Jung, Ki Hwan;Sung, Hwa Jung;Lee, Ju-Han;Han, Jungho;Shin, Chol;Park, Hyung Joo;Kim, Je Hyeong
Tuberculosis and Respiratory Diseases
/
v.66
no.2
/
pp.122-126
/
2009
Despite the improvements in supportive care, early and late hematopoietic stem cell transplantation-related complications still remain a significant cause of morbidity and mortality. Pulmonary complications occur in 40-60% of patients who undergo allogeneic hematopoietic stem cell transplantation. Late-onset noninfectious pulmonary complications can occur months and even years after transplantation. Interstital lung disease has also been reported to be a late post-transplant complication. Exposure to cytotoxic drugs and/or irradiation has been implicated as a cause of pulmonary toxicity including pulmonary fibrosis. We report a case of an 18-year-old female with non-classifiable interstitial pneumonia that manifested eight and a half years after allogeneic hematopoietic stem cell transplantation. The condition worsened rapidly and the patient eventually died.
Mesenchymal stem cells (MSCs) are effective in treating autoimmune diseases and managing various conditions, such as engraftment of allogeneic islets. Additionally, autologous and HLA-matched allogeneic MSCs can aid in the engraftment of human allogeneic kidneys with or without low doses of tacrolimus, respectively. However, HLA alloantigens are problematic because cell therapy uses more HLA-mismatched allogeneic cells than autologous for convenience and standardization. In particular, HLA-mismatched MSCs showed increased Ag-specific T/B cells and reduced viability faster than HLA-matched MSCs. In CRISPR/Cas9-based cell therapy, Cas9 induce T cell activation in the recipient's immune system. Interestingly, despite their immunogenicity being limited to the cells with foreign Ags, the accumulation of HLA alloantigen-sensitized T/B cells may lead to allograft rejection, suggesting that alloantigens may have a greater scope of adverse effects than foreign Ags. To avoid alloantigen recognition, the β2-microglobulin knockout (B2MKO) system, eliminating class-I MHC, was able to avoid rejection by alloreactive CD8 T cells compared to controls. Moreover, universal donor cells in which both B2M and Class II MHC transactivator (CIITA) were knocked out was more effective in avoiding immune rejection than single KO. However, B2MKO and CIITA KO system remain to be controlled and validated for adverse effects such as the development of tumorigenicity due to deficient Ag recognition by CD8 T and CD4 T cells, respectively. Overall, better HLA-matching or depletion of HLA alloantigens prior to cell therapy can reduce repetitive transplantation through the long-term survival of allogeneic cell therapy, which may be especially important for patients seeking allogeneic transplantation.
CTLA-4Ig is regarded as an inhibitory agent of the T cell proliferation via blocking the costimulatory signal which is essential for full T cell activation. To improve applicability, we developed the CTLA-4Ig-CTKC in which the c-terminal lysine had been replaced by cysteine through single amino acid change. The single amino acid mutation of c-terminus of CTLA-4Ig was performed by PCR and was checked by in vitro transcription and translation. DNA construct of mutant form was transfected to Chinese hamster ovary (CHO) cells by electroporation. The purified proteins were confirmed by Western blot and B7-1 binding assay for their binding ability. The suppressive capacity of CTLA-4Ig-CTKC was evaluated by the mixed lymphocyte reaction (MLR) and in the allogeneic pancreatic islet transplantation model. CTLA-4Ig-CTKC maintained binding ability to B7-1 molecule and effectively inhibits T cell proliferation in MLR. In the murine allogeneic pancreatic islet transplantation, short-term treatment of CTLA-4Ig-CTKC prolonged the graft survival over 100 days. CTLA-4Ig-CTKC effectively inhibits immune response both in MLR and in allogeneic islet transplantation model, indicating that single amino acid mutation does not affect the inhibitory function of CTLA-4Ig. CTLA-4Ig-CTKC can be used in vehicle-mediated drug delivery system such as liposome conjugation.
Chronic graft-versus-host disease (GVHD) is a well-known complication of allogeneic bone marrow transplantation (BMT) and has heterogeneous manifestations, with multi-organ involvement. Recently, polymyositis (PM) was reported to be a rare manifestation of chronic GVHD. Here, we report a 30-year-old woman who was diagnosed with PM after allogeneic BMT.
