Research on Systemic Lupus Erythematosus - Book Report/Review Example

? Research Review on Systemic Lupus Erythematosus Teacher               Research Review on Systemic Lupus Erythematosus Study Hypothesis Based on previous studies with systemic lupus erythematosus, or SLE, the disease is believed to be treated using drugs that suppress the immune system. However, other patients with SLE do not respond to such a treatment and that such a treatment would be insufficient to control the disease. Therefore, what is important is to find out if certain specific methods work best with patients who are severely suffering from the disease or those who do not respond to current strategies and medication. These specific methods include intense immunosuppression as well as the use of autologous hematopoietic stem cell support (Burt et al., 2006). Population A closed cohort population was utilized in the study. The 50 patients enrolled in the study had a characteristic SLE that did not respond to conventional or standard immunosuppressive therapy. Moreover, these patients had visceral involvement that threatened either a vital organ or their very lives. The single-arm trial of 50 patients were enrolled from April 1997 to January 2005 in a study where they had to undergo autologous nonmyeloablative hematopoietic stem cell transplantation, or HSCT, in one US medical center (Burt et al., 2006). Study Design Although the design of the study is not clearly specified, it is obvious that what is utilized in the study is both an experimental and an observational approach. The study is a single-arm trial of 50 patients who had a treatment-refractory form of systemic lupus therapies as well as an impairment in the visceral area for other organs. The patients were actually enrolled in the program from April 1997 to January 2005, and thus had to undergo not only intense medication therapy but also an autologous nonmyeloablative hematopoietic stem cell transplantation or HSCT (Burt et al., 2006). The Timing of the Observations The study is a longitudinal study that observed and documented data from patients with treatment-refractory SLE from April 1997 through January 2005 for a period of nine years. Among those that served as primary data which were measured first were overall survival and disease remission. Secondary data which were measured immediately upon admission into the experimental study included the Systemic Lupus Erythematosus Disease Activity Index, or SLEDAI, the lupus serology test results as determined by the antinuclear antibody and anti-double-stranded DNA antibody, the test on complement C3 and C4, and the test on end-organ function determined by creatinine clearance, and the carbon monoxide diffusion lung capacity. Immunofluorescence was used to measure the determinants of the lupus serology tests (Burt et al., 2006). The study is also a longitudinal study because of the daily administrations of drugs that helped initiate leukapheresis. The mobilization of peripheral blood stem cells were triggered by the administration of cyclosphamide at 2.0g/m2 as well as the granulocyte colony-stimulating factor, or G-CSF, at 5 µg/kg per day. Both drugs were administered cutaneously 3 days after the study began (Burt et al., 2006). After the initial mobilization of the peripheral blood stem cells and 14 days after stem cell apheresis, the conditioning regimen was administered and consisted of 50 mg/kg daily administration of intravenous cyclosphamide and 30 mg/kg daily administration of intravenous equine ATG. The total of 200 mg/kg of intravenous cyclosphamide was given 5, 4, 3 and 3 days before transplantation, while the total of 90 mg/kg of intravenous equine ATG was given 4, 3 and 2 days before transplantation (Burt et al., 2006). Another reason why the study was a longitudinal study was that there was antibiotic prophylaxis or an antibiotic regimen that was required before patients had to undergo stem cell transplantation. This antibiotic regimen consisted of HSCT aerosolized pentamidine (300 mg/daily), fluoroquinolone in the form of levofloxacin and ciprofloxacin but changed to intravenous cefepime on the occurrence of neutropenia (daily), ambisome or voriconazole (daily), and acyclovir or valacyclovir (daily). Moreover, there were also injections of G-CSF (5 µg/kg daily) from the day of stem cell infusion and went on until the resolution of neutropenia, or where the absolute neutrophil count exceeds 1000 per microliter. Aside from those mentioned, patients also underwent a monthly administration of sulfamethoxazole/trimethoprim or pentamidine (3 times per week), fluoconazole or voriconazole (daily for 6 months), and acyclovir or valacyclovir after transplantation (twice a day for 1 year) (Burt et al., 2006). Aside from such medications, there are also those used as anticoagulation prophylaxis. These medications include subcutaneous enoxaparin (1.0 mg/kg every 12 hours) or subcutaneous dalteparin (200 U/kg daily) (Burt et al., 2006). There was also a follow-up conducted after 6 and 12 months and then every year thereafter. The patients were scheduled for follow-up and