123 people have received this therapeutic treatment.
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Autoimmune disease arises as a consequence of disturbed and altered immune responses leading to an attack by the immune system against host antigens (Tyndall & Gratwohl, 1997). While the mechanisms of the disease process are still poorly understood, once established, it generally leads to widespread tissue destruction and sometimes death.
Over the years, there has been much clinical evidence that allogeneic transplantation can provide an extended remission period and eventually a cure for various autoimmune diseases. This outcome was discovered when a patient was being treated for aplastic anaemia which had developed as a result of pharmacological treatment for Rheumatoid Arthritis. There have also been documented cases of remission of a co-existing autoimmune disease following autologous transplantation (Snowden et al., 1996). Animal studies have provided support for these clinical findings. (Marmont & Van Bekkum, 1995; Hamilton et al., 1995; Tyndall & Gratwohl, 1995).
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Rheumatoid arthritis is a systemic autoimmune disease of unknown aetiology which causes significant morbidity. Symptoms include chronic inflammation of the synovial lining of the joints, most commonly the wrists, metacarpophalangeal joints of the hands and the metatarsophalangeal joints of the feet. Extra articular involvement includes muscle atrophy, anaemia, osteoporosis and skin, ocular, vascular, pulmonary and cardiac symptoms. The majority of patients who have the disease more than 12 months will continue to have exacerbations for the rest of their lives, and up to 50% will be unable to work within 10 years of contracting the disease (Snowden et al., 1997).
The limited success of current therapies for people with RA has led to a change in management with a more aggressive approach now being taken. Autologous transplantation now is, as mentioned above, a relatively safe procedure and is part of that aggressive approach.
In 1997, St Vincent's Hospital became the first hospital in the world to commence trialling the use of high dose Cyclophosphamide followed by autologous peripheral stem cell transplantation on a group of RA patients.
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The transplant environment is less intimidating than it was in the past. The remarkable improvement in morbidity and mortality figures at St Vincent's have been achieved using a minimalist isolation policy in contrast to many other institutions around the world. Nursing research carried out at St Vincent's Hospital led to the discarding of the gowns, masks and closed doors that had been part of the process for so long, and the current policy consists simply of handwashing prior to entering and immediately upon leaving each patient's room or bedside and otherwise adhering to routine Body Substance Isolation practices.
Transplant patients are nursed in single rooms but they are not restricted to these rooms. In fact, they are encouraged to get out of their rooms and in and out of the hospital as often as they are able. We place no restrictions on what food they can eat, the number of visitors they have, or the presence of flowers in their rooms. We tell our patients that they themselves are the best judges of what they can and cannot do. We merely encourage them to be sensible and to trust in their own instincts.
While we have been able to create a better patient environment and the various prophylaxes used prevent or alleviate some of the side effects of the treatment, it is certainly not all plain sailing. The transplant process is always a challenging time for patients. As a result of the chemotherapy, they become profoundly neutropenic, leaving them prone to sepsis, with subsequent treatment with intravenous antibiotics. They are anaemic and thrombocytopenic, requiring transfusions of blood and platelets. These interventions entail risks of their own.
The patient experiences painful mucositis and oesophagitis, nausea, vomiting and diarrhoea. The potential to develop haemorrhagic cystitis means the patient must be attached to intravenous hydration continuously for five days, restricting their movements and disrupting their sleep. The transplant patient must also deal with alterations in body image related to the chemotherapy induced alopecia, the issue of sterility and ultimately the risk, albeit small, of mortality. In addition to all this, the RA patient is already suffering from the considerable pain and debilitation associated with that disease.
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From a nursing point of view, these patients present a particular challenge as they, unlike the 'average' transplant patient, have little or no experience of hospitalisation. Although they may have been treated with low dose Methotrexate in the past, they have no experience of high dose chemotherapy with all its inherent risks and side effects. In addition, we, the nurses on the ward, have very little knowledge of the specific needs of the patient with RA. What we and the patients do know, is that this is an experimental procedure with no guarantee of success, although some of the initial results are promising.
As for all that we do not know, a nursing research team will be carrying out research in 1998, with the aim of combating that knowledge deficit. Patients admitted to the unit for a transplant for RA will be asked what their preconceptions of the transplant process are, and these preconceptions will be compared to the reality of the patient's experience following the transplant.
The information gathered will be used to improve pretransplant education, and the management of specific symptoms and the patients' associated worries and concerns. Rheumatoid arthritis is only the beginning. The potential exists for autologous transplantation to be used for an increasingly broader variety of illnesses. Possible future trials will involve people with systemic lupus erythematosis and, in the United States, multiple sclerosis. The nursing research team believes that the research we are about to undertake is important not only in that it will improve our knowledge, but also because it is part of our duty of care to our patients with RA and to those that may follow them to provide them with the least traumatic transplant experience possible.
Stem cell transplantation in Australia has come a long way in just 23 years. It has developed from an experimental procedure with limited application, to a much safer and more viable treatment for many diseases. St Vincent's Hospital performed eight stem cell transplants on patients with RA in 1997. The results are now being evaluated, and further trials will be carried out this year. We have now taken the next step and who knows what may be possible in the future.
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