Hemorrhagic cystitis (HC) is a common complication after allogeneic transplantation. Early posttransplant HC occurs in association with cyclophosphamide, while later on HC results from viral infections such as polyomavirus BK (BKV) and adenovirus. We report here the case of a 57-year-old woman who received an instillation of cidofovir into the bladder for the treatment of hemorrhagic cystitis after allogeneic peripheral stem cell transplantation for her acute myeloid leukemia. Cyclophosphamide and busulfan were used as conditioning treatments. Cyclosporin was administered daily. On the 71st day after transplantation, the patient developed acute severe hemorrhagic cystitis, and BK virus was demonstrated in the urine samples using polymerase chain reaction. Her urinary symptoms did not improve in spite of palliative treatment, but a response was evident after intravesical cidofovir treatment.
Acute graft-versus-host-disease (GVHD) is characterized by selective damage to the liver, the skin, and the gastrointestinal tract. Following allogeneic hematopoietic stem cell transplantation, donor bone marrow (BM) cells repopulate the immune system of the recipient. We previously demonstrated that the acute intestinal GVHD (iGVHD) mortality rate was higher in MyD88-deficient BM recipients than that in the control BM recipients. In the present study, the role of MyD88 (expressed by donor BM) in the pathophysiology of hepatic GVHD (hGVHD) was examined. Unlike iGVHD, transplantation with MyD88-deficient T-cell depleted (TCD) BM attenuated hGVHD severity and was associated with low infiltration of T cells into the liver of the recipients. Moreover, GVHD hosts, transplanted with MyD88-deficient TCD BM, exhibited markedly reduced expansion of $CD11b^+Gr-1^+$ myeloidderived suppressor cells (MDSC) in the liver. Adoptive injection of the MDSC from wild type mice, but not MyD88-deficient mice, enhanced hepatic T cell infiltration in the MyD88-deficient TCD BM recipients. Pre-treatment of BM donors with LPS increased MDSC levels in the liver of allogeneic wild type BM recipients. In conclusion, hGVHD and iGVHD may occur through various mechanisms based on the presence of MyD88 in the non-T cell compartment of the allograft.
In recent years, the mesenchymal stem cells (MSC) derived from various tissues have been widely tested for developing cell therapies, tissue repair and transplantation. Although there has been much interest in the immunomodulatory properties of MSC and their immunologic reactions following autologous, allogeneic and xenogenic transplantation of MSC in vivo, up to date, the expression of immunogenic markers, such as class I and II human leukocyte antigens (HLA), after differentiation of human umbilical cord blood (hUCB)-derived MSC has been poorly investigated and require extensive in vitro and in vivo testing. In this experiment, the expression of the HLA-ABC and HLA-DR on hUCB-derived MSC have been tested by immunocytochemical staining. The undifferentiated MSC were moderately stained for HLA-ABC but very weakly for HLA-DR. In order to investigate the inhibitory effect of allogeneic lymphocytes on proliferation of MSC, the MSC were cultured in the presence or absence of peripheral allogeneic lymphocytes stimulated with concanavalin A. The allogeneic lymphocytes did not significantly inhibit MSC proliferation. We conclude that hUCB-MSC expressed moderately class I HLA antigen while almost negatively class II HLA antigen. The MSC have an immunomodulatory effect which can suppress the allogeneic response of lymphocytes. These in vitro data suggest that allogeneic MSC derived from cord blood can be useful candidate for allogeneic cell therapy and transplantation without a major risk of rejection.
The purpose of this study was to develop a clinical pathway for the allogeneic bone marrow transplantation donor. For this study, a conceptual framework was developed through a review of the literature including six steps which are using in Jones Hopkins Hospital. USA. The researcher reviewed 129 medical re-cords of donor who had bone marrow donation between January 2002 to January 2004, to identify the overall service contents required by these patients and to make a preliminary clinical pathway. A content validity test was done for the preliminary clinical pathway, a professional group screened 51 medical re-cords and adopted with 3 hospitalization days as the clinical pathway framework. In the fifth step, clinical pathway test was also done to 7 donors from April 28th to July, 2004. After these processes the final clinical pathway was developed. The results of this study are as follows: 1. The vertical axis of the clinical pathway Includes the following 9 items: vital signs, nursing assessment, activity, diet, intervention, medication, test, consultation and patient teaching. The duration of the horizontal axis was 3days from admission to discharge 2. Analysis of the 129 medical records indicated that the average length of stay was 3 4 days. The medical performance according to the vertical axis in the preliminary clinical pathway consisted of 51 items After clinical validity test, it steel consisted of 51 items in the final form. 3. Clinical Validity test was done to 7 bone marrow donors. During these process, The first patient was deleted because he was out of the criteria the investigate set and 6 patients were used, finally The result of this study indicated all of 7 donors were discharged on expected day. 4. Clinical pathway enables to improve the quality of care, multidisciplinary team work It also helps nursing bone marrow donor, effective education to donor or medical member. The results of this study suggest that clinical pathway may be able to improve the quality of nursing care for bone marrow transplantation donors.