were checked for their current medical history, physical examination, imaging studies and serologic testing (Burt et al., 2006). All these medications indicate that the study was of the longitudinal type because they had to be administered for a relatively long time – in a matter of months and years. Moreover, the fact that there was a follow-up conducted for the patients even after the course of the study also proves that the study is of the longitudinal type. Relevant Etiologic Time Window Based on what was already known prior to the study, systemic lupus erythematosus, or SLE, is an autoimmune disease and was generally fatal before immunosuppressive medications were introduced in the market. Nevertheless, despite the advances in treatment such as the introduction of aggressive immunosuppressive medical therapies, some patients still have significantly high morbidity and mortality from SLE and would involve visceral organ problems associated with the disease. For these patients, whose SLE is treatment-refractory, what was recommended was “nonmyeloablative hematopoietic stem cell transplantation, or HSCT, regimen” (Burt et al., 2006). Based on previous studies and research and on what was previously known through theory, HSCT is a 2-step medical procedure. The first step is the administration of a conditioning regimen in order to eliminate lymphocytes that are self-reactive. The second step is the transplantation or infusion of the autologous hematopoietic stem cells. These autologous CD34-enriched hematopoietic stem cells are infused into the patient’s body as supportive blood product for the purpose of shortening the interval of conditioning regimen-related neutropenia. On the whole, HSCT is known as a form of “salvage” therapy specifically designed to treat refractory diseases especially after exhaustion of all available drug treatments. Some refractory diseases for which HSCT is being used include leukemia, Non-Hodgkin lymphoma, severe aplastic anemia, sickle cell disease, Wiskott-Aldrich syndrome, Hurler syndrome, Hunter disease, osteoporosis, Gaucher syndrome, and many other malignant diseases (Saria & Gosselin-Acomb, 2007). Because of the known effectiveness of HSCT in treating these diseases, Burt et al. (2006) decided to try the same thing on those with SLE. Research Study Base The study by Burt et al. in 2006 was based on previous studies on the effectiveness of the HSCT method of therapy. According to Burt et al. (2006), a European analysis made up of data from 53 patients in 23 centers reported that patients with SLE undergoing autologous HSCT as well as condition regimens increased their disease-free survival rate to 55%. This is somehow similar to the actual results of the study, which yielded 50%. Moreover, when it comes to the effectiveness of HSCT, there is a center effect on survival when it comes to malignancies. HSCT is effective against patients with various symptoms. As indicated in previous studies, if organ dysfunction is a contraindication for transplantation, then the most highly recommended method for treatment is stem cell transplantation, as in SLE. In patients with SLE, equine ATG was added to the conditioning regimen in order to promote further immunosuppression. Specifically, in SLE, the side effects of equine ATG include a syndrome that somehow mimics the active disease (SLE), and this manifestation includes symptoms like rash, fever, myalgias, hypotension, anthralgias, and shortness of breath. In order to counter these symptoms that mimic SLE and which have been brought about by equine ATG, what is usually administered is long-term, high-dose corticosteroids (Burt et al., 2006). The SLEDAI and RIFLE, which were the standard systems used for measuring the progress of the disease, have been used in previous studies and cases of SLE. Systemic lupus erythematosus utilizes SLEDAI and RIFLE because of the fact that the disease is a heterogeneous disease when it comes to its clinical course and manifestations. Through the results of various studies and actual clinical situations, the SLEDAI and RIFLE standard measures were appropriate for any disease that is being treated with HSCT. In fact, HSCT is appropriately measured by SLEDAI because HSCT indicates a significant improvement in the SLEDAI and even a 50% probability of 5-year remission is indicated in the standard measure (Burt et al., 2006). Population Sampling The total number of patients used in the experimental study was 50. All 50 patients were enrolled in the trial. However, only 48 patients decided to undergo HSCT therapy, because the two other patients died prior to the transplantation – one died from cerebral/pulmonary mucormycosis, and the second dying from active SLE. All these 50 patients were taken from the Northwestern Memorial Hospital at Chicago, Illinois, and they were considered qualified for the experimental study mainly because of their medication history. Twenty-one of t hem were under antihypertensive medication because they had a history of lupus nephritis. Other patients randomly suffered from the following symptoms: psychosis, seizures, headache, paraparesis, aseptic meningitis, transient ischemic attacks, hallucinations, transverse myelitis, and focal deficits. Other patients had immunomediated cytopenias that included disease-related pancytopenia, neutropenia, autoimmune hemolytic anemia or AIHA, and idiopathic thrombocytopenic purpura or ITP. The bottom line, however, was that all the patients had SLE refractory disease, which was the main focus of the study (Burt et al., 2006). The major criteria of patient eligibility for the chosen sample used for the study was a disease of the lungs such as alveolar hemorrhage, vasculitis and pneumonitis; a disease of the central nervous system such as transverse myelitis or cerebritis; a class III or IV glumerulonephritis, myositis and vasculitis, both confirmed by biopsy; antiphospholipid syndrome or APS; ulcerative mucocutaneous disease, hemodynamic compromise, severe serositis with effusions that lead to shortness of breath, and chronic and disabling pain. Overall, confirmation of patient eligibility was made possible by rheumatologists, pulmonologists, nephrologists and the transplantation physicians (Burt et al., 2006). Data Type Both secondary data and primary data were utilized in the study. Before the administration of HSCT and before transplantation, secondary data was utilized in order to determine the eligibility of the patient for the study. The patient’s pretransplantation medical history served as the only secondary data used in the study. Secondary data regarding the patients included data on the diseases affecting their central nervous system, lungs, and blood. Such secondary data refer to the presence of seizures, paraparesis, aseptic meningitis, headache, psychosis, focal deficits, hallucinations, transverse myelitis or transient ischemic attacks. Other secondary data refer to the presence of cytopenias such as autoimmune hemolytic anemia or AIHA, neutropenia, pancytopenia, or idiopathic thrombocytopenic purpura or ITP (Burt et al., 2006). Moreover, the secondary data in this study refer to other diseases that would confirm patient eligibility for the study. Such diseases include WHO class III or IV glumerulonephritis; central nervous system diseases like transverse myelitis or cerebritis; lung diseases like pneumonitis, vasculitis or hemorrhage of the alveoli; myositis or vasculitis confirmed by biopsy; antiphospholipid syndrome or APS; ulcerative mucocutaneous disease; or nephritis. Such secondary data have been taken from the previous medical records of the patients and have been confirmed through actual tests by nephrologists, transplantation physicians, rheumatologists, and pulmonologists (Burt et al., 2006). On the other hand, primary data in the study included the data taken through standard measures for the HSCT method of therapy. All the primary data taken in the study defined the effectiveness of HSCT in term of how it fulfills its goal of overall and disease-free survival. The data regarding probability of survival and relapse in lupus patients undergoing HSCT is defined as the state where the patient does not require any immunosuppressive medications except certain small doses of prednisone or hydroxychloroquine (Burt et al., 2006). When it comes to disease activity and organ function, the scores of the patients on the SLEDAI, which is a standard or validated instrument that measures significant improvement of any disease after HSCT was employed on the patient. In this particular study, the significant improvement of the patient from the disease includes the fact that the improvement of the life of the patient regardless of the presence of supplemental oxygen (Burt et al., 2006). Another type of primary data used in the study is the creatinine clearance, which was used to determine renal function. If the posttreatment creatinine clearance usually remains stable or has improved, this is a sign that HSCT is relatively good, and that is important when it comes to the treatment of SLE in general and the management of renal function problems in particular. Moreover, another standard test used in order to measure lung problem improvements was the Carbon Monoxide Diffusion Lung Capacity or DLCO (Burt et al., 2006). Another standard used in the study is serology and complement, consisting of the Antinuclear antibody, anti-ds DNA antibody tests as well as complement. These tests were done in order to ascertain whether stem cell transplantation was indeed effective in the alleviation of the symptoms of SLE and of its actual cure (Burt et al., 2006). Anticoagulation tests were also used to gather data on the levels of anticardiolipin antibodies as well as well as the levels of lupus anticoagulant. If these aforementioned levels have improved or normalized after the patient has undergone HSCT. Moreover, just like in the study, anticoagulation tests measured the severity of the symptoms of patients with SLE. Patients with SLE have experienced an improvement in the situation after the elimination of the anticoagulant through HSCT: a general improvement in the patient’s well being, the lessening of the severity of thromboembolic anticoagulation, and