Purpose: To summarize and review the methodological quality of the evidence from trials examining the effectiveness of physical exercise in patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-HSCT). Methods: Six randomized clinical trials (RCTs) were identified, reviewed for substantive results, and assessed for methodological quality. Results: Six trials met all methodological criteria on the modified Jadad score above 3 out of 5 points. Failure to blind the outcome assessor, and failure to describe the method of blinding of outcome assessor appropriately were the most prevalent methodological shortcomings. Various exercise modalities have been applied, differing in content, frequency, intensity, and duration. Positive results have been observed in part for a diverse set of outcomes, including physical and psychological performance. Conclusion: The trials reviewed in this study were of moderate methodological quality. They suggest that exercise in patients undergoing Allo-HSCT may be safe and feasible, and in part patients benefit from increased physical performance both during and after transplantation. Future RCTs should use larger samples, appropriate comparison groups, and a standard of outcome measures, and examine what kind of exercise intervention (aerobic vs. resistance vs. combined) is the most effective for Allo-HSCT patients. It would be necessary to define contraindication for exercise to guarantee its safety.
Kim Nam-Cho;Kim Hee-Seung;Choi So-Eun;Park Hyun-Jeong
Journal of Korean Public Health Nursing
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v.14
no.2
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pp.191-202
/
2000
This study was conducted for 39 patients who are recipients of allogeneic hemopoietic stem cell transplantation at BMT ward of St. Mary's hospital affiliated to Catholic University of Korea from April to September 1999. The subjects were devided into two groups; those who received both TEl and chemo therapy as conditioning regimen (TEl group). and those who used chemo agents as singular conditioning regimen (chemo group). The oral intake status of the two groups were compared through physical assessment and blood chemistry exam of the subjects, and factors influencing their nutritional change and oral intake were explored in each stage of the transplantation (six stages: admission, conditional stage, date of transplantation, one week after transplantation, two weeks after transplantation, and three weeks after transplantation). The prior aim of the study was to provide baseline data to minimize delayed treatment from nutritional deficiency of the subjects. The results were as follows: 1. TBI group was significantly decreased of oral calorie intake in two weeks after transplantation compared to admission and conditioning stage while that of chemo group was significantly decreased on the date of transplantation. 2. TBI group was significantly decreased of protein intake in two weeks after transplantation compared to admission and conditioning stage. In chemo group, protein intake was significantly decreased on the date of transplantation compared to admission. It was remarkable that TBI group showed lesser protein intake than chemo group. 3. Both group were significantly decreased of BMI in one week and three weeks after transplantation compared to admission. TBI group showed significantly higher BMI than chemo group. 4. Both group were significantly decreased of Triceps Skinfold Thickness (TST)on the date of transplantation compared to admission stage. 5. TBI group was significantly decreased of mid-arm muscle circumference (MAMC) in two weeks after transplantation compared to admission, conditioning, date of transplantation. 6. TBI group was significantly decreased of albumin level in two weeks after transplantation compared admission stage. In chemo group, it was significantly decreased on the date of transplantation compared to admission, three weeks after the transplantation. 7. TBI group was significantly decreased of transferrin level in two weeks after transplantation compared admission, conditioning, date of transplantation and one week after transplantation. In chemo group, it was decreased of transferrin level in 3 weeks after transplantation. 8. Oral intake of TEl group was impacted by vomiting before transplantation and gingivitis after transplantation. In chemo group, it was impacted by vomiting before transplantation and by two factors, gingivitis and nausea, after transplantation. The results showed oral calorie intake was not different between the two groups while protein intake was significantly lower in TBI group than chemo group. Oral intake was significantly impacted by vomiting before transplantation in both groups, but affected by oral gingivitis in TBI group and gingivitis and nausea in chemo group after transplantation. This findings present that standardized strategies to manage nutrition and gingivitis more effectively are desperately needed to enhance oral intake and protein intake of patients who receive TBI as conditioning regimen.
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