the elimination of risks from serious bleeding just because the anticoagulant is eliminated (Burt et al.). Statistical Data Both descriptive statistics and inferential statistics were used in the research study. Descriptive statistics was used in the presentation of secondary and primary evidence after they were found and confirmed. The secondary data on the medical history of the patients were presented through tables. These two tables are entitled “Patient Demographics and Pretransplantation History” and “Pretransplantation Disease Manifestations” (Burt et al., 2006). Through such form of descriptive statistics, the medical history of the patients was particularly exposed. Descriptive statistics was also employed by the researchers on the child victim in order to present primary data. Among those presented through tables included the toxic effects of transplantation, and the renal outcome of the patients. Similarly, those presented through figures included the probability of survival and relapse in lupus, specifically in patients who underwent HSCT; the changes in the serology and complement before and after HSCT; and data for the SLEDAI and DLCO measures, before and after HSCT (Burt et al., 2006). Conclusion Based on the results of the experimental study, conclusions have been formulated, and since most of these conclusions have been backed by experimental data and statistical significance, then most of them are valid. First, the researchers have concluded that HSCT was effective in the treatment of SLE and in the alleviation of its symptoms, with its probability of disease-free survival rate at 55% for five years based on a European analysis and 50% based on this actual study. Since the two data turned out to be very similar, then the conclusion on the effectiveness of the HSCT method in increasing disease-free survival rate among SLE patients is valid (Burt et al., 2006). I agree with this conclusion since this was somehow practically formulated through direct comparison with existing results taken from a previously conducted research study. However, the problem is that even survivors of HSCT may experience some delayed complication like chronic or prolonged neutropenia, or GVHD, which can actually be serious and may further cause bronchiolitis, cholestasis, esophageal stricture, or malabsorption (Copelan, 2006). The patient and the physician should therefore watch out for these diseases. The researchers have also concluded that high-dose chemotherapy and autologous HSCT were two effective ways to deal with severely ill SLE patients (Burt et al., 2006). I somehow agree with this conclusion because this is heavily backed with experimental evidence from the actual study. Chemotherapy alone would never work and neither would autologous HSCT alone. The combination of drugs and stem cell transplantation among patients with SLE is the method that yielded a relatively very high probability of disease-free survival rate of 50% in the study. Nevertheless, the researchers should have considered the idea that HSCT brings with it respiratory complications and even one-third of the population needing intensive care support (Saria & Gosselin-Acomb, 2007). Thus, this has to be taken into consideration. The researchers have also concluded that patients with cancer usually have chronic immunosuppression and infections, thus there is a need for aggressive preemptive antimicrobial prophylaxis for these patients (Burt et al., 2006). This has also been one of the significant findings in this study and this has been specifically underlined by the researchers. This somehow also implies that when it comes to any treatment, whether it be for SLE or for something else, it remains a fact that patients with cancer need to have a relatively much more aggressive regimen of drugs. The researchers have also concluded that the immunosuppressive conditioning regimen should use cyclosphamide, a standard lupus medication as well as the addition of equine ATG for further immunosuppression (Burt et al., 2006). Somehow, I agree with this because although treatment in the study involved HSCT, which is a general method for malignant diseases, it has to be specific to the disease itself which is being dealt with. In the case of SLE, the use of cyclosphamide and equine ATG are specific to the disease and therefore they work really well with other drugs used as well as HSCT. References Burt, R. K., Traynor, A., Statkute, L., Barr, W. G., Rosa, R., Schroeder, J., Verda, L., Krosnjar, N., Quigley, K., Yaung, K., Villa, M., Takahashi, M., Jovanovic, B. & Oyama, Y. (2006). Nonmyeoloablative Hematopoietic Stem Cell Transplantation for Systemic Lupus Erythematosus. Journal of the American Medical Association, 295(5), 527-535. Retrieved from JAMA: http://jama.jamanetwork.com/article.aspx?articleid=202293 Copelan, E. A. (2006). Hematopoietic Stem-Cell Transplantation. New England Journal of Medicine, 354, 1813-1826. Saria, M. G. & Gosselin-Acomb, T. K. (2007). Hemtopoietic Stem Cell Transplantation: Implications for Critical Care Nurses. Clinical Journal of Oncology Nursing, 11(1), 53-63. Read More